Effects of cations on biofilms in gravity-driven membrane system: Filtration performance and mechanism investigation.

The gravity-driven membrane (GDM) system is desirable for energy-efficient water treatment. However, little is known about the influence of cations on biofilm properties and GDM performance. In this study, typical cations (Ca2+ and Na+) were used to reveal the combined fouling behavior and mechanisms. Results showed that Ca2+ improved the stable flux and pollutant removal efficiency, while Na+ adversely affected the flux. Compared with GDM control, the concentration of pollutants was lower in Ca-GDM, as indicated by the low biomass, proteins, and polysaccharides. A heterogeneous and loose biofilm was observed in the Ca-GDM system, with roughness and porosity increasing by 43.06 % and 32.60 %, respectively. However, Na+ induced a homogeneous and dense biofilm, with porosity and roughness respectively reduced by 17.48 % and 22.04 %. The richness of bacterial communities increased in Ca-GDM systems, while it decreased in Na-GDM systems. High adenosine triphosphate (ATP) concentration in Ca-GDM system was consistent with the abundant bacteria and their high biological activity, which was helpful for the efficient removal of pollutants. The abundance of Apicomplexa, Platyhelminthes, Annelida and Nematoda increased after adding Ca2+, which was related to the formation of loose biofilms. Computational simulations indicated that the free volumes of the biofilms in Ca-GDM and Na-GDM were 13.7 and 13.2 nm3, respectively. The addition of cations changed intermolecular forces, Ca2+ induced bridging effects led to large and loose floc particles, while the significant dehydration of hydrated molecules in the Na-GDM caused obvious aggregation. Overall, microbiological characteristics and contaminant molecular interactions were the main reasons for differences in GDM systems.

Fabrication of Dual-Functional Bacterial-Cellulose-Based Composite Anion Exchange Membranes with High Dimensional Stability and Ionic Conductivity.

Anion exchange membranes (AEMs) are increasingly becoming a popular research area due to their ability to function with nonprecious metals in electrochemical devices. Nevertheless, there is a challenge to simultaneously optimize the dimensional stability and ionic conductivity of AEMs due to the "trade-off" effect. Herein, we adopted a novel strategy of combining filling and cross-linking using functionalized bacterial cellulose (PBC) as a dual-functional porous support and brominated poly(phenylene oxide) (Br-PPO) as the cross-linking agent and filler. The PBC nanofiber framework together with cross-linking can provide a reliable mechanical support for the subsequent filled polymer, thus improving the mechanical properties and effectively limiting the size change of the final quaternized-PPO (QPPO)-filled PBC composite membrane. The composite membrane showed a very low swelling ratio of only 10.35%, even at a high water uptake (81.83% at 20 °C). Moreover, the existence of multiple -NR3+ groups in the cross-link bonds between BC and Br-PPO can provide extra OH- ion transport sites, contributing to the increase in ionic conductivity. The final membrane demonstrated a hydroxide ion conductivity of 62.58 mS cm-1, which was remarkably higher than that of the pure QPPO membrane by up to 235.93% (80 °C). The successful preparation of the PBC3/QPPO membrane provides an effective avenue to tackle the trade-off effect through a dual-functional strategy.

Osteocalcin of maternal and embryonic origins synergize to establish homeostasis in offspring.

Many physiological osteocalcin-regulated functions are affected in adult offspring of mothers experiencing unhealthy pregnancy. Furthermore, osteocalcin signaling during gestation influences cognition and adrenal steroidogenesis in adult mice. Together these observations suggest that osteocalcin may broadly function during pregnancy to determine organismal homeostasis in adult mammals. To test this hypothesis, we analyzed in unchallenged wildtype and Osteocalcin-deficient, newborn and adult mice of various genotypes and origin maintained on different genetic backgrounds, the functions of osteocalcin in the pancreas, liver and testes and their molecular underpinnings. This analysis revealed that providing mothers are Osteocalcin-deficient, Osteocalcin haploinsufficiency in embryos hampers insulin secretion, liver gluconeogenesis, glucose homeostasis, testes steroidogenesis in adult offspring; inhibits cell proliferation in developing pancreatic islets and testes; and disrupts distinct programs of gene expression in these organs and in the brain. This study indicates that osteocalcin exerts dominant functions in most organs it influences. Furthermore, through their synergistic regulation of multiple physiological functions, osteocalcin of maternal and embryonic origins contributes to the establishment and maintenance of organismal homeostasis in newborn and adult offspring.

