Circadian patterns and photoperiodic modulation of clock gene expression and neuroendocrine hormone secretion in the marine teleost Larimichthys crocea.

The light/dark cycle, known as the photoperiod, plays a crucial role in influencing various physiological activities in fish, such as growth, feeding and reproduction. However, the underlying mechanisms of this influence are not fully understood. This study focuses on exploring the impact of different light regimes (LD: 12 h of light and 12 h of darkness; LL: 24 h of light and 0 h of darkness; DD: 0 h of light and 24 h of darkness) on the expression of clock genes (LcClocka, LcClockb, LcBmal, LcPer1, LcPer2) and the secretion of hormones (melatonin, GnRH, NPY) in the large yellow croaker, Larimichthys crocea. Real-time quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assays were utilized to assess how photoperiod variations affect clock gene expression and hormone secretion. The results indicate that changes in photoperiod can disrupt the rhythmic patterns of clock genes, leading to phase shifts and decreased expression. Particularly under LL conditions, the pineal LcClocka, LcBmal and LcPer1 genes lose their rhythmicity, while LcClockb and LcPer2 genes exhibit phase shifts, highlighting the importance of dark phase entrainment for maintaining rhythmicity. Additionally, altered photoperiod affects the neuroendocrine system of L. crocea. In comparison to the LD condition, LL and DD treatments showed a phase delay of GnRH secretion and an acceleration of NPY synthesis. These findings provide valuable insights into the regulatory patterns of circadian rhythms in fish and may contribute to optimizing the light environment in the L. crocea farming industry.

Light Management of Metal Halide Scintillators for High-Resolution X-Ray Imaging.

The ever-growing need to inspect matter with hyperfine structures requires a revolution in current scintillation detectors, and the innovation of scintillators is revived with luminescent metal halides entering the scene. Notably, for any scintillator, two fundamental issues arise: Which kind of material is suitable and in what form should the material exist? The answer to the former question involves the sequence of certain atoms into specific crystal structures that facilitate the conversion of X-ray into light, whereas the answer to the latter involves assembling these crystallites into particular material forms that can guide light propagation toward its corresponding pixel detector. Despite their equal importance, efforts are overwhelmingly devoted to improving the X-ray-to-light conversion, while the material-form-associated light propagation, which determines the optical signal collected for X-ray imaging, is largely overlooked. This perspective critically correlates the reported spatial resolution with the light-propagation behavior in each form of metal halides, combing the designing rules for their future development.

Circadian rhythm regulation in the sea cucumber Apostichopus japonicus: Insights into clock gene expression, photoperiod susceptibility, and neurohormone signaling.

Sea cucumber Apostichopus japonicus displays the typical circadian rhythms. This present study investigated the molecular regulation of clock genes, as well as monoamines and melatonin, in multiple tissues of A. japonicus, responding to the photoperiod. In order to determine their pivotal role in circadian rhythms, the crucial clock genes, namely AjClock, AjArnt1, AjCry1, and AjTimeless, were identified and a comprehensive analysis of their expressions across various tissues in adult A. japonicus was conducted, revealing the potential existence of central and peripheral oscillators. Results demonstrated that the tissues of polian vesicle and nerve ring exhibited significant clock gene expression associated with the orchestration of circadian regulation, and that environmental light fluctuations exerted influence on the expression of these clock genes. However, a number of genes, such as AjArnt1 and AjCry1, maintained their circadian rhythmicity even under continuous light conditions. Moreover, we further investigated the circadian patterns of melatonin (MT), serotonin (5-HT), and dopamine (DA) secretion in A. japonicus, data that underscored the tissue-specific regulatory differences and the inherent adaptability to dynamic light environments. Collectively, these findings will provide the molecular mechanisms controlling the circadian rhythm in echinoderms and the candidate tissues playing the role of central oscillators in sea cucumbers.

Synthesis and hybridization of CuInS2 nanocrystals for emerging applications.

