Characterization of the complete chloroplast genome of Eutrema deltoideum (Brassicaceae).

Eutrema deltoideum (Hook. f. et Thoms.) has been recognized as a potentially important vegetable and medicinal resource. In this study, we present the complete chloroplast genome of E. deltoideum and conduct a phylogenetic analysis. The chloroplast genome is 154,051 bp long and consists of a large single-copy (LSC) region of 84,149 bp, two inverted repeat (IR) regions of 26,065 bp each, and a small single-copy (SSC) region of 17,772 bp. It contains 132 complete genes, including 87 protein-coding genes, 8 ribosomal RNA genes, and 37 tRNA genes. Additionally, we identified 78 simple sequence repeats (SSRs). The phylogenetic tree reveals that E. deltoideum is closely related to E. heterophyllum, and the Eutrema genus is monophyletic. This study provides valuable information about E. deltoideum and enhances our understanding of its taxonomic classification.

IRF4-BLOC1S5: the first rearrangement gene identified in TEMPI syndrome.

Not available.

Activating plant immunity: the hidden dance of intracellular Ca2+ stores.

Calcium ion (Ca2+) serves as a versatile and conserved second messenger in orchestrating immune responses. In plants, plasma membrane-localized Ca2+-permeable channels can be activated to induce Ca2+ influx from extracellular space to cytosol upon pathogen infection. Notably, different immune elicitors can induce dynamic Ca2+ signatures in the cytosol. During pattern-triggered immunity, there is a rapid and transient increase in cytosolic Ca2+, whereas in effector-triggered immunity, the elevation of cytosolic Ca2+ is strong and sustained. Numerous Ca2+ sensors are localized in the cytosol or different intracellular organelles, which are responsible for detecting and converting Ca2+ signals. In fact, Ca2+ signaling coordinated by cytosol and subcellular compartments plays a crucial role in activating plant immune responses. However, the complete Ca2+ signaling network in plant cells is still largely ambiguous. This review offers a comprehensive insight into the collaborative role of intracellular Ca2+ stores in shaping the Ca2+ signaling network during plant immunity, and several intriguing questions for future research are highlighted.

Visual Gustation via Regulable Elastic Photonic Crystals.

The unique structural sensitivity of photonic crystals (PCs) endows them with stretchable or elastic tunability for light propagation and spontaneous emission modulation. Hydrogel PCs have been demonstrated to have biocompatibility and flexibility for potential human health detection and environmental security monitoring. However, current elastic PCs still possess a fixed elastic modulus and uncontrollable structural colors based on a tunable elastic modulus, posing considerable challenges for in situ detection, particularly in wearable or portable sensing devices. In this work, we introduced a novel chemo-mechanical transduction mechanism embedded within a photonic crystal nanomatrix, leading to the creation of structural colors and giving rise to a visual gustation sensing experience. By utilizing the captivating structural colors generated by the hydrogel PC, we employ abundant optical information to identify various analytes. The finite element analysis proved the electric field distribution in the PC matrix during stretch operations. The elastic-optical behaviors with various chemical cosolvents, including cations, anions, saccharides, or organic acids, were investigated. The mechanism of the Hofmeister effect regulating the elasticity of hydrogels was demonstrated with the network nanostructure of the hydrogels. The hydrogel PC matrix demonstrates remarkable capability in efficiently distinguishing a wide range of cations, anions, saccharides, and organic acids across various concentrations, mixtures, and even real food samples, such as tastes and soups. Through comprehensive research, a precise relationship between the structural colors and the elastic modulus of hydrogel PCs has been established, contributing to the biomatching elastic-optics platform for wearable devices, a dynamic environment, and clinical or health monitoring auxiliary.

Screening oral drugs for their interactions with the intestinal transportome via porcine tissue explants and machine learning.

