Acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) is a haematological malignancy characterized by the uncontrolled proliferation of immature lymphoid cells. Over past decades, significant progress has been made in understanding the biology of ALL, resulting in remarkable improvements in its diagnosis, treatment and monitoring. Since the advent of chemotherapy, ALL has been the platform to test for innovative approaches applicable to cancer in general. For example, the advent of omics medicine has led to a deeper understanding of the molecular and genetic features that underpin ALL. Innovations in genomic profiling techniques have identified specific genetic alterations and mutations that drive ALL, inspiring new therapies. Targeted agents, such as tyrosine kinase inhibitors and immunotherapies, have shown promising results in subgroups of patients while minimizing adverse effects. Furthermore, the development of chimeric antigen receptor T cell therapy represents a breakthrough in ALL treatment, resulting in remarkable responses and potential long-term remissions. Advances are not limited to treatment modalities alone. Measurable residual disease monitoring and ex vivo drug response profiling screening have provided earlier detection of disease relapse and identification of exceptional responders, enabling clinicians to adjust treatment strategies for individual patients. Decades of supportive and prophylactic care have improved the management of treatment-related complications, enhancing the quality of life for patients with ALL.

MiR-34a-5p suppresses cutaneous squamous cell carcinoma progression by targeting SIRT6.

Cutaneous squamous cell carcinoma (cSCC) is a malignant tumor originating from epidermal or appendageal keratinocytes, with a rising incidence in recent years. Understanding the molecular mechanism driving its development is crucial. This study aims to investigate whether miR-34a-5p is involved in the pathogenesis of cSCC by targeting Sirtuin 6 (SIRT6).The expression levels of miR-34a-5p and SIRT6 were determined in 15 cSCC tissue specimens, 15 normal tissue specimens and cultured cells via real-time polymerase chain reaction (RT-qPCR). Pearson's correlation analysis was conducted to evaluate the relationship between miR-34a-5p and SIRT6 expression levels in cSCC tissues. A431 and SCL-1 cells were transfected with miR-34a-5p mimic, negative control or miR-34a-5p mimic together with recombinant plasmids containing SIRT6 gene. Cell counting kit-8, clone formation assay, wound healing assay, and flow cytometry were employed to assess the effects of these transfections on proliferation, migration, and apoptosis, respectively. The interaction between miR-34a-5p and SIRT6 was characterized using a dual-luciferase reporter assay.MiR-34a-5p expression was down-regulated in cSCC tissues significantly, while the SIRT6 expression was the opposite. A negative correlation was observed between the expression of miR-34a-5p and SIRT6 in cSCC tissues. Furthermore, overexpression of miR-34a-5p led to a significant reduction in the proliferation and migration abilities of A431 and SCL-1 cells, accompanied by an increase in apoptosis levels and a decrease in SIRT6 expression levels. MiR-34a-5p was identified as a direct target of SIRT6. Importantly, overexpression of SIRT6 effectively counteracted the inhibitory effect mediated by miR-34a-5p in cSCC cells.Our findings suggest that miR-34a-5p functions as a tumor suppressor in cSCC cells by targeting SIRT6.

Atomically dispersed MoNi alloy catalyst for partial oxidation of methane.

The catalytic partial oxidation of methane (POM) presents a promising technology for synthesizing syngas. However, it faces severe over-oxidation over catalyst surface. Attempts to modify metal surfaces by incorporating a secondary metal towards C-H bond activation of CH4 with moderate O* adsorption have remained the subject of intense research yet challenging. Herein, we report that high catalytic performance for POM can be achieved by the regulation of O* occupation in the atomically dispersed (AD) MoNi alloy, with over 95% CH4 conversion and 97% syngas selectivity at 800 °C. The combination of ex-situ/in-situ characterizations, kinetic analysis and DFT (density functional theory) calculations reveal that Mo-Ni dual sites in AD MoNi alloy afford the declined O2 poisoning on Ni sites with rarely weaken CH4 activation for partial oxidation pathway following the combustion reforming reaction (CRR) mechanism. These results underscore the effectiveness of CH4 turnovers by the design of atomically dispersed alloys with tunable O* adsorption.

