Knowledge and attitude toward postoperative antithrombotic management and prevention in patients with coronary revascularization: a cross-sectional study.

Background: This study aimed to explore the knowledge and attitude (KA) toward postoperative antithrombotic management and prevention among coronary artery disease (CAD) patients who underwent coronary revascularization. Methods: This cross-sectional study enrolled CAD outpatients and inpatients between May and December 2023 at Kailuan Medical Group at Tangshan. Basic demographic characteristics and KA scores were collected through a self-made questionnaire. Results: This study included 523 valid questionnaires. The mean knowledge and attitude scores were 13.20 ± 6.20 (range: 0-26) and 43.68 ± 6.01 (range: 21-50), respectively, indicating poor knowledge and favorable attitude. Multivariable logistic regression analysis showed that junior high school education (OR = 2.160, P = 0.035), high school or technical school education (OR = 2.356, P = 0.039), and monthly average income >5,000 RMB (OR = 3.407, P = 0.002) were independently associated with knowledge. Knowledge (OR = 1.095, P = 0.002), BMI ≥ 24.0 kg/m2 (OR = 0.372, P = 0.011), junior high school (OR = 3.699, P = 0.002), high school or technical school (OR = 2.903, P = 0.028), high associate degree or above education (OR = 6.068, P = 0.014), monthly average income 3,000-5,000 RMB (OR = 0.296, P = 0.005), monthly average income > 5,000 RMB (OR = 0.225, P = 0.021), with hypertension (OR = 0.333, P = 0.003), blood tests every 2-3 weeks (OR = 10.811, P = 0.011), blood tests every month (OR = 4.221, P = 0.024), and blood tests every 2-3 months (OR = 3.342, P = 0.033) were independently associated with attitude. Conclusion: CAD patients who underwent coronary revascularization had poor knowledge but favorable attitudes toward postoperative antithrombotic management and prevention. The study underscores the need for targeted education, especially for individuals with lower education and income levels, ultimately improving patient compliance and cardiovascular outcomes.

Sequential high-recovery nanofiltration and electrochemical degradation for the treatment of pharmaceutical wastewater.

The presence of antibiotics in aquatic ecosystems poses a significant concern for public health and aquatic life, owing to their contribution to the proliferation of antibiotic-resistant bacteria. Effective wastewater treatment strategies are needed to ensure that discharges from pharmaceutical manufacturing facilities are adequately controlled. Here we propose the sequential use of nanofiltration (NF) for concentrating a real pharmaceutical effluent derived from azithromycin production, followed by electrochemical oxidation for thorough removal of pharmaceutical compounds. The NF membrane demonstrated its capability to concentrate wastewater at a high recovery value of 95 % and 99.7 ± 0.2 % rejection to azithromycin. The subsequent electrochemical oxidation process completely degraded azithromycin in the concentrate within 30 min and reduced total organic carbon by 95 % in 180 min. Such integrated treatment approach minimized the electrochemically-treated volume through a low-energy membrane approach and enhanced mass transfer towards the electrodes, therefore driving the process toward zero-liquid-discharge objectives. Overall, our integrated approach holds promises for cost-effective and sustainable removal of trace pharmaceutical compounds and other organics in pharmaceutical wastewater.

Direct Regeneration of Spent Lithium-Ion Battery Cathodes: From Theoretical Study to Production Practice.

Direct regeneration method has been widely concerned by researchers in the field of battery recycling because of its advantages of in situ regeneration, short process and less pollutant emission. In this review, we firstly analyze the primary causes for the failure of three representative battery cathodes (lithium iron phosphate, layered lithium transition metal oxide and lithium cobalt oxide), targeting at illustrating their underlying regeneration mechanism and applicability. Efficient stripping of material from the collector to obtain pure cathode material has become a first challenge in recycling, for which we report several pretreatment methods currently available for subsequent regeneration processes. We review and discuss emphatically the research progress of five direct regeneration methods, including solid-state sintering, hydrothermal, eutectic molten salt, electrochemical and chemical lithiation methods. Finally, the application of direct regeneration technology in production practice is introduced, the problems exposed at the early stage of the industrialization of direct regeneration technology are revealed, and the prospect of future large-scale commercial production is proposed. It is hoped that this review will give readers a comprehensive and basic understanding of direct regeneration methods for used lithium-ion batteries and promote the industrial application of direct regeneration technology.