In vitro systems that accurately model in vivo conditions in the gastrointestinal tract may aid the development of oral drugs with greater bioavailability. Here we show that the interaction profiles between drugs and intestinal drug transporters can be obtained by modulating transporter expression in intact porcine tissue explants via the ultrasound-mediated delivery of small interfering RNAs and that the interaction profiles can be classified via a random forest model trained on the drug-transporter relationships. For 24 drugs with well-characterized drug-transporter interactions, the model achieved 100% concordance. For 28 clinical drugs and 22 investigational drugs, the model identified 58 unknown drug-transporter interactions, 7 of which (out of 8 tested) corresponded to drug-pharmacokinetic measurements in mice. We also validated the model's predictions for interactions between doxycycline and four drugs (warfarin, tacrolimus, digoxin and levetiracetam) through an ex vivo perfusion assay and the analysis of pharmacologic data from patients. Screening drugs for their interactions with the intestinal transportome via tissue explants and machine learning may help to expedite drug development and the evaluation of drug safety.

COVID-19 in immunocompromised patients after hematopoietic stem cell transplantation: a pilot study.

Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients at early stage of immune reconstitution after hematopoietic stem cell transplantation (HSCT) are limited. In the present study, we retrospectively investigated the incidence and clinical features of SARS-CoV-2 infection in patients who underwent HSCT in 2022. Patients (allo-HSCT, n = 80; auto-HSCT, n = 37) were consecutively included in the study. The SARS-CoV-2 infection rate was 59.8%, and the median interval of HSCT to coronavirus disease 2019 (COVID-19) was 4.8 (range: 0.5-12) months. Most patients were categorized as mild (41.4%) or moderate (38.6%), and 20% as severe/critical. No deaths were attributable to COVID-19. Further analysis showed that lower circulating CD8+ T-cell counts and calcineurin inhibitor administration increased the risk of SARS-CoV-2 infection. Exposure to rituximab significantly increased the probability of severe or critical COVID-19 compared with that of mild/moderate illness (P < .001). In the multivariate analysis, rituximab use was associated with severe COVID-19. Additionally, COVID-19 had no significant effect on immune reconstitution. Furthermore, it was found that Epstein-Barr virus infection and rituximab administration possibly increase the risk of developing severe illness. Our study provides preliminary insights into the effect of SARS-CoV-2 on immune reconstitution and the outcomes of allo-HSCT recipients.

Early T-cell reconstitution predicts risk of EBV reactivation after allogeneic hematopoietic stem cell transplantation.

The quality of immune reconstitution (IR) is crucial for the outcome of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and is closely connected with infection, relapse and graft-versus-host disease (GvHD) which are the most important causes for transplantation failure. However, the IR pattern in the early stage after allo-HSCT, particularly haploidentical (HID) HSCT, remains unclear. In this retrospective study, we examined the T cell reconstitution of patients within the initial 30 days (n = 173) and 100 days (n = 122) after allo-HSCT with myeloablative condition (MAC), of which > 70% were HID HSCT, to assess the influence of IR on the transplant outcomes. By comparing 78 patients with good IR (GIR) to 44 patients with poor IR (PIR), we observed that GIR was associated with lower risk for Epstein-Barr virus (EBV) reactivation and cytomegalovirus (CMV) reactivation, but had no significant impacts on the survival outcomes (i.e., overall survival, event-free survival) and cumulative incidences of GvHD. Importantly, we found lymphocyte reconstitution pattern at day 30 after allo-HSCT would be a surrogate for IR evaluated at day 100. In the Cox proportional hazard model, early reconstitution of CD4+, CD4+CD25+, CD4+CD45RO+, CD4+CD25+CD27low, and CD8+ T cells at day 30 was reversely correlated with risk of EBV reactivation. Finally, we constructed a predictive model for EBV reactivation with CD8+ and CD4+CD45RO+ T cell proportions of the training cohort (n = 102), which was validated with a validation cohort (n = 37). In summary, our study found that the quality of IR at day 30 had a predictive value for the risk of EBV reactivation, and might provide guidance for close monitoring for EBV reactivation.

Targeted mutagenesis of flavonoid biosynthesis pathway genes reveals functional divergence in seed coat colour, oil content and fatty acid composition in Brassica napus L.