Higher dietary live microbe intake is associated with a lower risk of sarcopenia.

OBJECTIVE: This study aimed to investigate the potential association between dietary live microbe intake and sarcopenia. METHODS: Data from 5368 participants were gathered from the National Health and Nutrition Examination Survey (NHANES). Dietary information was assessed using a self-report questionnaire. The participants were categorized into low, medium, and high dietary live microbe groups. Sarcopenia was defined according to the National Institutes of Health (NIH) definition (appendicular skeletal muscle mass/body mass index <0.789 for men and <0.512 for women). Multivariate regression analysis and stratified analyses were performed. RESULTS: After adjusting for potential confounding factors, individuals in the high dietary live microbe group exhibited a lower prevalence of sarcopenia compared to those in the low dietary live microbe group. The adjusted odds ratio (with 95% confidence intervals) was 0.63 (0.44-0.89) (p for trend <0.05). Subgroup analyses indicated a potential difference in the impact of dietary live microbe intake on sarcopenia between individuals with and without diabetes (p for interaction = 0.094). CONCLUSION: Higher dietary live microbe intake was associated with a lower risk of sarcopenia.

SMARCA5 reprograms AKR1B1-mediated fructose metabolism to control leukemogenesis.

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.

Chronic increasing nitrogen and endogenous phosphorus release from sediment threaten to the water quality in a semi-humid region reservoir.

The water quality in the drinking water reservoir directly affects people's quality of life and health. When external pollution input is effectively controlled, endogenous release is considered the main cause of water quality deterioration. As the major nitrogen (N) and phosphorus (P) sources in reservoirs, sediment plays a vital role in affecting the water quality. To understand the spatial and temporal variation of N and P in the sediment, this study analyzed the current characteristics and cumulative effects of a semi-humid reservoir, Yuqiao Reservoir, in North China. The N and P concentrations in the reservoir sediment were decreased along the flow direction, while the minimum values were recorded at the central sediment profile. External input and algal deposition were the main factors leading to higher sediment concentrations in the east (Re-E) and west (Re-W) areas of reservoir sediment profiles. According to the long-term datasets, the peaks of both sediment total nitrogen content and deposition rate were observed in the 2010s, which has increased about three times and six times than in the1990s, respectively. Therefore, the increase in phosphorus concentration may be the main reason for eutrophication in water in recent years. The mineralization of organic matter has a significant promoting effect on releasing N and P from sediments, which will intensify eutrophication in water dominated by P and bring huge challenges to water environment management. This study highlights that the current imbalance in N and P inputs into reservoirs and the endogenous P release from sediment will have a significant impact on water quality.

Key clinical predictors in the diagnosis of ovarian torsion in children.

OBJECTIVE: Ovarian torsion (OT) represents a severe gynecological emergency in female pediatric patients, necessitating immediate surgical intervention to prevent ovarian ischemia and preserve fertility. Prompt diagnosis is, therefore, paramount. This retrospective study set out to assess the utility of combined clinical, ultrasound, and laboratory features in diagnosing OT. METHODS: The authors included 326 female pediatric patients aged under 14 years who underwent surgical confirmation of OT over a five-year period. Logistic regression analysis was employed to pinpoint factors linked with OT, and the authors compared clinical presentation, laboratory results, and ultrasound characteristics between patients with OT (OT group) and without OT (N-OT group). The authors conducted receiver operating characteristic (ROC) curve analysis to gauge the predictive capacity of the combined features. RESULTS: Among 326, OT was confirmed in 24.23 % (79 cases) of the patients. The OT group had a higher incidence of prenatal ovarian masses than the N-OT (22 cases versus 7 cases) (p < 0.0001). Similarly, the authors observed significant differences in the presence of lower abdominal pain, suspected torsion on transabdominal ultrasound, and a high neutrophil-lymphocyte ratio (NLR > 3) between the OT and non-OT groups (p ˂ 0.05). Furthermore, when these parameters were combined, the resulting area under the curve (AUC) was 0.868, demonstrating their potential utility in OT diagnosis. CONCLUSION: This study demonstrates a prediction model integrating clinical, laboratory, and ultrasound findings that can support the preoperative diagnosis of ovarian torsion, thereby enhancing diagnostic precision and improving patient management. Future prospective studies should concentrate on developing clinical predictive models for OT in pediatric patients.

Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial.

BACKGROUND: The autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M has been approved for the treatment of relapsed and refractory multiple myeloma in many countries across the world under the name ciltacabtagene autoleucel. LEGEND-2 was the first-in-human trial of LCAR-B38M and yielded deep and durable therapeutic responses. Here, we reported the outcomes in LEGEND-2 after a minimal 5-year follow-up. METHODS: Participants received an average dose of 0.5 × 106 cells/kg LCAR-B38M in split or single unfractionated infusions after cyclophosphamide-based lymphodepletion therapy. Investigator-assessed response, survival, safety and pharmacokinetics were evaluated. RESULTS: Seventy-four participants enrolled and had a median follow-up of 65.4 months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 21.0% and 49.1%, with progressive flattening of the survival curves over time. Patients with complete response (CR) had longer PFS and OS, with 5-year rates of 28.4% and 65.7%, respectively. Twelve patients (16.2%) remained relapse-free irrespective of baseline high-risk cytogenetic abnormality and all had normal humoral immunity reconstituted. An ongoing CR closely correlated with several prognostic baseline indices including favorable performance status, immunoglobulin G subtype, and absence of extramedullary disease, as well as a combination cyclophosphamide and fludarabine preconditioning strategy. Sixty-two (83.8%) suffered progressive disease (PD) and/or death; however, 61.1% of PD patients could well respond to subsequent therapies, among which, the proteasome inhibitor-based regimens benefited the most. Concerning the safety, hematologic and hepatic function recovery were not significantly different between non-PD and PD/Death groups. A low rate of second primary malignancy (5.4%) and no severe virus infection were observed. The patients who tested positive for COVID-19 merely presented self-limiting symptoms. In addition, a sustainable CAR T population of one case with persistent remission was delineated, which was enriched with indolently proliferative and lowly cytotoxic CD4/CD8 double-negative functional T lymphocytes. CONCLUSIONS: These data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma. TRIAL REGISTRATION: LEGEND-2 was registered under the trial numbers NCT03090659, ChiCTRONH-17012285.

Nitrogen-doped titanium dioxide/schwertmannite nanocomposites as heterogeneous photo-Fenton catalysts with enhanced efficiency for the degradation of bisphenol A.

Potential health risks related to environmental endocrine disruptors (EEDs) have aroused research hotspots at the forefront of water treatment technologies. Herein, nitrogen-doped titanium dioxide/schwertmannite nanocomposites (N-TiO2/SCH) have been successfully developed as heterogeneous catalysts for the degradation of typical EEDs via photo-Fenton processes. Due to the sustainable Fe(III)/Fe(II) conversion induced by photoelectrons, as-prepared N-TiO2/SCH nanocomposites exhibit much enhanced efficiency for the degradation of bisphenol A (BPA; ca. 100% within 60 min under visible irradiation) in a wide pH range of 3.0-7.8, which is significantly higher than that of the pristine schwertmannite (ca. 74.5%) or N-TiO2 (ca. 10.8%). In this photo-Fenton system, the efficient degradation of BPA is mainly attributed to the oxidation by hydroxyl radical (•OH) and singlet oxygen (1O2). Moreover, the possible catalytic mechanisms and reaction pathway of BPA degradation are systematically investigated based on analytical and photoelectrochemical analyses. This work not only provides a feasible means for the development of novel heterogeneous photo-Fenton catalysts, but also lays a theoretical foundation for the potential application of mineral-based materials in wastewater treatment.