Copper indium sulfide (CuInS2) is a ternary A(I)B(III)X(VI)2-type semiconductor featuring a direct bandgap with a high absorption coefficient. In attempts to explore their practical applications, nanoscale CuInS2 has been synthesized with crystal sizes down to the quantum confinement regime. The merits of CuInS2 nanocrystals (NCs) include wide emission tunability, a large Stokes shift, long decay time, and eco-friendliness, making them promising candidates in photoelectronics and photovoltaics. Over the past two decades, advances in wet-chemistry synthesis have achieved rational control over cation-anion reactivity during the preparation of colloidal CuInS2 NCs and post-synthesis cation exchange. The precise nano-synthesis coupled with a series of hybridization strategies has given birth to a library of CuInS2 NCs with highly customizable photophysical properties. This review article focuses on the recent development of CuInS2 NCs enabled by advanced synthetic and hybridization techniques. We show that the state-of-the-art CuInS2 NCs play significant roles in optoelectronic and biomedical applications.

Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study.

BACKGROUND: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments. METHODS: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1-18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended. FINDINGS: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6-10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37-41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89-100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4-20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66-91), duration of remission was 80% (68-92), and disease-free survival was 80% (68-92) with transplantation censoring; overall survival was 96% (91-100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7-14) after CD19-directed and 12 days (10-15) after CD22-directed CAR T-cell infusion. At data cutoff, 35 (45%) of 77 evaluable patients had CAR transgenes and 59 (77%) had B-cell aplasia. INTERPRETATION: This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition. FUNDING: The National Key Research & Development Program of China, the CAMS Innovation Fund for Medical Sciences (CIFMS), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Effects of Artificial Light at Night on Fitness-Related Traits of Sea Urchin (Heliocidaris crassispina).

Limited data are available regarding the effects of elevated coastal artificial light at night (ALAN) on intertidal echinoderms. In this study, we investigated the behavioral, morphological, and physiological responses of the sea urchin (Heliocidaris crassispina) after continuous exposure to ALAN at light intensities of 0.1, 300, and 600 Lux for 6 weeks. Our findings revealed that ALAN at 300 Lux substantially reduced food consumption, Lantern weight, and gonadosomatic index (GSI). On the other hand, ALAN at 600 Lux notably prolonged the righting and covering response times and elevated the 5-HIAA/5-HT ratio, while concurrently decreasing food consumption, body weight, Lantern weight, GSI, and Pax6 gene expression. These results indicated that continuous exposure to ALAN could cause an adverse effect on fitness-related traits, including behavioral responses, growth, reproductive performance, and photoreception of sea urchins. The present study provides new insights on the impact of light pollution on echinoderms.

Comparative transcriptome analysis reveals key genes and pathways related to gonad development in the sea cucumber Apostichopus japonicus.

The sea cucumber Apostichopus japonicus is an economically important marine species in China, and understanding the mechanisms underlying its gonad development is crucial for successful reproduction and breeding. In this study, we performed transcriptome comparisons and analyses of A. japonicus gonadal and non-gonadal tissues to identify genes and molecular pathways associated with gonadal development. We also supplemented the annotation of the A. japonicus genome. Collectively, results revealed a total of 941 ovary-specific genes and 2499 testis-specific genes through different expression analysis and WGCNA analysis. The most enriched pathways in ovary and testis were "DNA replication" and "purine metabolism", respectively. Additionally, we identified key candidate gene modules that control gonad development and germ cell maturation, with CDT1 and DYNC2LI1 serving as hub genes. Our findings provide important insights into the gonadal development system of A. japonicus and offer valuable references for further research on reproductive biology in this marine invertebrate species.

Melatonin modulates the hypothalamic-pituitary neuroendocrine axis to regulate physiological color change in teleost fish.

Melatonin (MT) is a crucial neuroendocrine regulator of various physiological activities in vertebrates, especially in circadian or seasonal rhythm control. In the present study, the large yellow croaker (Larimichthys crocea), a marine bony fish with circadian body color change behavior, is chosen for functional investigation on teleost MT signaling systems that remain uncharacterized. All five melatonin receptors (LcMtnr1a1, LcMtnr1a2, LcMtnr1b1, LcMtnr1b2, and LcMtnr1c) were significantly activated by MT, triggering extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation through different G protein coupling signaling pathways, with exclusive Gαi-dependency for LcMtnr1a2 and LcMtnr1c, and Gαq-dependency for two LcMtnr1b paralogs, whereas LcMtnr1a1 activated Gαi and Gαs dual-dependent signaling pathways. A comprehensive model of the MT signaling system in the hypothalamic-pituitary neuroendocrine axis was further constructed based on ligand-receptor interaction analysis using single-cell RNA-seq data, as well as spatial expression patterns of Mtnrs and related neuropeptides in central neuroendocrine tissues. A novel regulatory pathway of MT/melanin-concentrating hormone (MCH) and MT/(tachykinin precursor 1 (TAC1)+corticotropin-releasing hormone (CRH))/melanocyte-stimulating hormone (MSH) was discovered that functions in chromatophore mobilization and physiological color change and was further validated by pharmacological experiments. Together, our findings define multiple intracellular signaling pathways mediated by L. crocea melatonin receptors and provide the first in-depth evidence that uncover the upstream modulating roles of the MT signaling system in the hypothalamic-pituitary neuroendocrine axis of a marine teleost species, particularly in chromatophore mobilization and physiological color change.