Synergistic effect on simultaneous treatment of Cr(VI) and chloramphenicol using a non-thermal plasma technology.

Toxic organic and heavy metal contaminants commonly exist in industrial waste stream(s) and treatment is of great challenge. In this study, a dielectric barrier discharge (DBD) non-thermal plasma technology was employed for the simultaneous treatment of two important contaminants, chloramphenicol (CAP) and Cr(VI) in an aqueous solution through redox transformations. More than 70% of CAP and 20% of TOC were degraded in 60 min, while Cr(VI) was completely removed in 10 min. The hydroxyl radicals were the main active species for the degradation. Meanwhile, the consumption of hydroxyl radicals was beneficial to the reduction of Cr(VI). The synergistic effect was investigated between CAP degradation and Cr(VI) reduction. The reduction of Cr(VI) would be enhanced in the presence of CAP with a low concentration and could be inhibited under a high concentration, because part of hydroxyl radicals could be consumed by the low-concentration CAP and the obtained intermediates with a higher kinetic rate. However, CAP with a high concentration could react with such reductive species as eaq- and •H, which could compete with Cr(VI) and inhibit the reduction. In addition, the presence of Cr(VI) enhanced the degradation and mineralization of CAP; the study of obtained intermediates indicated that the presence of Cr(VI) changed the degradation path of CAP as Cr(VI) would react with reductive species, enhance the generation of hydroxyl radicals, and cause more hydroxylation reactions. Moreover, the mechanism for the simultaneous redox transformations of CAP and Cr(VI) was illustrated. This study indicates that the DBD non-thermal plasma technology can be one of better solutions for simultaneous elimination of heavy metal and organic contaminants in aquatic environments.

Processing of angiocrine alarmin IL-1α in endothelial cells promotes lung and liver fibrosis.

BACKGROUND: Fibrosis results from excessive scar formation after tissue injury. Injured cells release alarmins such as interleukin 1 (IL-1) α and ß as primary mediators initiating tissue repair. However, how alarmins from different cell types differentially regulate fibrosis remains to be explored. METHODS: Here, we used tissue specific knockout strategy to illustrate a unique contribution of endothelial cell-derived IL-1α to lung and liver fibrosis. The two fibrotic animal model triggered by bleomycin and CCl4 were used to study the effects of endothelial paracrine/angiocrine IL-1α in fibrotic progression. Human umbilical vein endothelial cells (HUVEC) were performed to explore the production of angiocrine IL-1α at both transcriptional and post-transcriptional levels in vitro. RESULTS: We found that endothelial paracrine/angiocrine IL-1α primarily promotes lung and liver fibrosis during the early phase of organ repair. By contrast, myeloid cell-specific ablation of IL-1α in mice resulted in little influence on fibrosis, suggesting the specific pro-fibrotic role of IL-1α from endothelial cell but not macrophage. In vitro study revealed a coordinated regulation of IL-1α production in human primary endothelial cells at both transcriptional and post-transcriptional levels. Specifically, the transcription of IL-1α is regulated by RIPK1, and after caspase-8 (CASP8) cleaves the precursor form of IL-1α, its secretion is triggered by ion channel Pannexin 1 upon CASP8 cleavage. CONCLUSIONS: Endothelial cell-produced IL-1α plays a unique role in promoting organ fibrosis. Furthermore, the release of this angiocrine alarmin relies on a unique molecular mechanism involving RIPK1, CASP8, and ion channel Pannexin 1.

A close-up of regulatory networks and signaling pathways of MKK5 in biotic and abiotic stresses.