Yellow-seed is widely accepted as a good-quality trait in Brassica crops. Previous studies have shown that the flavonoid biosynthesis pathway is essential for the development of seed colour, but its function in Brassica napus, an important oil crop, is poorly understood. To systematically explore the gene functions of the flavonoid biosynthesis pathway in rapeseed, several representative TRANSPARENT TESTA (TT) genes, including three structural genes (BnaTT7, BnaTT18, BnaTT10), two regulatory genes (BnaTT1, BnaTT2) and a transporter (BnaTT12), were selected for targeted mutation by CRISPR/Cas9 in the present study. Seed coat colour, lignin content, seed quality and yield-related traits were investigated in these Bnatt mutants together with Bnatt8 generated previously. These Bnatt mutants produced seeds with an elevated seed oil content and decreased pigment and lignin accumulation in the seed coat without any serious defects in the yield-related traits. In addition, the fatty acid (FA) composition was also altered to different degrees, i.e., decreased oleic acid and increased linoleic acid and α-linolenic acid, in all Bnatt mutants except Bnatt18. Furthermore, gene expression analysis revealed that most of BnaTT mutations resulted in the down-regulation of key genes related to flavonoid and lignin synthesis, and the up-regulation of key genes related to lipid synthesis and oil body formation, which may contribute to the phenotype. Collectively, our study generated valuable resources for breeding programs, and more importantly demonstrated the functional divergence and overlap of flavonoid biosynthesis pathway genes in seed coat colour, oil content and FA composition of rapeseed.

Diagnostic efficiency of metagenomic next-generation sequencing for suspected infection in allogeneic hematopoietic stem cell transplantation recipients.

Introduction: Immunosuppression predisposes allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients to infection. Prompt and accurate identification of pathogens is crucial to optimize treatment strategies. This multi-center retrospective study aimed to assess the ability of metagenomic next-generation sequencing (mNGS) to detect causative pathogens in febrile allo-HSCT recipients and examined its concordance with conventional microbiological tests (CMT). Methods: We performed mNGS and CMT on samples obtained from 153 patients with suspected infection during allo-HSCT. Patients were grouped based on their neutropenic status at the time of sampling. Results: The mNGS test was more sensitive than CMT (81.1% vs. 53.6%, P<0.001) for diagnosing clinically suspected infection, especially in the non-neutropenia cohort. mNGS could detect fungi and viruses better than bacteria, with a higher sensitivity than CMT. Immune events were diagnosed in 57.4% (35/61) of the febrile events with negative mNGS results, and 33.5% (48/143) with negative CMT results (P=0.002). The treatment success rate of the targeted anti-infection strategy was significantly higher when based on mNGS than on empirical antibiotics (85% vs. 56.5%, P=0.004). Conclusion: The mNGS test is superior to CMT for identifying clinically relevant pathogens, and provides valuable information for anti-infection strategies in allo-HSCT recipients. Additionally, attention should be paid to immune events in patients with negative mNGS results.

Angiopoietin-2 is associated with capillary leak and predicts complications after cardiac surgery.

BACKGROUND: Patients undergoing cardiac surgery are prone to numerous complications. Increased vascular permeability may be associated with morbidity and mortality due to hemodynamic instability, fluid overload, and edema formation. We hypothesized that markers of endothelial injury and inflammation are associated with capillary leak, ultimately increasing the risk of postoperative complications. METHODS: In this prospective, observational, multidisciplinary cohort study at our tertiary academic medical center, we recruited 405 cardiac surgery patients. Patients were assessed daily using body impedance electrical analysis, ultrasound, sublingual intravital microscopy, and analysis of serum biomarkers. Multivariable models, as well as machine learning, were used to study the association of angiopoietin-2 with extracellular water as well as common complications after cardiac surgery. RESULTS: The majority of patients underwent coronary artery bypass grafting, valvular, or aortic surgeries. Across the groups, extracellular water increased postoperatively (20 ± 6 preoperatively to 29 ± 7L on postoperative day 2; P < 0.001). Concomitantly, the levels of the biomarker angiopoietin-2 rose, showing a strong correlation based on the time points of measurements (r = 0.959, P = 0.041). Inflammatory (IL-6, IL-8, CRP) and endothelial biomarkers (VE-Cadherin, syndecan-1, ICAM-1) suggestive of capillary leak were increased. After controlling for common risk factors of edema formation, we found that an increase of 1 ng/mL in angiopoietin-2 was associated with a 0.24L increase in extracellular water (P < 0.001). Angiopoietin-2 showed increased odds for the development of acute kidney injury (OR 1.095 [95% CI 1.032, 1.169]; P = 0.004) and was furthermore associated with delayed extubation, longer time in the ICU, and a higher chance of prolonged dependence on vasoactive medication. Machine learning predicted postoperative complications when capillary leak was added to standard risk factors. CONCLUSIONS: Capillary leak and subsequent edema formation are relevant problems after cardiac surgery. Levels of angiopoietin-2 in combination with extracellular water show promising potential to predict postoperative complications after cardiac surgery. TRIAL REGISTRATION NUMBER: German Clinical Trials Registry (DRKS No. 00017057), Date of registration 05/04/2019, www.drks.de.