Bisphenol A (BPA) Directly Activates the G Protein-Coupled Estrogen Receptor 1 and Triggers the Metabolic Disruption in the Gonadal Tissue of Apostichopus japonicus.

The sea cucumber, Apostichopus japonicus, is a marine benthic organism that feeds on small benthic particulate matter and is easily affected by pollutants. Bisphenol A (BPA, 4,4'-isopropylidenediphenol) has been identified as an endocrine disruptor. It is ubiquitously detectable in oceans and affects a variety of marine animals. It functions as an estrogen analog and typically causes reproductive toxicity by interfering with the endocrine system. To comparatively analyze the reproductive effects of estradiol (E2) and BPA on sea cucumbers, we identified a G protein-coupled estrogen receptor 1 (GPER1) in A. japonicus and investigated its effects on reproduction. The results showed that BPA and E2 exposure activated A. japonicus AjGPER1, thereby mediating the mitogen-activated protein kinase signaling pathways. High-level expression of AjGPER1 in the ovarian tissue was confirmed by qPCR. Furthermore, metabolic changes were induced by 100 nM (22.83 µg/L) BPA exposure in the ovarian tissue, leading to a notable increase in the activities of trehalase and phosphofructokinase. Overall, our findings suggest that AjGPER1 is directly activated by BPA and affects sea cucumber reproduction by disrupting ovarian tissue metabolism, suggesting that marine pollutants pose a threat to the conservation of sea cucumber resources.

Long-term follow-up of donor-derived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia.

BACKGROUND: Donor-derived CD7-directed chimeric antigen receptor (CAR) T cells showed feasibility and early efficacy in patients with refractory or relapsed T-cell acute lymphoblastic leukemia (r/r T-ALL), in a previous phase I trial report, at a median follow-up of 6.3 months. Here we report long-term safety and activity of the therapy after a 2-year follow-up. METHODS: Participants received CD7-directed CAR T cells derived from prior stem cell transplantation (SCT) donors or from HLA-matched new donors after lymphodepletion. The target dose was 1 × 106 (± 30%) CAR T cells per kg of patient weight. The primary endpoint was safety with efficacy secondary. This report focuses on the long-term follow-up and discusses them in the context of previously reported early outcomes. RESULTS: Twenty participants were enrolled and received infusion with CD7 CAR T cells. After a median follow-up time of 27.0 (range, 24.0-29.3) months, the overall response rate and complete response rate were 95% (19/20 patients) and 85% (17/20 patients), respectively, and 35% (7/20) of patients proceeded to SCT. Six patients experienced disease relapse with a median time-to-relapse of 6 (range, 4.0-10.9) months, and 4 of these 6 patients were found to have lost CD7 expression on tumor cells. Progression-free survival (PFS) and overall survival (OS) rates 24 months after treatment were respectively 36.8% (95% CI, 13.8-59.8%) and 42.3% (95% CI, 18.8-65.8%), with median PFS and OS of respectively 11.0 (95% CI, 6.7-12.5) months and 18.3 (95% CI, 12.5-20.8) months. Previously reported short-term adverse events (< 30 days after treatment) included grade 3-4 cytokine release syndrome (CRS; 10%) and grade 1-2 graft-versus-host disease (GVHD; 60%). Serious adverse events reported > 30 days after treatment included five infections and one grade 4 intestinal GVHD. Despite good CD7 CAR T-cell persistence, non-CAR T and natural killer cells were predominantly CD7-negative and eventually returned to normal levels in about half of the participants. CONCLUSIONS: In this 2-year follow-up analysis, donor-derived CD7 CAR T-cell treatment demonstrated durable efficacy in a subset of patients with r/r T-ALL. Disease relapse was the main cause of treatment failure, and severe infection was a noteworthy late-onset adverse event. TRIAL REGISTRATION: ChiCTR2000034762.