Composite proton exchange membrane for fuel cells based on chitosan modified by acid-base amphoteric nanoparticles.

Currently, achieving a simultaneous improvement in proton conductivity and mechanical properties is a key challenge in using chitosan (CS) as a proton exchange membrane (PEM) substrate in direct methanol fuel cells (DMFCs). Herein, a novel nanofiller-zwitterionic molecule, (3-(3-aminopropyl) dimethylammonio) propane-1-sulfonate, ADPS)-modified polydopamine (PDA) (PDA-ADPS) was synthesized by the Michael addition reaction and was incorporated into a CS matrix to prepare CS/PDA-ADPS composite membranes. PDA-ADPS, which contains an acid-based ion pair can create new proton conduction channels in the composite membrane, improving proton conductivity. The proton conductivity of the CS/PDA-ADPS composite membrane was as high as 38.4 mS cm-1 at 80 °C. Moreover, due to the excellent compatibility and dispersibility of PDA-ADPS in the CS matrix, the obtained CS/PDA-ADPS composite membranes exhibited favorable mechanical properties. Such outstanding proton conductivity and mechanical properties guarantee good performance of the composite membranes in fuel cells. The peak power density of the CS/PDA-ADPS composite membranes was 30.2 mW cm-2 at 70 °C. This work provides a new strategy for fabricating high-performance CS based PEMs for DMFCs.

Crashworthy optimization of skeleton-filled FRP tubes based on back propagation neural network.

Lightweight composite tubes have been widely used in vehicle safety systems as energy absorbers. To improve the crashworthiness of tubes, composite skeletons with a variety of cross-sectional profiles were ingeniously designed as internal reinforcements. Herein, a novel composite skeleton comprising cross-ribs and an inner circle (OS-skeleton) was proposed and integrally fabricated through the special assembling molds. The novel OS-skeleton presented a steady progressive failure mode under dynamic impact loads, leading to remarkable material utilization and energy absorption characteristics. Subsequently, finite element analysis (FEA) models were developed. The predicted response curves and deformation modes were consistent with the experimental results. Finally, a multi-objective optimization utilizing the back propagation neural network (BPNN) was then conducted to further enhance the mean crushing force (MCF) and specific energy absorption (SEA) by adjusting several structural parameters. The results showed that MCF and SEA increased with the increasing thickness of the skeletons and the number of circumferential ribs. By comparison, the diameter of inner tube and the number of circumferential ribs showed a non-linear relationship with the energy absorption characteristics due to their combined effects. In sum, the proposed composite tubes filled with OS-skeletons could maximize certain aspects of crashworthiness performance through proper structural design, demonstrating great potential for lightweight energy absorbers.

The preparation and characterization of self-healing hydrogels based on polypeptides with a dual response to light and hydrogen peroxide.

Injectable self-healing hydrogels are being widely used in drug delivery, tissue engineering, and other fields. Because of their excellent biocompatibility and biodegradability, polypeptides are an ideal candidate for preparing injectable self-healing hydrogels. In this study, a polypeptide-based hydrogel with dual response to hydrogen peroxide and light was obtained by copolymerizing 4-arm PEG-amine, N-(p-nitrophenoxycarbonyl)-l-methionine, and N-(p-nitrophenoxycarbonyl)-γ-o-nitrobenzyl-l-glutamate. The hydrogel exhibits injectable self-healing behavior due to the hydrophobic interactions among peptide blocks, which also act as the reservoir of hydrophobic drug molecules. In the presence of hydrogen peroxide or under light irradiation, the thioether bond in methionine was oxidized to sulfoxide, whereas the o-nitro benzyl ester bond was broken to form glutamic acid. As a result, the corresponding hydrophobic blocks of polypeptide become hydrophilic, accelerating the release of drug molecules loaded in the polypeptide hydrophobic blocks. Using this technique, the controlled release of hydrophobic drug molecules was achieved. Our efforts could provide a new strategy for the preparation of self-healing hydrogels based on polypeptides with a dual response to hydrogen peroxide and light. In this view, the practical application of polypeptides in drug delivery, tissue engineering, and other fields, could be expanded and advanced.