Mitogen-activated protein Kinase Kinase 5 (MKK5) is a central hub in the complex phosphorylation chain reaction of the Mitogen-activated protein kinases (MAPK) cascade, regulating plant responses to biotic and abiotic stresses. This review manuscript aims to provide a comprehensive analysis of the regulatory mechanism of the MKK5 involved in stress adaptation. This review will delve into the intricate post-transcriptional and post-translational modifications of the MKK5, discussing how they affect its expression, activity, and subcellular localization in response to stress signals. We also discuss the integration of the MKK5 into complex signaling pathways, orchestrating plant immunity against pathogens and its modulating role in regulating abiotic stresses, such as: drought, cold, heat, and salinity, through the phytohormonal signaling pathways. Furthermore, we highlight potential applications of the MKK5 for engineering stress-resilient crops and provide future perspectives that may pave the way for future studies. This review manuscript aims to provide valuable insights into the mechanisms underlying MKK5 regulation, bridge the gap from numerous previous findings, and offer a firm base in the knowledge of MKK5, its regulating roles, and its involvement in environmental stress regulation.

Solid-Emission-Tunable Squaraine with Thermal-Promoted Aggregate-State Transitions for Fast Thermal History Sensing.

Determining thermal history is crucial in many industrial processes, but reliable and sensitive organic thermal history indicators are currently absent. Herein, we report on the development of a squaraine-based fluorescent molecule, DPEA-SQ, for the detection of thermal exposure histories up to 436 K. DPEA-SQ forms multiple single crystals (DPEA-SQ-I, DPEA-SQ-II, and DPEA-SQ-III) with different conformations and aggregate-state packing modes, contributing to their different fluorescence wavelengths, lifetimes, and efficiencies. Interestingly, DPEA-SQ-I and DPEA-SQ-III undergo aggregate-state structural transitions to form the thermodynamically more stable DPEA-SQ-II, which are accompanied by changes in their fluorescence. By taking advantage of similar aggregate-state structural transformations during heating, a high-temperature thermal exposure history of up to 436 K is recorded and reflected by their fluorescence. To demonstrate the potential practical applications of DPEA-SQ, a DPEA-SQ-Powder/PDMS film is prepared and coated on an electric circuit board, which enables real-time monitoring of localized overheating by the naked eye. Additionally, the fluorescence peaks of DPEA-SQ-Powder and DPEA-SQ-Powder/PDMS films remain unchanged after storage at 373 K for 52 days, demonstrating high aggregate-state stability. The fast and reliable responses of this system make it an excellent candidate for the detection of overtemperature traces in electronic components and circuit diagnosis.

Newly graphene/polypyrrole (rGO/PPy) modified carbon felt as bio-cathode in bio-electrochemical systems (BESs) achieving complete denitrification.

Nitrate reduction in bio-electrochemical systems (BESs) has attracted wide attention due to its low sludge yields and cost-efficiency advantages. However, the high resistance of traditional electrodes is considered to limit the denitrification performance of BESs. Herein, a new graphene/polypyrrole (rGO/PPy) modified electrode is fabricated via one-step electrodeposition and used as cathode in BES for improving nitrate removal from wastewater. The formation and morphological results support the successful formation of rGO/PPy nanohybrids and confirm the part covalent bonding of Py into GO honeycomb lattices to form a three-dimensional cross-linked spatial structure. The electrochemical tests indicate that the rGO/PPy electrode outperforms the unmodified electrode due to the 3.9-fold increase in electrochemical active surface area and 6.9-fold decrease in the charge transfer resistance (Rct). Batch denitrification activity tests demonstrate that the BES equipped with modified rGO/PPy biocathode could not only achieve the full denitrification efficiency of 100% with energy recovery (15.9 × 10-2 ± 0.14 A/m2), but also favor microbial attach and growth with improved biocompatible surface. This work provides a feasible electrochemical route to fabricate and design a high-performance bioelectrode to enhance denitrification in BESs.

Whole-body water mass and kidney function: a Mendelian randomization study.