Efficacy and safety of the C5 inhibitor crovalimab in complement inhibitor-naive patients with PNH (COMMODORE 3): A multicenter, Phase 3, single-arm study.

The Phase 3 single-arm COMMODORE 3 study (ClinicalTrials.gov, NCT04654468) evaluated efficacy and safety of crovalimab (novel C5 inhibitor) in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria (PNH). COMMODORE 3 enrolled patients from five China centers. Eligible complement inhibitor-naive patients with PNH were ≥12 years old, had lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN), and had ≥4 transfusions of packed red blood cells within the prior 12 months. Patients received crovalimab loading doses (one intravenous, four subcutaneous) and subsequent every-4-weeks subcutaneous maintenance doses per weight-based tiered-dosing schedule. Co-primary efficacy endpoints were mean proportion of patients with hemolysis control (LDH ≤1.5 × ULN) from Week (W)5 through W25 and difference in proportion of patients with transfusion avoidance from baseline through W25 versus within 24 weeks of prescreening in patients who had ≥1 crovalimab dose and ≥1 central LDH assessment after first dose. Between March 17 and August 24, 2021, 51 patients (15-58 years old) were enrolled; all received treatment. At primary analysis, both co-primary efficacy endpoints were met. Estimated mean proportion of patients with hemolysis control was 78.7% (95% CI: 67.8-86.6). Difference between proportion of patients with transfusion avoidance from baseline through W25 (51.0%; n = 26) versus within 24 weeks of prescreening (0%) was statistically significant (p < .0001). No adverse events led to treatment discontinuation. One treatment-unrelated death (subdural hematoma following a fall) occurred. In conclusion, crovalimab, with every-4-weeks subcutaneous dosing is efficacious and well tolerated in complement inhibitor-naive patients with PNH.

Effect of visit-to-visit blood pressure variability on mild cognitive impairment and probable dementia in hypertensive patients receiving standard and intensive blood pressure treatment.

Background: High visit-to-visit blood pressure variability (BPV) and hypertension are risk factors for mild cognitive impairment (MCI) and probable dementia (PD). Few articles assessed the effect of BPV on the MCI and PD in intensive blood pressure treatment and the different functions of three types of visit-to-visit BPV: systolic blood pressure variability (SBPV), diastolic blood pressure variability (DBPV) and pulse pressure variability (PPV). Methods: We performed a post hoc analysis of the SPRINT MIND trial. The primary outcomes were MCI and PD. BPV was measured by average real variability (ARV). The Kaplan-Meier curves were used to clarify the difference in tertiles of BPV. We fit Cox proportional hazards models to our outcome. We also did an interaction analysis between the intensive and standard groups. Results: We enrolled 8,346 patients in the SPRINT MIND trial. The incidence of MCI and PD in the intensive group was lower than that in the standard group. 353 patients had MCI and 101 patients had PD in the standard group while 285 patients had MCI and 75 patients had PD in the intensive group. Tertiles with higher SBPV, DBPV and PPV in the standard group had a higher risk of MCI and PD (all p < 0.05). Meanwhile, higher SBPV and PPV in the intensive group were associated with an increased risk of PD (SBPV: HR(95%) = 2.1 (1.1-3.9), p = 0.026; PPV: HR(95%) = 2.0 (1.1-3.8), p = 0.025 in model 3) and higher SBPV in the intensive group was associated with an increased risk of MCI(HR(95%) = 1.4 (1.2-1.8), p < 0.001 in model 3). The difference between intensive and standard blood pressure treatment was not statistically significant when we considered the effect of the higher BPV on the risk of MCI and PD (all p for interaction >0.05). Conclusion: In this post hoc analysis of the SPRINT MIND trial, we found that higher SBPV and PPV were associated with an increased risk of PD in the intensive group, and higher SBPV was associated with an increased risk of MCI in the intensive group. The effect of higher BPV on the risk of MCI and PD was not significantly different in intensive and standard blood pressure treatment. These findings emphasized the need for clinical work to monitor BPV in intensive blood pressure treatment.