Evaluation of Front-Face Fluorescence for Assessing Cyanobacteria Fouling in Ultrafiltration.

Cyanobacteria fouling in ultrafiltration (UF) drinking water treatment poses a significant threat to the stability and sustainability of the process. Both phycocyanin found in cyanobacteria and the polymer membrane exhibit strong fluorescence, which could be readily detected using front-face excitation-emission matrix (FF-EEM) spectroscopy. In this study, FF-EEM was employed for the nondestructive and in situ characterization of algae fouling evolution in UF, while also analyzing fouling mechanisms and reversibility. The results indicated that phycocyanin fluorescence on the membrane surface showed a linear correlation with the specific algal cell count on the membrane surface before reaching saturation. As fouling progressed, membrane fluorescence decreased, which was associated with the extent of the surface coverage on the membrane. The plateau in membrane fluorescence indicated full coverage, coinciding with the cake filtration mechanism, cake compression, and deterioration of fouling reversibility. These findings highlight the promise of FF-EEM as a valuable tool for monitoring and evaluating fouling of cyanobacteria in UF systems.

A safe and effective treatment combination of neoadjuvant therapy and surgical resection for metastatic TFE3-rearranged renal cell carcinoma:a case report.

TFE3-rearranged renal cell carcinoma (RCC) is a rare subtype of renal tumor that primarily affects young women and is characterized by early metastasis and a poor prognosis. This case study presents a 29-year-old woman diagnosed with TFE3-rearranged RCC, who initially presented with painless gross hematuria. Computed Tomography (CT) imaging revealed the presence of a solid mass in the left kidney along with retroperitoneal metastasis. The patient received axitinib, a vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI), as first-line neoadjuvant therapy. Subsequent testing confirmed positive expression of programmed death-1 protein L1 (PDL1), leading to the addition of tislelizumab, a PD1 inhibitor, to the treatment regimen. After 8 months, the patient's tumor size and metastases exhibited significant reduction, providing a favorable opportunity for subsequent surgical intervention. The tumor was classified as IV (pT3aN0M1) based on the pathologic stage of the American Joint Committee on Cancer (AJCC, 8th edition, 2017). The patient achieved long-term survival through combined systemic therapy involving surgery and neoadjuvant treatment. At the 30-month follow-up, there was no evidence of tumor recurrence or metastasis.

Dual reinforced composite membranes from in-situ ionic crosslinked quaternized chitosan filled quaternized polyvinylidene fluoride nanofiber for alkaline direct methanol fuel cell.

The main obstacle of high-performance cationic functionalization chitosan (CS) as anion exchange membranes (AEMs) is the trade-off between mechanical stability and ionic conductivity. Here, in-situ ionic crosslinking between the deprotonated hydroxyl group and quaternary ammonium group under alkaline conditions was ingeniously applied to improve the mechanical stability of highly quaternized CS (HQCS) with high IEC (>2 mmol g-1). Meanwhile, to further reduce the swelling and enhance the hydroxide conductivity, a mechanically robust hydroxide ion conduction network, quaternized electrospun poly(vinylidene fluoride) (QPVDF) nanofiber, was subsequently used as the filling substrate of in-situ crosslinked HQCS to prepare dual reinforced thin AEMs. The introduction of a robust QPVDF nanofiber mat can not only greatly improve the mechanical properties and limit swelling, but also create facile ion transport channels. Notably, the HQCS/QPVDF-74.0 composite membrane demonstrates perfect dimensional stability, high mechanical performance and excellent alkaline stability, as well as superior ionic conductivity of 66.2 mS cm-1 at 80 °C. The thus assembled alkaline direct methanol fuel cell displays a maximum power density of 132.30 mW cm-2 using 5 M KOH and 3 M methanol as fuels at 80 °C with satisfactory durability.