Background: The morbidity and mortality of chronic kidney disease (CKD) are increasing worldwide, making it a serious public health problem. Although a potential correlation between body water content and CKD progression has been suggested, the presence of a causal association remains uncertain. This study aimed to determine the causal effect of body water content on kidney function. Methods: Genome-wide association study summary data sourced from UK Biobank were used to evaluate single-nucleotide polymorphisms (SNPs) associated with whole-body water mass (BWM). The summary statistics pertaining to kidney function were extracted from the CKDGen consortium. The primary kidney function outcome measures included estimated glomerular filtration rate (eGFR), albuminuria, CKD stages 3-5, and rapid progression to CKD (CKDi25). Two-sample Mendelian randomization (MR) analysis estimated a potential causal relationship between the BWM and kidney function. The inverse variance weighted MR method was used as the primary analysis, accompanied by several sensitive MR analyses. Results: The increase of BWM exhibited a correlation with a reduction in eGFR (ß = -0.02; P = 6.95 × 10-16). Excluding 13 SNPs responsible for pleiotropy (P = 0.05), the increase of BWM was also associated with the decrease of the ratio of urinary albumin to creatinine (ß = -0.16; P = 5.91 × 10-36). For each standard deviation increase in BWM, the risk of CKD stages 3-5 increases by 32% (OR, 1.32; 95% CI, 1.19-1.47; P = 1.43 × 10-7), and the risk of CKDi25 increases by 22% (OR, 1.22; 95% CI, 1.07-1.38; P = 0.002). Conclusion: The increase of BWM is associated with impaired kidney function. Proactively managing body water content is of great significance in preventing the progression of CKD.

Risk factors of different mortality periods in older patients with end-stage renal disease undergoing urgent-start peritoneal dialysis: a retrospective observational study.

BACKGROUND: The first six months of therapy represents a high-risk period for peritoneal dialysis (PD) failure. The risk of death in the first six months is higher for older patients treated with urgent-start PD (USPD). However, there are still gaps in research on mortality and risk factors for death in this particular group of patients. We aimed to investigate mortality rates and risk factors for death in older patients with end-stage renal disease (ESRD) receiving USPD within and after six months of therapy. METHODS: We retrospectively studied the clinical information of older adults aged ≥ 65 years with ESRD who received USPD between 2013 and 2019 in five Chinese hospitals. Patients were followed up to June 30, 2020. The mortality and risk factors for death in the first six months of USPD treatment and beyond were analyzed. RESULTS: Of the 379 elderly patients in the study, 130 died over the study period. During the follow-up period, the highest number (45, 34.6%) of deaths occurred within the first six months. Cardiovascular disease was the most common cause of death. The baseline New York Heart Association (NYHA) class III-IV cardiac function [hazard ratio (HR) = 2.457, 95% confidence interval (CI): 1.200-5.030, p = 0.014] and higher white blood cell (WBC) count (HR = 1.082, 95% CI: 1.021-1.147, p = 0.008) increased the mortality risk within six months of USPD. The baseline NYHA class III-IV cardiac function (HR = 1.945, 95% CI: 1.149-3.294, p = 0.013), lower WBC count (HR = 0.917, 95% CI: 0.845-0.996, p = 0.040), lower potassium levels (HR = 0.584, 95% CI: 0.429-0.796, p = 0.001), and higher calcium levels (HR = 2.160, 95% CI: 1.025-4.554, p = 0.043) increased the mortality risk after six months of USPD. CONCLUSION: Different risk factors correlated with mortality in older adults with ESRD within and after six months of undergoing USPD, including baseline NYHA class III-IV cardiac function, WBC count, potassium, and calcium levels.

Unraveling the CLCC1 interactome: Impact of the Asp25Glu variant and its interaction with SigmaR1 at the Mitochondrial-Associated ER Membrane (MAM).