Expression analysis and biological regulation of silencing regulatory protein 6 (SIRT6) in cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer worldwide. Therefore, the identification of biomarkers associated with CSCC progression could aid in the early detection of high-risk squamous cell carcinoma and the development of novel therapeutic strategies. OBJECTIVE: This study aimed to investigate the expression patterns of silent mating type Information Regulation 2 homolog 6 (SIRT6) in CSCC and its clinical significance. METHODS: The protein expression level of SIRT6 in tissues was detected by immunohistochemistry, and the correlation between SIRT6 expression and clinicopathological parameters in CSCC patients was analyzed. The relative expression of SIRT6 in CSCC cell lineage and tissue specimens was determined by western blotting and PCR. The effect of SIRT6 silencing on cell proliferation was evaluated using cell counting kit 8. Wound healing, transwell method, and flow cytometry were used to investigate the migration, invasion, and cell cycle distribution/apoptosis of CSCC cells after SIRT6 silencing, respectively. Western blot was used to detect the expression of EMT (Epithelial-Mesenchymal Transition), cycle, apoptosis, and other related proteins. RESULTS: The high expression of SIRT6 was correlated with the location of cancer tissue and Broder staging in CSCC patients. Knockdown of SIRT6 inhibited the proliferation, migration, invasion and EMT of CSCC cells, and promoted their apoptosis, with cells blocked in G1 phase. STUDY LIMITATIONS: No animal experiments were conducted to further verify the results. CONCLUSION: Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.

RGA1 regulates grain size, rice quality and seed germination in the small and round grain mutant srg5.

BACKGROUND: Generating elite rice varieties with high yield and superior quality is the main goal of rice breeding programs. Key agronomic traits, including grain size and seed germination characteristics, affect the final yield and quality of rice. The RGA1 gene, which encodes the α-subunit of rice G-protein, plays an important role in regulating rice architecture, seed size and abiotic stress responses. However, whether RGA1 is involved in the regulation of rice quality and seed germination traits is still unclear. RESULTS: In this study, a rice mutant small and round grain 5 (srg5), was identified in an EMS-induced rice mutant library. Systematic analysis of its major agronomic traits revealed that the srg5 mutant exhibited a semi-dwarf plant height with small and round grain and reduced panicle length. Analysis of the physicochemical properties of rice showed that the difference in rice eating and cooking quality (ECQ) between the srg5 mutant and its wild-type control was small, but the appearance quality was significantly improved. Interestingly, a significant suppression of rice seed germination and shoot growth was observed in the srg5 mutant, which was mainly related to the regulation of ABA metabolism. RGA1 was identified as the candidate gene for the srg5 mutant by BSA analysis. A SNP at the splice site of the first intron disrupted the normal splicing of the RGA1 transcript precursor, resulting in a premature stop codon. Additional linkage analysis confirmed that the target gene causing the srg5 mutant phenotype was RGA1. Finally, the introduction of the RGA1 mutant allele into two indica rice varieties also resulted in small and round rice grains with less chalkiness. CONCLUSIONS: These results indicate that RGA1 is not only involved in the control of rice architecture and grain size, but also in the regulation of rice quality and seed germination. This study sheds new light on the biological functions of RGA1, thereby providing valuable information for future systematic analysis of the G-protein pathway and its potential application in rice breeding programs.

Elucidation of the dominant factors influencing N2O emission in water-level fluctuation zones in a karst canyon reservoir, southwest China.