Effects of propofol combined with sufentanil on painless gastroscopy and hemodynamics in children under general anesthesia.

OBJECTIVE: To determine the effects of propofol combined with sufentanil on painless gastroscopy and hemodynamics in children under general anesthesia. METHODS: The data of 98 children who received painless gastroscopy in the Children's Hospital of Nanjing Medical University from May 2022 and November 2022 were analyzed retrospectively. Patients anesthetized with propofol (1.5-2 mg/kg) combined with sufentanil (0.03-0.05 µg/kg) were assigned to a study group (n=52), and patients anesthetized with propofol (1.5-2 mg/kg) combined with fentanyl (0.3-0.5 µg/kg) were included in a control group (n=46). The changes in hemodynamic levels (mean arterial pressure (MAP), heart rate (HR) and pulse oxygen saturation (SpO2) at T0 (before anesthesia), T1 (1 min after anesthesia induction), T2 (start of examination), T3 (2 min after the start of examination), and T4 (end of examination) in the two groups were analyzed and compared. The Ramsay sedation score was adopted to evaluate the sedation of the two groups at the anesthesia recovery and at 1 h and 2 h after the anesthesia recovery. The anesthetic effects (time to loss of consciousness, eye opening, and recovery of orientations) of the two groups were analyzed and compared. The excellent and good anesthesia outcomes, hospitalization time and dosage of propofol were compared between the two groups, and the adverse reactions in the two groups during and after the examination were analyzed. RESULTS: At T0, the two groups were not significantly different in the levels of MAP, HR and SpO2 (P>0.05), but at T1, T2, T3, and T4, the study group showed a significantly higher MAP level than the control group (P<0.05). At T1 and T3, the study group exhibited a significantly higher HR level than the control group (P<0.05), and at T2 and T4, the HR level of the two groups was not greatly different (P>0.05). The SpO2 levels at T0, T1, T2, T3, and T4 were not greatly different between the two groups (P>0.05). There was no significant difference in Ramsay score between the two groups at anesthesia recovery and at 1 h and 2 h after the anesthesia recovery (P>0.05). Additionally, the study group experienced significantly earlier time to loss of consciousness, eye opening, and recovery of orientations than the control group (P<0.05). The number of patients with excellent anesthetic outcome in the study group was notably higher than that in the control group (P<0.05). Compared with the control group, the study group consumed less propofol, experienced shorter hospitalization time, and showed a notably lower incidence of adverse reactions (P<0.05). CONCLUSION: For children undergoing painless gastroscopy under general anesthesia, sufentanil combined with propofol can deliver better anesthetic effect than propofol combined with fentanyl, with less effect on hemodynamics and fewer gastroscopy-related adverse reactions.

Osteocalcin of maternal and embryonic origins synergize to establish homeostasis in offspring.

Many physiological functions regulated by osteocalcin are affected in adult offspring of mothers experiencing an unhealthy pregnancy. Furthermore, osteocalcin signaling during gestation influences cognition and adrenal steroidogenesis in adult mice. Together these observations suggest that osteocalcin functions during pregnancy may be a broader determinant of organismal homeostasis in adult mammals than previously thought. To test this hypothesis, we analyzed in unchallenged wildtype and Osteocalcin -deficient, newborn, and adult mice of various genotypes and origin, and that were maintained on different genetic backgrounds, the functions of osteocalcin in the pancreas, liver and testes and their molecular underpinnings. This analysis revealed that providing mothers are themselves Osteocalcin -deficient, Osteocalcin haploinsufficiency in embryos hampers insulin secretion, liver gluconeogenesis, glucose homeostasis, testes steroidogenesis in adult offspring; inhibits cell proliferation in developing pancreatic islets and testes; and disrupts distinct programs of gene expression in these organs and in the brain. This study indicates that through their synergistic regulation of multiple physiological functions, osteocalcin ofmaternal and embryonic origins contributes to the establishment and maintenance of organismal homeostasis in newborn and adult offspring.