A Heat-Liquefiable Solid Precursor for Ambient Growth of Perovskites with High Tunability, Performance and Stability.

Halide perovskites are intensively studied for applications in optoelectronic devices because of their outstanding properties and relatively low cost. However, the common precursor solutions for perovskite fabrication are rather unstable in the presence of moisture and oxygen, limiting the large-scale low-cost production of perovskite. Herein, water is used counterintuitively to formulate an ambient stable perovskite precursor, which is peculiar in that it is solid at room temperature but becomes a liquid at 75 °C. The non-fluidity of the precursor stemmed from the water-assisted intermediate fiber assembly, conferring high damp air stability. Yet the heat-liquefiability made the precursor highly processible for perovskite growth, and when guided by polyvinyl pyrrolidone coordination with Pb2+ , the perovskite can preferentially grow along the [200] direction, significantly improving the film quality. To demonstrate the utility of the precursor, it has been used to fabricate self-driven halide perovskite photodetectors, which exhibited a low noise current of 2.0 × 10-14  A Hz-1/2 , a high specific detectivity up to 1.4 × 1013 Jones, and high stability of 20 days of operation with only < 5% external quantum efficiency decay. This type of solid-liquid convertible precursor opens up new opportunities for wider applications of perovskites.

Sequential Growth of 2D/3D Double-Layer Perovskite Films with Superior X-Ray Detection Performance.

Perovskite materials in different dimensions show great potential in direct X-ray detection, but each with limitations stemming from its own intrinsic properties. Particularly, the sensitivity of two-dimensional (2D) perovskites is limited by poor carrier transport while ion migration in three-dimensional (3D) perovskites causes the baseline drifting problem. To circumvent these limitations, herein a double-layer perovskite film is developed with properly aligned energy level, where 2D (PEA)2 MA3 Pb4 I13 (PEA=2-phenylethylammonium, MA=methylammonium) is cascaded with vertically crystallized 3D MAPbI3 . In this new design paradigm, the 3D layer ensures fast carrier transport while the 2D layer mitigates ion migration, thus offering a high sensitivity and a greatly stabilized baseline. Besides, the 2D layer increases the film resistivity and enlarges the energy barrier for hole injection without compromising carrier extraction. Consequently, the double-layer perovskite detector delivers a high sensitivity (1.95 × 104 µC Gyair -1 cm-2 ) and a low detection limit (480 nGyair s-1 ). Also demonstrated is the X-ray imaging capacity using a circuit board as the object. This work opens up a new avenue for enhancing X-ray detection performance via cascade assembly of various perovskites with complementary properties.

Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial.

PURPOSE: Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (r/r T-ALL) have few options and poor prognosis. The aim was to assess donor-derived anti-CD7 chimeric antigen receptor (CAR) T-cell safety and efficacy in patients with r/r T-ALL. METHODS: In this single-center, phase I trial, we administered anti-CD7 CAR T cells, manufactured from either previous stem-cell transplantation donors or new donors, to patients with r/r T-ALL, in single infusions at doses of 5 × 105 or 1 × 106 (±30%) cells per kilogram of body weight. The primary end point was safety with efficacy secondary. RESULTS: Twenty participants received infusions. Adverse events including cytokine release syndrome grade 1-2 occurred in 90% (n = 18) and grade 3-4 in 10% (n = 2), cytopenia grade 3-4 in 100% (n = 20), neurotoxicity grade 1-2 in 15% (n = 3), graft-versus-host disease grade 1-2 in 60% (n = 12), and viral activation grade 1-2 in 20% (n = 4). All adverse events were reversible, except in one patient who died through pulmonary hemorrhage related to fungal pneumonia, which occurred at 5.5 months, postinfusion. Ninety percent (n = 18) achieved complete remission with seven patients proceeding to stem-cell transplantation. At a median follow-up of 6.3 months (range, 4.0-9.2), 15 remained in remission. CAR T cells were still detectable in five of five patients assessed in month 6, postinfusion. Although patients' CD7-positive normal T cells were depleted, CD7-negative T cells expanded and likely alleviated treatment-related T-cell immunodeficiency. CONCLUSION: Among 20 patients with r/r T-ALL enrolled in this trial, donor-derived CD7 CAR T cells exhibited efficient expansion and achieved a high complete remission rate with manageable safety profile. A multicenter, phase II trial of donor-derived CD7 CAR T cells is in progress (NCT04689659).