The novel HLA-A*02:07:23 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-A*02:07:23 differs from HLA-A*02:07:01:01 by one nucleotide in exon 2.

Pediatric chemotherapy versus allo-HSCT for adolescent and adult Philadelphia chromosome-negative ALL in first complete remission: a meta-analysis.

Pediatric-inspired chemotherapy significantly improves survival for adolescent and adult patients with acute lymphoblastic leukemia (ALL). However, the benefits over allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear. To compare clinical outcomes between pediatric-inspired chemotherapy and allo-HSCT in consolidation therapy of adolescent and adult Philadelphia chromosome-negative (Ph-neg) ALL in first complete remission (CR1), related studies from MEDLINE, Embase, and Cochrane Controlled Register of Trials updated to July 2022 were searched. A total of 13 relevant trials including 3161 patients were included in the meta-analysis. Compared with allo-HSCT, pediatric-inspired chemotherapy achieved better OS (hazard risk (HR), 0.53; 95% confidence interval (CI), 0.41 to 0.68) and DFS (HR, 0.64; 95% CI, 0.48 to 0.86), with a significant reduction in NRM (risk ratio (RR), 0.30; 95% CI, 0.18 to 0.51), but no difference in the relapse rate (RR, 1.13; 95% CI, 0.93 to 1.39). When only studies based on intention-to-treat analysis were included, pediatric-inspired chemotherapy consistently conferred a survival advantage. In subgroup analyses, patients with baseline high-risk features demonstrated similar OS and DFS between pediatric-style chemotherapy and allo-HSCT, while pediatric-style chemotherapy had an OS and DFS advantage in standard-risk subgroup. Particularly, patients with positive minimal residual disease (MRD) achieved better OS and DFS if proceeded to allo-HSCT.

Intertemporal Decision-making and Risk Decision-making Among Habitual Nappers Under Nap Sleep Restriction: A Study from ERP and Time-frequency.

Sleep restriction affects people's decision-making behavior. Nap restriction is a vital subtopic within sleep restriction research. In this study, we used EEG to investigate the impact of nap sleep restriction on intertemporal decision-making (Study 1) and decision-making across risky outcomes (Study 2) from ERP and time-frequency perspectives. Study 1 found that habitual nappers restricting their naps felt more inclined to choose immediate, small rewards over delayed, large rewards in an intertemporal decision-making task. P200s, P300s, and LPP in our nap-restriction group were significantly higher than those in the normal nap group. Time-frequency results showed that the delta band (1 ~ 4 Hz) power of the restricted nap group was significantly higher than that of the normal nap group. In Study 2, the nap-restriction group was more likely to choose risky options. P200s, N2s, and P300s in the nap deprivation group were significantly higher than in the normal nap group. Time-frequency results also found that the beta band (11 ~ 15 Hz) power of the restricted nap group was significantly lower than that of the normal nap group. The habitual nappers became more impulsive after nap restriction and evinced altered perceptions of time. The time cost of the LL (larger-later) option was perceived to be too high when making intertemporal decisions, and their expectation of reward heightened when making risky decisions-believing that they had a higher probability of receiving a reward. This study provided electrophysiological evidence for the dynamic processing of intertemporal decision-making, risky decision-making, and the characteristics of nerve concussions for habitual nappers.

Touchable Gustation via a Hoffmeister Gel Iontronic Sensor.