The endoplasmic reticulum (ER) plays an indispensable role in cellular processes, including maintenance of calcium homeostasis, and protein folding, synthesized and processing. Disruptions in these processes leading to ER stress and the accumulation of misfolded proteins can instigate the unfolded protein response (UPR), culminating in either restoration of balanced proteostasis or apoptosis. A key player in this intricate balance is CLCC1, an ER-resident chloride channel, whose essential role extends to retinal development, regulation of ER stress, and UPR. The importance of CLCC1 is further underscored by its interaction with proteins localized to mitochondria-associated endoplasmic reticulum membranes (MAMs), where it participates in UPR induction by MAM proteins. In previous research, we identified a p.(Asp25Glu) pathogenic CLCC1 variant associated with retinitis pigmentosa (RP) (CLCC1 hg38 NC_000001.11; NM_001048210.3, c.75C > A; UniprotKB Q96S66). In attempt to decipher the impact of this variant function, we leveraged liquid chromatography-mass spectrometry (LC-MS) to identify likely CLCC1-interacting proteins. We discovered that the CLCC1 interactome is substantially composed of proteins that localize to ER compartments and that the Asp25Glu variant results in noticeable loss and gain of specific protein interactors. Intriguingly, the analysis suggests that the CLCC1Asp25Glu mutant protein exhibits a propensity for increased interactions with cytoplasmic proteins compared to its wild-type counterpart. To corroborate our LC-MS data, we further scrutinized two novel CLCC1 interactors, Calnexin and SigmaR1, chaperone proteins that localize to the ER and MAMs. Through microscopy, we demonstrate that CLCC1 co-localizes with both proteins, thereby validating our initial findings. Moreover, our results reveal that CLCC1 co-localizes with SigmaR1 not merely at the ER, but also at MAMs. These findings reinforce the notion of CLCC1 interacting with MAM proteins at the ER-mitochondria interface, setting the stage for further exploration into how these interactions impact ER or mitochondria function and lead to retinal degenerative disease when impaired.

Serum globulin in children with myasthenia gravis: predicting relapse and prognosis.

OBJECTIVE: Serum globulin is associated with inflammatory or immune disorders. However, it has not been established whether it is associated with myasthenia gravis (MG). We investigated the association between globulin with relapse and prognosis in children with MG. METHODS: A cohort of 148 MG cases and 150 healthy children were retrospectively enrolled from January 2015 to December 2021. Multivariate logistic and Cox regression models were used to analyze the treatment outcomes and recurrence of case group, exploring the influence of globulin. RESULTS: Compared with the control group, globulin levels in the MG group were slightly increased (t = 7.244, p < 0.001). After a mean follow-up of 2.25 ± 1.05 years, 35 cases relapsed, with a relapse rate of 23.65%. Logistic regression analysis showed that globulin levels at admission [adjusted odds ratio (OR) = 1.233, 95% confidence interval (CI) 1.028-1.472, p = 0.018] were independent risk factors for relapse. Cox regression analysis confirmed that globulin levels at admission affects relapse-free time [adjusted hazard ratio (HR) = 0.552, 95% CI 0.357-0.852, p = 0.007]. Receiver operating characteristic curve determined 25.10 as the optimal cutoff value for globulin. Cox regression showed that high globulin levels (>25.10) at admission (adjusted HR = 0.607, 95% CI 0.383-0.961, p = 0.033) were independent risk factors for poor therapeutic outcomes at follow-up. Ordinal logistic regression showed that globulin affects the treatment plan (OR = 1.445, 95% CI 1.223-1.847, p = 0.014). CONCLUSIONS: Elevated globulin levels in children with MG on admission predicts a high relapse rate and poor long-term therapeutic efficacies.

Serum globulin in children with myasthenia gravis: predicting relapse and prognosisFirst, the globulin in the MG children was higher than in the healthy controls, and there was some correlation between the globulin and the level of systemic inflammation.Second, globulin has been associated with relapse of MG in children. The higher the globulin, the higher the relapse rate and the shorter the time to prevent a relapse.Third, both initial and final globulin were related to the effect of MG in children, and the higher the long-term effect, the worse the long-term effect. It also influenced the change in treatment plan.

Resourceful application and mechanism of oyster shell-microalgae synergistic system：Sustainable treatment of harsh low carbon nitrogen ratio actual wastewater.

Microalgal technology holds great promise for both low C/N wastewater treatment and resource recovery simultaneously. Nevertheless, the advancement of microalgal technology is hindered by its reduced nitrogen removal efficiency in low C/N ratio wastewater. In this work, microalgae and waste oyster shells were combined to achieve a total inorganic nitrogen removal efficiency of 93.85% at a rate of 2.05 mg L-1 h-1 in low C/N wastewater. Notably, over four cycles of oyster shell reuse, the reactor achieved an average 85% ammonia nitrogen removal extent, with a wastewater treatment cost of only $0.092/ton. Moreover, microbial community analysis during the reuse of oyster shells revealed the critical importance of timely replacement in inhibiting the growth of non-functional bacteria (Poterioochromonas_malhamensi). The work demonstrated that the oyster shell - microalgae system provides a time- and cost-saving, environmental approach for the resourceful treatment of harsh low C/N wastewater.