Molecular identification of an androgen receptor and the influence of long-term aggressive interaction on hypothalamic genes expression in black rockfish (Sebastes schlegelii).

This study aims to explore the mechanism on how aggressive interaction alters reproductive physiology by testing whether aggressive interaction can activate the reproductive neuroendocrine function via the hypothalamus-pituitary-gonadal (HPG) axis in black rockfish (Sebastes schlegelii). The expressions of the androgen receptor gene (ar) and gonadotropin-releasing hormone genes (gnrhs), the concentration of plasma androgens, and GSI (the ratio of testes mass to body mass) were compared between the interaction group (dominant males or subordinate males) and the isolation group in male black rockfish after 3 weeks. A full-length cDNA encoding an androgen receptor (AR) of 766 amino acids was isolated. Transcripts encoding this AR were detected at a high relative abundance in the liver, kidney, testis, ovary, muscle, and intestine tissue. Further evaluation of brain genes transcripts abundance revealed that the mRNA levels of gnrh I and ar genes were significantly different between the interaction group and the isolation group in the hypothalamus. However, no significant difference was detected in testosterone, 11-keto-testosterone, and GSI between these two groups. This study indicates that a long-term aggressive interaction affect the expression of hypothalamic gnrh I and ar but may not change the physiological function of the HPG axis in an all-male condition.

Self-Driven Perovskite Narrowband Photodetectors with Tunable Spectral Responses.

Narrowband photodetectors with tunable spectral responses are highly desirable for applications in image sensing, machine vision, and optical communication. Herein, a filterless and self-driven perovskite narrowband photodetector (PNPD) based on the defect-assisted charge collection narrowing (CCN) mechanism is reported, which is enabled by a high-quality thick perovskite film. By adjusting the halide component of the perovskite layer, the bandgap is successfully modulated and the corresponding narrowband photodetectors show a wide spectral response range from the red to the near-infrared (NIR), all with full-widths at half maximum (FWHMs) below 30 nm. Specifically, the methylammonium lead iodide (MAPbI3 ) narrowband photodetector exhibits a characteristic detection peak at 800 nm with a very low noise current of ≈0.02 pA Hz-1/2 , a high specific detectivity up to 1.27 × 1012 Jones, and a fast response speed with rise/fall time of 12.7/6.9 µs. Impressively, these values are among the highest of their kind reported previously, and allow demonstration of narrowband imaging. The excellent performance of self-driven PNPDs lights up their prospect in high-efficiency optoelectronic devices without external power sources.

Changes in Aggressive Behavior, Cortisol and Brain Monoamines during the Formation of Social Hierarchy in Black Rockfish (Sebastes schlegelii).

Aggressive interactions can lead to a social hierarchy and influence the responses of animal behavior and physiology. However, our understanding on the changes of fish behavior and physiology during the process of social hierarchical formation is limited. To explore the responses of fish behavior and physiology to social hierarchy, we examined the differences in the growth performance, aggression, cortisol level, brain serotonergic activity, and brain dopamine activity between the dominant individuals and the subordinate individuals of black rockfish (Sebastes schlegelii) in two time scenarios. In the short-term contest, the cortisol level and the ratio of telencephalic 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) was significantly higher in subordinate individuals than in dominant individuals. In the long-term contest, the ratios of 5-HIAA/5-HT in all brain regions were significantly higher, and the frequency of aggressive acts were significantly lower in subordinate individuals than in dominant individuals. In contrast, no difference was detected in growth performance. Significant positive correlations between the cortisol level and serotonergic activity were observed in the short-term contest, but the serotonergic activity was negatively correlated with the aggressive behavior in the long-term contest. These results suggest that subordinate hierarchy inhibits aggression but does not impact growth in black rockfish. The cortisol-related change in brain monoaminergic activity could be a potential indicator to predict aggressive behavior in black rockfish in captivity with an obvious social hierarchy.

Mutations in the BCR-ABL1 kinase domain in patients with chronic myeloid leukaemia treated with TKIs or at diagnosis.