The water-level fluctuations zones (WLFZs) are crucial transitional interfaces within river-reservoir systems, serving as hotspots for N2O emission. However, the comprehension of response patterns and mechanisms governing N2O emission under hydrological fluctuation remains limited, especially in karstic canyon reservoirs, which introduces significant uncertainty to N2O flux assessments. Soil samples were collected from the WLFZs of the Hongjiadu (HJD) Reservoir along the water flow direction from transition zone (T1 and T2) to lacustrine zone (T3, T4 and T5) at three elevations for each site. These soil columns were used to conduct simulation experiments under various water-filled pore space gradients (WFPSs) to investigate the potential N2O flux pattern and elucidate the underlying mechanism. Our results showed that nutrient distribution and N2O flux pattern differed significantly between two zones, with the highest N2O fluxes in the transition zone sites and lacustrine zone sites were found at 75 % and 95 % WFPS, respectively. Soil nutrient loss in lower elevation areas is influenced by prolonged impoundment durations. The higher N2O fluxes in the lacustrine zone can be attributed to increased nutrient levels resulting from anthropogenic activities. Furthermore, correlation analysis revealed that soil bulk density significantly impacted N2O fluxes across all sites, while NO3-and SOC facilitated N2O emissions in T1-T2 and T4-T5, respectively. It was evident that N2O production primarily contributed to nitrification in the transition zone and was constrained by the mineralization process, whereas denitrification dominated in the lacustrine zone. Notably, the annual N2O efflux from WLFZs accounted for 27 % of that from the water-air interface in HJD Reservoir, indicating a considerably lower contribution than anticipated. Nevertheless, this study highlights the significance of WLFZs as a vital potential source of N2O emission, particularly under the influence of anthropogenic activities and high WFPS gradient.

Structured Catalysts and Catalytic Processes: Transport and Reaction Perspectives.

The structure of catalysts determines the performance of catalytic processes. Intrinsically, the electronic and geometric structures influence the interaction between active species and the surface of the catalyst, which subsequently regulates the adsorption, reaction, and desorption behaviors. In recent decades, the development of catalysts with complex structures, including bulk, interfacial, encapsulated, and atomically dispersed structures, can potentially affect the electronic and geometric structures of catalysts and lead to further control of the transport and reaction of molecules. This review describes comprehensive understandings on the influence of electronic and geometric properties and complex catalyst structures on the performance of relevant heterogeneous catalytic processes, especially for the transport and reaction over structured catalysts for the conversions of light alkanes and small molecules. The recent research progress of the electronic and geometric properties over the active sites, specifically for theoretical descriptors developed in the recent decades, is discussed at the atomic level. The designs and properties of catalysts with specific structures are summarized. The transport phenomena and reactions over structured catalysts for the conversions of light alkanes and small molecules are analyzed. At the end of this review, we present our perspectives on the challenges for the further development of structured catalysts and heterogeneous catalytic processes.

Gastrointestinal trichobezoars in the pediatric population: a retrospective study.

BACKGROUND: Trichobezoar is an extremely rare condition characterized by a foreign body in the gastrointestinal tract (GIT) among children. The foreign body may exist in the digestive tract for several years, and it becomes evident if complications develop. The current study aimed to present 21 cases of GIT trichobezoars. METHODS: Retrospective analysis of children who were diagnosed with trichobezoars between August 2012 and December 2022. Patient demographics, clinical presentation, diagnosis, and therapy were collected and analyzed.Twenty-one patients had GIT trichobezoars. Data were collected and analyzed retrospectively. RESULTS: Twenty-one patients were identified. All patients were female. Their mean age at admission was 8.9 ± 1.9 years. Furthermore, 19 (90.5%) patients presented with abdominal pain, 16 (76.2%) with vomiting, and 13 (61.9%) with a palpable mass. Sixteen patients underwent gastroduodenoscopy. Among them, 15 had gastric trichobezoars. Moreover, 12 patients underwent computed tomography scan. Eight patients presented with gastric and small intestinal BZs, one presented with increased small intestinal contents with dilation, and one presented with abundant gastric contents. Then, 20 patients underwent surgery. Among them, five underwent laparoscopic-assisted minilaparotomy (LAML), and the rest underwent laparotomy. The results showed that 10 (50%) patients had gastric trichobezoars; 7 (35%), Rapunzel syndrome; and 3 (15%), small bowel trichobezoars. Two patients developed superficial wound infection postoperatively. One patient had a recurrent gastric trichobezoar. CONCLUSION: Trichobezoar should be considered in young girls with a history of hair eating or those with hair in the vomit or feces. Timely diagnosis and aggressive treatment are the keys to reducing complications and improving prognosis. Laparoscopic-assisted minilaparotomy is a safe, feasible, and effective surgical method for treating trichobezoars.

Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Neutrophil activation and clonal CAR-T re-expansion underpinning cytokine release syndrome during ciltacabtagene autoleucel therapy in multiple myeloma.

Cytokine release syndrome (CRS) is the most common complication of chimeric antigen receptor redirected T cells (CAR-T) therapy. CAR-T toxicity management has been greatly improved, but CRS remains a prime safety concern. Here we follow serum cytokine levels and circulating immune cell transcriptomes longitudinally in 26 relapsed/refractory multiple myeloma patients receiving the CAR-T product, ciltacabtagene autoleucel, to understand the immunological kinetics of CRS. We find that although T lymphocytes and monocytes/macrophages are the major overall cytokine source in manifest CRS, neutrophil activation peaks earlier, before the onset of severe symptoms. Intracellularly, signaling activation dominated by JAK/STAT pathway occurred prior to cytokine cascade and displayed regular kinetic changes. CRS severity is accurately described and potentially predicted by temporal cytokine secretion signatures. Notably, CAR-T re-expansion is found in three patients, including a fatal case characterized by somatic TET2-mutation, clonal expanded cytotoxic CAR-T, broadened cytokine profiles and irreversible hepatic toxicity. Together, our findings show that a latent phase with distinct immunological changes precedes manifest CRS, providing an optimal window and potential targets for CRS therapeutic intervention and that CAR-T re-expansion warrants close clinical attention and laboratory investigation to mitigate the lethal risk.

Alkaline-earth ion stabilized sub-nano-platinum tin clusters for propane dehydrogenation.

The strong promotion effects of alkali/alkaline earth metals are frequently reported for heterogeneous catalytic processes such as propane dehydrogenation (PDH), but their functioning principles remain elusive. This paper describes the effect of the addition of calcium (Ca) on reducing the deactivation rate of platinum-tin (Pt-Sn) catalyzed PDH from 0.04 h-1 to 0.0098 h-1 at 873 K under a WHSV of 16.5 h-1 of propane. The Pt-Sn-Ca catalyst shows a high propylene selectivity of >96% with a propylene production rate of 41 molC3H6 (gPt h)-1 and ∼1% activity loss after regeneration. The combination of characterization and DFT simulations reveals that Ca acts as a structural promoter favoring the transition of Snn+ in the parent catalyst to Sn0 during reduction, and the latter is an electron donor that increases the electron density of Pt. This greatly suppresses coke formation from deep dehydrogenation. Moreover, it was found that Ca promotes the formation of a highly reactive and sintering-resistant sub-nano Pt-Sn alloy with a diameter of approximately 0.8 nm. These lead to high activity and selectivity for the Pt-Sn-Ca catalyst for PDH.

Metastable gallium hydride mediates propane dehydrogenation on H2 co-feeding.

In heterogeneous catalysis, the catalytic dehydrogenation reactions of hydrocarbons often exhibit a negative pressure dependence on hydrogen due to the competitive chemisorption of hydrocarbons and hydrogen. However, some catalysts show a positive pressure dependence for propane dehydrogenation, an important reaction for propylene production. Here we show that the positive activity dependence on H2 partial pressure of gallium oxide-based catalysts arises from metastable hydride mediation. Through in situ spectroscopic, kinetic and computational analyses, we demonstrate that under reaction conditions with H2 co-feeding, the dissociative adsorption of H2 on a partially reduced gallium oxide surface produces H atoms chemically bonded to coordinatively unsaturated Ga atoms. These metastable gallium hydride species promote C-H bond activation while inhibiting deep dehydrogenation. We found that the surface coverage of gallium hydride determines the catalytic performance. Accordingly, benefiting from proper H2 co-feeding, the alumina-supported, trace additive-modified gallium oxide catalyst GaOx-Ir-K/Al2O3 exhibited high activity and selectivity at high propane concentrations.