Research on the Mechanism of Low-Temperature Oxidation of Asphaltene.

Asphaltene extracted from heavy oil was oxidized by a mixture of propionic anhydride and hydrogen peroxide at a low temperature of 50 °C. Elemental analysis, infrared analysis, proton nuclear magnetic resonance analysis, and gas chromatograph/mass spectrometer analysis results indicated that oxygen addition, side chain cleavage, and condensation reactions mainly occurred in the oxidation process. The oxidation products were divided into 28% methanol solubles and 72% methanol insolubles. There were mainly fatty acids and fatty acid esters in the methanol solubles. There were also small amounts of aromatic compounds with low condensation in the methanol solubles, and the alkyl side chains were mostly short ones. The degree of aromatic ring condensation in the methanol insolubles was slightly higher than that of the pristine asphaltene. There were still some long unbroken chains in the methanol insolubles after the low-temperature reaction. The molecular dynamics simulation results show that the distribution of propionic anhydride around the asphaltene molecules can promote the oxidation of asphaltene. This low-temperature oxidation technology can be used to process asphaltenes to improve the profitability of heavy-oil-processing enterprises.

UV/Fe(II)/S(IV) Pretreatment for Ultrafiltration of Microcystis aeruginosa-Laden Water: Fe(II)/Fe(III) Triggered Synergistic Oxidation and Coagulation.

Ultrafiltration (UF) has been proven effective in removing algae during seasonal algal blooms, but the algal cells and the metabolites can induce severe membrane fouling, which undermines the performance and stability of the UF. Ultraviolet-activated sulfite with iron (UV/Fe(II)/S(IV)) could enable an oxidation-reduction coupling circulation and exert synergistic effects of moderate oxidation and coagulation, which would be highly preferred in fouling control. For the first time, the UV/Fe(II)/S(IV) was systematically investigated as a pretreatment of UF for treating Microcystis aeruginosa-laden water. The results showed that the UV/Fe(II)/S(IV) pretreatment significantly improved the removal of organic matter and alleviated membrane fouling. Specifically, the organic matter removal increased by 32.1% and 66.6% with UV/Fe(II)/S(IV) pretreatment for UF of extracellular organic matter (EOM) solution and algae-laden water, respectively, while the final normalized flux increased by 12.0-29.0%, and reversible fouling was mitigated by 35.3-72.5%. The oxysulfur radicals generated in the UV/S(IV) degraded the organic matter and ruptured the algal cells, and the low-molecular-weight organic matter generated in the oxidation penetrated the UF and deteriorated the effluent. The over-oxidation did not happen in the UV/Fe(II)/S(IV) pretreatment, which may be attributed to the cyclic redox Fe(II)/Fe(III) coagulation triggered by the Fe(II). The UV-activated sulfate radicals in the UV/Fe(II)/S(IV) enabled satisfactory organic removal and fouling control without over-oxidation and effluent deterioration. The UV/Fe(II)/S(IV) promoted the aggregation of algal foulants and postponed the shift of the fouling mechanisms from standard pore blocking to cake filtration. The UV/Fe(II)/S(IV) pretreatment proved effective in enhancing the UF for algae-laden water treatment.

Working and working out: Decision-making inputs connect daily work demands to physical exercise.

Work demands can undermine engagement in physical exercise, posing a threat to employee health and well-being. Integrating resource theories and a novel decision-making theory called the decision triangle, we propose that this effect may emerge because work stress changes the energetic and emotional processes people engage in when making decisions about exercise after work. Using diary-style data across two workweeks (N = 83 workers, 783 days), we used multilevel latent profile analysis to extract common decision input profiles, or daily configurations of energy and affect as key decision-making resources. Consistent with the decision triangle, three profiles emerged: visceral inputs (low energy/high negative affect), automatic inputs (low energy/low negative affect), and logical inputs (high energy/low negative affect). Daily job demands were highest among the visceral profile. In turn, the daily visceral profile related to the lowest likelihood of and intensity of physical exercise after work, especially relative to the daily logical profile. Whether or not those in the daily automatic profile exercised depended on their health orientation, or trait-level value of maintaining personal health. Our results support decision-making as a promising mechanism explaining the link between work demands and healthy leisure choices. Organizational interventions can target work stress, health orientation, or logical decision-making to promote frequent and vigorous employee physical exercise. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Simultaneous ammonium and water recovery from landfill leachate using an integrated two-stage membrane distillation.