A particular sense, touchable gustation, was achieved. We proposed a chemical-mechanical interface strategy with an iontronic sensor device. A conductive hydrogel, amino trimethylene phosphonic acid (ATMP) assisted poly(vinyl alcohol) (PVA), was employed as the dielectric layer of the gel iontronic sensor. The Hofmeister effect of the ATMP-PVA hydrogel was well investigated to establish the quantitative description of the gel elasticity modulus to chemical cosolvents. The mechanical properties of hydrogels can be transduced extensively and reversibly by regulating the aggregation state of polymer chains with hydrated ions or cosolvents. Scanning electron microscopy (SEM) images of ATMP-PVA hydrogel microstructures stained with different soaked cosolvents present different networks. The information on different chemical components will be stored in the ATMP-PVA gels. The flexible gel iontronic sensor with a hierarchical pyramid structure performed high linear sensitivity of 3224.2 kPa-1 and wide pressure response in the range of 0-100 kPa. The finite element analysis proved the pressure distribution at the gel interface of the gel iontronic sensor and the capacitation-stress response relation. Various cations, anions, amino acids, and saccharides can be discriminated, classified, and quantified with the gel iontronic sensor. The Hofmeister effect regulated chemical-mechanical interface performs the response and conversion of biological/chemical signals into electrical output in real time. The particular function to tactile with gustation percept will contribute promising applications in the human-machine interaction, humanoid robot, clinic treatment, or athletic training optimization.

Explainable Deep-Learning-Assisted Sweat Assessment via a Programmable Colorimetric Chip.

Multianalytes and individual differences of biofluids (such as blood, urine, or sweat) pose enormous complexity and challenges to rapid, facile, high-throughput, and accurate clinical analysis or health assessment. Deep-learning (DL)-assisted image analysis has been demonstrated to be an efficient big data process which shows accurate individual identification. However, the data-driven "black boxes" of current DL algorithms are suffering from the nontransparent inner working mechanism. In this work, we designed a programmable colorimetric chip with explainable DL to approach accurate classification and quantification analysis of sweat samples. Gel (sodium alginate) capsules with different indicators were adopted to combinate as designed programmable colorimetric chips. We collected 4600 colorimetric response images as the data set and assessed two DL algorithms and seven machine learning (ML) algorithms. Glucose, pH, and lactate in human sweat could be facilely and 100% accurately classified and quantified by the convolutional neural network (CNN) DL algorithm, and the testing results of actual sweat via the DL-assisted colorimetric approach match 91.0-99.7% with the laboratory measurements. Class activation mapping (CAM) was processed to visualize the inner working mechanism of CNN operation, which could help to verify and explicate the design rationality of colorimetric chips. The explainable DL-assisted programmable colorimetric chip provided an "end-to-end" strategy to ascertain the black box of the DL algorithm, promoted software design or principium optimization, and contributed facile indicators for clinical monitoring, disease prevention, and even new scientific discoveries.

A Rainbow Structural Color by Stretchable Photonic Crystal for Saccharide Identification.

Photonic crystals (PCs) with fascinating structural color nanomaterials present effectively spontaneous emission modulation and selectively optical signal amplification. Stretchability or elasticity could enable the feasible tunability for structural colors. Aimed at the regulation of structural colors, we endeavored to achieve the PC nanomatrix evolution and optical property during stretching. In this work, a rainbow structural color by stretchable PCs was exploited to provide abundant optical information for multianalyte recognition. The finite element analysis proved the electric field distribution in the PC matrix, which completely matched with the phenomenon of the measured PC spectra. By simply employing analysis of the multistate PC during stretching, the mono PC matrix chip can differentially enhance fluorescence signals in broad spectral regions, resulting in diverse sensing information for high-efficiency multianalysis. The stretchable PC chip can facilely discriminate 14 similar structured saccharides with a minimum concentration of 10-7 M using only one fluorescence complex. Furthermore, saccharides in different concentrations, mixtures, and real samples (beverages and sweets) also can be successfully distinguished. The exploration on fluorescent stretch dependence behavior of the photonic crystal contributes the biomatching optical platform for wearable devices, dynamic environment, clinical, or health monitoring auxiliary.