The aim of the present study was to analyse the incidence of mutations in the BCR-ABL1 kinase region in patients with newly diagnosed or treated chronic myeloid leukaemia (CML), and the association between mutations clinicopathological characteristics. Samples were collected for mutation analysis from patients who exhibited tyrosine kinase inhibitor resistance following treatment or were in the accelerated or blast phase at diagnosis. The mutations in the breakpoint cluster region (BCR)-ABL proto-oncogene 1 (ABL1) kinase domain were evaluated using conventional sequencing or ultra-deep sequencing (UDS) of peripheral blood samples. Sanger sequencing and UDS of the cDNA region corresponding to the BCR-ABL1 kinase domain was performed. χ2 test was used to assess the association of categorical variables between the mutated and non-mutated groups. In addition, the Kaplan-Meier method was applied to generate the survival curves. Sequencing detected 28 different mutations in 54 of the 175 (30.86%) patients with CML. A total of 14 (8.0%) patients presented with the T315I mutation, accounting for the largest proportion in the mutated group. Eight patients (4.6%) presented with more than one mutation, three (37.5%) of whom harboured T315I coexisting with other mutations, and for nine (5.1%) patients, the results differed between conventional sequencing and UDS, with the mutations being missed by conventional sequencing. The results form this study suggested that programing mutation analysis in patients with chronic myeloid leukaemia timely may guide the choice of TKIs.

Study of the association of seventeen single nucleotide polymorphisms and their haplotypes in the TNF-α, IL-2, IL-4 and IL-10 genes with the antibody response to inactivated Japanese encephalitis vaccine.

To investigate whether the TNF-α, IL-2, IL-4 and IL-10 genes contribute to variations in vaccine-induced immune responses after immunization with the inactivated Japanese encephalitis vaccine (IJEV), a total of 369 individuals who received the IJEV were enrolled. Based on Japanese encephalitis virus (JEV) neutralization antibodies (NAbs), the individuals were divided into seropositive (SP) and seronegative (SN) groups. Then, 17 SNPs in the TNF-α, IL-2, IL-4 and IL-10 genes were genotyped using the TaqMan method. Although there was no association of the TNF-α, IL-2, IL-4 and IL-10 genes with JEV seropositivity triggered by JEV vaccination when all the individuals in the SP and SN groups were compared, differences were observed in a subgroup analysis. In the male group, rs2243291 in the IL-4 gene showed a difference between the JEV SP and SN groups with the overdominant model (P = .045), and the C/G genotypes conferred more JEV seropositivity (OR = 1.87; 95% CI: 1.01-3.49); the CT genotype of rs3093726 in the TNF-α gene showed higher JEV NAbs geometric mean titer (GMT) than the TT genotype (P = .018, CT: 1.677 ± 0.144 vs TT: 1.271 ± 0.039). Furthermore, the rs1800629 genotype in the TNF-α gene and the rs1800896 genotype in the IL-10 gene exhibited a trend of association with JEV seropositivity in the female group, but the difference was not significant. The present study suggested that the polymorphisms in the cytokine genes could be associated with sex-specific JEV NAbs seroconversion. However, more samples should be studied, and further functional verification should be performed.

FA-Assistant Iodide Coordination in Organic-Inorganic Wide-Bandgap Perovskite with Mixed Halides.

Mixed-halide wide-bandgap perovskites are key components for the development of high-efficiency tandem structured devices. However, mixed-halide perovskites usually suffer from phase-impurity and high defect density issues, where the causes are still unclear. By using in situ photoluminescence (PL) spectroscopy, it is found that in methylammonium (MA+ )-based mixed-halide perovskites, MAPb(I0.6 Br0.4 )3 , the halide composition of the spin-coated perovskite films is preferentially dominated by the bromide ions (Br- ). Additional thermal energy is required to initiate the insertion of iodide ions (I- ) to achieve the stoichiometric balance. Notably, by incorporating a small amount of formamidinium ions (FA+ ) in the precursor solution, it can effectively facilitate the I- coordination in the perovskite framework during the spin-coating and improve the composition homogeneity of the initial small particles. The aggregation of these homogenous small particles is found to be essential to achieve uniform and high-crystallinity perovskite film with high Br- content. As a result, high-quality MA0.9 FA0.1 Pb(I0.6 Br0.4 )3 perovskite film with a bandgap (Eg ) of 1.81 eV is achieved, along with an encouraging power-conversion-efficiency of 17.1% and open-circuit voltage (Voc ) of 1.21 V. This work also demonstrates the in situ PL can provide a direct observation of the dynamic of ion coordination during the perovskite crystallization.