Resources recovery from landfill leachate (LFL) has been attracting growing attention instead of merely purifying the wastewater. An integrated two-stage membrane distillation (ITMD) was proposed to simultaneously purify LFL and recover ammonia in this study. The results showed that organics could be always effectively rejected by the ITMD regardless of varying feed pH, with COD removal higher than 99%. With feed pH increased from 8.64 to 12, the ammonia migration (50-100%) and capture (36-75%) in LFL were considerably enhanced, boosting the separated ammonia enrichment to 1.3-1.7 times due to the improved ammonium diffusion. However, the corresponding membrane flux of the first MD stage decreased from 13.7 to 10.5 L/m2·h. Elevating feed pH caused the deprotonation of NOM and its binding with inorganic ions, constituting a complex fouling layer on the membrane surface in the first MD stage. In contrast, the membrane permeability and fouling of the second MD were not affected by feed pH adjustment because only volatiles passed through the first MD. More importantly, it was estimated that ITMD could obtain high-quality water and recover high-purity ammonium from LFL with relatively low ammonium concentration at an input cost of $ 2-3/m3, which was very competitive with existing techniques. These results demonstrated that the ITMD can be a valuable candidate strategy for simultaneous water purification and nutrient recovery from landfill leachate.

A Study on the Gas/Humidity Sensitivity of the High-Frequency SAW CO Gas Sensor Based on Noble-Metal-Modified Metal Oxide Film.

In order to improve the response characteristics of the surface acoustic wave (SAW) sensor to trace gases, a SAW CO gas sensor based on a Pd-Pt/SnO2/Al2O3 film with a high-frequency response performance is proposed in this paper. The gas sensitivity and humidity sensitivity of trace CO gas are tested and analyzed under normal temperatures and pressures. The research results show that, compared with the frequency response of the Pd-Pt/SnO2 film, the CO gas sensor based on a Pd-Pt/SnO2/Al2O3 film has a higher frequency response performance, and the sensor has high-frequency response characteristics to CO gas with a concentration in the range of 10-100 ppm. The average response recovery time of 90% ranges from 33.4 s to 37.2 s, respectively. When the CO gas with a concentration of 30 ppm is tested repeatedly, its frequency fluctuation is less than 5%, indicating that the sensor has good stability. In the range of relative humidity (RH) from 25% to 75%, it also has high-frequency response characteristics for CO gas with a 20 ppm concentration.

A versatile genetic-encoded reporter for magnetic resonance imaging.

It has been a long-cherished wish in biomedicine research to have an imaging tool to visualize gene expression, with good spatiotemporal resolution, in rodent and primate animals noninvasively and longitudinally. To this purpose, we here present a novel genetic encoded magnetic resonance imaging reporter, i.e., GEM reporter, for noninvasive visualization of cell-specific gene expression. The GEM reporter was developed through codon modification of a bacteria-originated manganese (Mn) binding protein, allowing the sequestration of endogenous Mn in local tissues. When expressed in bacteria, plant and animals, GEM reporter can robustly produce high image contrast in T1-weighted MRI without additional substrates or contrast agents. Importantly, GEM reporter can be tracked inherently by MRI in specific cells and tissues. These findings support GEM reporter as a versatile marker for deciphering gene expression spatiotemporally in living subjects.

Study on SAW Methane Sensor Based on Cryptophane-A Composite Film.