Alleviating Neonatal Intensive Care Unit Stress: A Chinese Medicine Approach in Neonatal Rats.

Background: Premature infants are exposed to numerous stressors in neonatal intensive care unit (NICU) during a crucial period for brain development; this period exerts long-term influences on cognitive and behavioral development. Aims: To evaluate the effect of NICU-related stress on neonatal rat pups and explore the effect of Chinese medicine treatment (CMT). Methods: Sixty male rat pups were randomly assigned to three groups: the control group, the NICU group (NICU-related stress), and the CMT group (NICU-related stress plus CMT). All stressors and interventions were administered from 0 to 7 days after birth. Body weight, serum corticosterone levels, and behavior in the open field (OF) test, elevated plus maze (EPM) test, sucrose preference test, and Morris water maze (MWM) test were recorded, and blood samples were collected at five different time points (T0, T1, T2, T3, and T4). Results: The body weights of rats in the CMT and control groups were heavier than those in the NICU group in both early life and adulthood (P < 0.05). Serum corticosterone levels significantly differed with time (except T0 vs. T1 and T3 vs. T4) but did not significantly differ among the three groups (F = 0.441, P = 0.894). Regardless of age, spatial memory and anxiety-like and depression-like behavior did not differ among the three groups. Conclusion: NICU-related stress exerted a long-term effect on rat growth and development but did not affect spatial memory, anxiety-like behavior, depression-like behavior, or serum corticosterone levels. CMT alleviated the impact of NICU-related stress on rats and promoted the growth and development of neonatal rats.

Unraveling the Activity and Mechanism of TM@g-C4N3 Electrocatalysts in the Oxygen Reduction Reaction.

In this work, a high-throughput screening strategy and density functional theory (DFT) are jointly employed to identify high-performance TM@g-C4N3 (TM = 3d, 4d, 5d transition metals) single-atom catalysts (SACs) for the oxygen reduction reaction (ORR). Comprehensive studies demonstrated that Cu@, Zn@, and Ag@g-C4N3 show high ORR catalytic activities under both acidic and alkaline conditions with favorable overpotentials (ηORR) of 0.70, 0.89, and 0.89 V, respectively; among them, Cu@g-C4N3 is the best candidate. The ORR follows a four-electron mechanism with the final product H2O/OH-. Cu@, Zn@, and Ag@g-C4N3 catalysts also exhibit good thermal (500 K) and electrochemical (0.93-3.14 V) stabilities. Cu@, Zn@, and Ag@g-C4N3 demonstrate superior activities with low ηORR due to its moderate adsorption strength of *OH. The ηORR and the Gibbs free energy changes of *OH (ΔG4(acidic)/ΔG4(alkaline)) resemble a volcano-type relationship under acidic/alkaline conditions, respectively. Additionally, the O-O bond length in *OOH emerged as an effective structural descriptor for rapidly identifying the promising electrocatalysts. This research provides valuable insights into the origin of the ORR activity on TM@g-C4N3 and offers useful guidance for the efficient exploration of high-performance catalyst candidates.

Bidirectional Enhancement of Nitrogen Removal by Indigenous Synergetic Microalgal-Bacterial Consortia in Harsh Low-C/N Wastewater.

