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Glassy hybrid metal halides have emerged as promising materials in recent years due to their high structural adjustability and low melting points, offering unique merits that overcome the limitations of their crystalline and polycrystalline counterparts as well as other conventional amorphous semiconductors. This review article comprehensively explores the structural characteristics, electronic properties, and chemical coordination of hybrid metal halides, emphasizing their role in the glass transition from the crystalline phase to the amorphous phase. We examine the intrinsic disorder within the amorphous phase that facilitates light transmission and discuss recent advances in device architecture and interface engineering by optimizing the charge transport of glassy hybrid metal halides for high-quality applications. With full theoretical understanding and rational structural design, potential applications in displays, information storage, X-ray imaging, and sensing are highlighted, underscoring the transformative impact of glassy hybrid metal halides in the fields of materials science and information science.

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)2MA3Pb4I13 (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. By integrating a layered 2D perovskite with a vertically crystallized MAPbI3, a double‐layer perovskite is constructed for direct X‐ray detection, showing stable baseline, a high sensitivity of 19 503 μC Gyair−1 cm−2, and a low detection limit of 480 nGyair s−1. This work provides a strategy to unlock the performance limitations stemming from the intrinsic properties of the perovskite.

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 × 10 6 (± 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.

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. 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. 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. 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. 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. For the Chinese translation of the abstract see Supplementary Materials section.

Chimeric antigen receptor (CAR) T cells show suboptimal efficacy in acute myeloid leukemia (AML). We find that CAR T cells exposed to myeloid leukemia show impaired activation and cytolytic function, accompanied by impaired antigen receptor downstream calcium, ZAP70, ERK, and C-JUN signaling, compared to those exposed to B-cell leukemia. These defects are caused in part by the high expression of CD155 by AML. Overexpressing C-JUN, but not other antigen receptor downstream components, maximally restores anti-tumor function. C-JUN overexpression increases costimulatory molecules and cytokines through reinvigoration of ERK or transcriptional activation, independent of anti-exhaustion. We conduct an open-label, non-randomized, single-arm, phase I trial of C-JUN-overexpressing CAR-T in AML (NCT04835519) with safety and efficacy as primary and secondary endpoints, respectively. Of the four patients treated, one has grade 4 (dose-limiting toxicity) and three have grade 1–2 cytokine release syndrome. Two patients have no detectable bone marrow blasts and one patient has blast reduction after treatment. Thus, overexpressing C-JUN endows CAR-T efficacy in AML. Chimeric Antigen Receptor (CAR)-T cells show suboptimal efficacy in Acute Myeloid Leukaemia (AML). Here, the authors show that overexpression of C-JUN improves CAR-T cells efficacy in preclinical models for AML and report preliminary results of a pilot phase I clinical trial.

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.

Background Severe combined immunodeficiency(SCID) combined with Bacillus Calmette-Guérin(BCG) disease(BCG-osis) is a rare but life-threatening complication in pediatric patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early recognition and intervention are essential to prevent severe complications. Case presentation We have described two pediatric cases of SCID combined with BCG-osis in which the patients received salvage therapy with allo-HSCT. Data were collected from two male infants who underwent allo-HSCT for SCID with BCG-osis at Wuhan Children’s Hospital between January 2017 and December 2022. The data of the two patients were retrospectively collected and analyzed to summarize their clinical characteristics, treatment, and prognosis. Patient 1 presented with SCID combined with disseminated BCG-osis and underwent HSCT after only 30 days of anti-tuberculosis therapy. The tuberculosis infection recurred at 83 days after transplantation, and the patient eventually died of multi-organ failure and disseminated intravascular coagulation. Patient 2 presented with SCID combined with disseminated BCG-osis after HSCT. The patient responded well to antituberculosis drugs and successfully completed a year and a half of anti-tuberculosis treatment. On day 591 post-transplant, the anti-tuberculosis regimen was discontinued in this patient. Conclusions Patients with SCID have severe defects in cellular and humoral immunity. Genetic screening at birth would help identify such patients, and the BCG vaccination should be delayed in such cases. The sole curative option for SCID is HSCT, which can achieve immune reconstitution when performed early on and can improve the survival rate.

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.

Dojo loach, Misgurnus anguillicaudatus is a freshwater fish species of the loach family Cobitidae, using its posterior intestine as an accessory air-breathing organ. Little is known about the molecular regulatory mechanisms in the formation of intestinal air-breathing function of M. anguillicaudatus . Here high-throughput sequencing of mRNAs was performed from six developmental stages of posterior intestine of M. anguillicaudatus : 4-Dph (days post hatch) group, 8-Dph group, 12-Dph group, 20-Dph group, 40-Dph group and Oyd (one-year-old) group. These six libraries were assembled into 81300 unigenes. Totally 40757 unigenes were annotated. Subsequently, 35291 differentially expressed genes (DEGs) were scanned among different developmental stages and clustered into 20 gene expression profiles. Finally, 15 key pathways and 25 key genes were mined, providing potential targets for candidate gene selection involved in formation of intestinal air-breathing function in M. anguillicaudatus . This is the first report of developmental transcriptome of posterior intestine in M. anguillicaudatus , offering a substantial contribution to the sequence resources for this species and providing a deep insight into the formation mechanism of its intestinal air-breathing function. This report demonstrates that M. anguillicaudatus is a good model for studies to identify and characterize the molecular basis of accessory air-breathing organ development in fish.

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.