Surface Acoustic Wave (SAW) methane-sensing technology is a new way to detect methane at room temperature. However, the material and structure of the sensitive film are the important factors affecting the detection performance of the sensor. In this paper-with a SAW methane sensor using graphene-nickel cavitation-a composite film is proposed, which can work at room temperature. A delay linear dual-channel differential oscillator with center frequency of 204.3 MHz and insertion loss of -5.658 dB was designed; Cryptophane-A material was prepared by the "three-step method". The composite sensitive film was synthesized by a drop coating method, electrochemical deposition method and electroplating method. The composite film was characterized by SEM. The sensor performance test system and gas sensitivity test system were constructed to determine the response performance of the sensor at concentrations of 0~5% CH4. The results showed that the sensor had a good response recovery performance in the test concentration range, and the frequency offset was positively correlated with methane concentration. The 90% average response time and recovery times were 41.2 s and 57 s, respectively. The sensor sensitivity was 809.4 ± 6.93 Hz/(1% CH4). This study provides a good theoretical basis for the development of surface acoustic-wave methane sensors.

CASPR2 antibody associated neurological syndromes in children.

To strengthen the understanding of the clinical features for CASPR2 neurological autoimmunity in children. A multicenter retrospective and prospective analysis of CASPR2 autoimmunity was conducted. Twenty-six patients were enrolled, including 25 with serum positivity and 3 with cerebrospinal fluid (CSF) positivity; 5 patients were co-positive with anti-NMDAR or anti-GABABR antibodies. Eleven patients (who manifested with refractory epilepsy, psychobehavioral abnormalities or germinoma) presented with low antibody titers, relatively normal MRI/EEG/CSF examinations, and poor response to immunotherapy and were thus considered false positive (42.3%). Fifteen patients were diagnosed with autoimmune encephalitis/ encephalopathy/ cerebellitis (including 1 whose condition was secondary to Japanese encephalitis). The most common symptoms included disorders of consciousness (10/15), fever (8/15), psychological symptoms/abnormal behaviors (8/15), sleep disorders (8/15), seizures (7/15), movement disorders (5/15), autonomic symptoms (5/15). Brain MRI revealed abnormalities in 10 patients (66.7%). Electroencephalography (EEG) recordings revealed a slow wave background in 13 patients (86.7%). Five patients showed elevated WBCs in CSF, and 4 patients showed elevated protein levels in the CSF. Thirteen patients received immunotherapy (rituximab was adopted in 2 cases) and recovered well. Two patients received symptomatic treatment, and the recovery was slow and accompanied by emotional abnormalities and developmental delay. Autoimmune encephalitis is the most common clinical phenotype; it can be secondary to Japanese encephalitis. Rituximab can be used in patients who respond poorly to conventional immunotherapy. The high false-positive rate of anti-CASPR2 in refractory epilepsy and the psychobehavioral abnormalities needs to be explored further.

All-trans retinoic acid enhances the cytotoxic effect of decitabine on myelodysplastic syndromes and acute myeloid leukaemia by activating the RARα-Nrf2 complex.

BACKGROUND: Decitabine (DAC) is used as the first-line therapy in patients with higher-risk myelodysplastic syndromes (HR-MDS) and elderly acute myeloid leukaemia (AML) patients unsuitable for intensive chemotherapy. However, the clinical outcomes of patients treated with DAC as a monotherapy are far from satisfactory. Adding all-trans retinoic acid (ATRA) to DAC reportedly benefitted MDS and elderly AML patients. However, the underlying mechanisms remain unclear and need further explorations from laboratory experiments. METHODS: We used MDS and AML cell lines and primary cells to evaluate the combined effects of DAC and ATRA as well as the underlying mechanisms. We used the MOLM-13-luciferase murine xenograft model to verify the enhanced cytotoxic effect of the drug combination. RESULTS: The combination treatment reduced the viability of MDS/AML cells in vitro, delayed leukaemia progress, and extended survival in murine xenograft models compared to non- and mono-drug treated models. DAC application as a single agent induced Nrf2 activation and downstream antioxidative response, and restrained reactive oxygen species (ROS) generation, thus leading to DAC resistance. The addition of ATRA blocked Nrf2 activation by activating the RARα-Nrf2 complex, leading to ROS accumulation and ROS-dependent cytotoxicity. CONCLUSIONS: These results demonstrate that combining DAC and ATRA has potential for the clinical treatment of HR-MDS/AML and merits further exploration.