Conventional microalgal-bacterial consortia have limited capacity to treat low-C/N wastewater due to carbon limitation and single nitrogen (N) removal mode. In this work, indigenous synergetic microalgal-bacterial consortia with high N removal performance and bidirectional interaction were successful in treating rare earth tailing wastewaters with low-C/N. Ammonia removal reached 0.89 mg N L-1 h-1, 1.84-fold more efficient than a common microalgal-bacterial system. Metagenomics-based metabolic reconstruction revealed bidirectional microalgal-bacterial interactions. The presence of microalgae increased the abundance of bacterial N-related genes by 1.5- to 57-fold. Similarly, the presence of bacteria increased the abundance of microalgal N assimilation by 2.5- to 15.8-fold. Furthermore, nine bacterial species were isolated, and the bidirectional promotion of N removal by the microalgal-bacterial system was verified. The mechanism of microalgal N assimilation enhanced by indole-3-acetic acid was revealed. In addition, the bidirectional mode of the system ensured the scavenging of toxic byproducts from nitrate metabolism to maintain the stability of the system. Collectively, the bidirectional enhancement system of synergetic microalgae-bacteria was established as an effective N removal strategy to broaden the stable application of this system for the effective treatment of low C/N ratio wastewater.

Video-electroencephalographic findings and clinical characteristics of bathing seizures in children.

Objective: To explore the electroencephalogram (EEG) and clinical characteristics of childhood bathing epilepsy. Methods: We conducted a prospective summary of the clinical data from 10 children with bathing epilepsy who were admitted to Hunan Children's Hospital from April 2019 to November 2023 and analyzed their EEGs and clinical characteristics. Results: Our 10 patients included eight males and two females, with seizure-onset ages ranging from 4 months and 20 days to 14 months. Nine cases showed normal intellectual development, and one case manifested delayed development. The Video-EEG (VEEG) findings showed that nine cases exhibited normal background with no interictal epileptic discharge. The seizures were characterized by lip cyanosis, tachycardia or bradycardia, weakness, paleness, and loss of consciousness. Ictal EEG revealed rhythmic fast waves, spike waves, spike-slow waves, or slow and sharp-wave activity over the temporal region (eight cases) or the occipital and temporal regions (one case), finally evolving into a delta rhythm that lasted for 57-201 s. These children exhibited no seizures after discontinuing bathing and were not administered antiseizure medication. The interictal EEG of one case reflected mild slow background and focal interictal epileptic discharge; and her semiology was eyes gazing to right, with clonic movements of the right face and lips, lip cyanosis, bradycardia, and impaired consciousness. Ictal EEG showed spike-wave and spike-slow-wave rhythms over the left central, parietal, and temporal regions; these then spread to the left hemisphere, lasting for approximately 104 s. This patient did not exhibit bathing seizures after stopping her bathing but later experienced frequent spontaneous and drug-resistant seizures. The interictal EEG background slowed down, while focal epileptic discharge increased. Her intellectual development was significantly delayed, and a novel pathogenic mutation in the SMC1A gene, c.298+2T>C, was detected. She was diagnosed with developmental and epileptic encephalopathy. Conclusion: A majority of children with bathing epilepsy in our study showed focal autonomic seizures accompanied by impaired consciousness. Stopping bathing could control the seizures and showed a good prognosis. A few infants manifested a poor prognosis, and we posit that bathing seizure rarely constitute the early manifestations of developmental and epileptic encephalopathy. VEEG findings and clinical features can also indicate the prognosis.

CD19-CAR-DNT cells (RJMty19) in patients with relapsed or refractory large B-cell lymphoma: a phase 1, first-in-human study.

Background: Current approved chimeric antigen receptor (CAR) T-cell products are autologous cell therapies that are costly and poorly accessible to patients. We aimed to evaluate the safety and antitumor activity of a novel off-the-shelf anti-CD19 CAR-engineered allogeneic double-negative T cells (RJMty19) in patients with relapsed/refractory large B-cell lymphoma. We report the results from a first-in-human, open-label, single-dose, phase 1 study of allogeneic CD19-specific CAR double-negative T (CAR-DNT) cells. Methods: Eligibility criteria included the presence of measurable lesions, at least 2 lines of prior immunochemotherapy, and an ECOG score of 0-1. We evaluated four dose levels (DL) of RJMty19 in a 3 + 3 dose-escalation scheme: 1 × 106, 3 × 106, 9 × 106 and 2 × 107 CAR-DNT cells per kilogram of body weight. All patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide. The primary endpoints were dose-limiting toxicities (DLTs), incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of standard cellular pharmacokinetic parameters, immunogenicity, objective response rates (ORR), and disease control rate (DCR) per Lugano 2014 criteria. Findings: A total of 12 patients were enrolled between 22 July 2022 and 27 July 2023. Among these patients, 66% were classified as stage IV, 75% had an IPI score of 3 or higher, representing an intermediate risk or worse. The maximum tolerated dose was not reached because no DLT was observed. Four patient experienced grade 1 or 2 cytokine release syndrome and dizziness. The most common AEs were hematologic toxicities, including neutropenia (N = 12, 100%), leukopenia (N = 12, 100%), lymphopenia (N = 10, 83%), thrombocytopenia (N = 6, 50%), febrile neutropenia (N = 3, 25%), and anemia (N = 3, 25%). Seven subjects died till the cut-off date, five of them died of disease progression and two of them died of COVID 19. In all patients (N = 12), the ORR was 25% and CRR was 8.3%. DL1 and DL2 patients benefited less from the therapy (ORR: 17%, N = 1; DCR: 33%, N = 2). However, all DL3 patients achieved disease control (N = 3, 100%), and all DL4 patients achieved objective response (N = 3, 100%). Interpretation: Our results demonstrate that CD19-CAR-DNT cells appear to be well tolerated with promising antitumor activity in LBCL patients. Further study of this product with a larger sample size is warranted. This phase 1 study is registered on clinicaltrials.gov (NCT05453669). Funding: Wyze Biotech. Co., Ltd.

CRISPR/Cas genome editing in plants: mechanisms, applications, and overcoming bottlenecks.

The CRISPR/Cas systems have emerged as transformative tools for precisely manipulating plant genomes and enhancement. It has provided unparalleled applications from modifying the plant genomes to resistant enhancement. This review manuscript summarises the mechanism, application, and current challenges in the CRISPR/Cas genome editing technology. It addresses the molecular mechanisms of different Cas genes, elucidating their applications in various plants through crop improvement, disease resistance, and trait improvement. The advent of the CRISPR/Cas systems has enabled researchers to precisely modify plant genomes through gene knockouts, knock-ins, and gene expression modulation. Despite these successes, the CRISPR/Cas technology faces challenges, including off-target effects, Cas toxicity, and efficiency. In this manuscript, we also discuss these challenges and outline ongoing strategies employed to overcome these challenges, including the development of novel CRISPR/Cas variants with improved specificity and specific delivery methods for different plant species. The manuscript will conclude by addressing the future perspectives of the CRISPR/Cas technology in plants. Although this review manuscript is not conclusive, it aims to provide immense insights into the current state and future potential of CRISPR/Cas in sustainable and secure plant production.

Metal-Free Catalytic Formation of a Donor-Acceptor-Donor Molecule and Its Lewis Acid-Adduct Singlet Diradical with High-Efficient NIR-II Photothermal Conversion.

We have synthesized a quinone-incorporated bistriarylamine donor-acceptor-donor (D-A-D) semiconductor 1 by B(C6F5)3 (BCF) catalyzed C-H/C-H cross coupling via radical ion pair intermediates. Coordination of Lewis acids BCF and Al(ORF)3 (RF=C(CF3)3) to the semiconductor 1 afforded diradical zwitterions 2 and 3 by integer electron transfer. Upon binding to Lewis acids, the LUMO energy of 1 is significantly lowered and the band gap of the semiconductor is significantly narrowed from 1.93 eV (1) to 1.01 eV (2) and 1.06 eV (3). 2 and 3 are rare near-infrared (NIR) diradical dyes with broad absorption both centered around 1500 nm. By introducing a photo BCF generator, 2 can be generated by light-dependent control. Furthermore, the integer electron transfer process can also be reversibly regulated via the addition of CH3CN. In addition, the temperature of 2 sharply increased and reached as high as 110 °C in 10 s upon the irradiation of near-infrared-II (NIR-II) laser (1064 nm, 0.7 W cm-2), exhibiting a fast response to laser. It displays excellent photothermal stability with a photothermal (PT) conversion efficiency of 62.26 % and high-quality PT imaging.