Multiplex Asymmetric PCR by Combining the Amplification Refractory Mutation System with the Homo-Tag-Assisted Nondimer System.

Asymmetric PCR is widely used to produce single-stranded amplicons (ss-amplicons) for various downstream applications. However, conventional asymmetric PCR schemes are susceptible to events that affect primer availability, which can be exacerbated by multiplex amplification. In this study, a new multiplex asymmetric PCR approach that combines the amplification refractory mutation system (ARMS) with the homo-Tag-assisted nondimer system (HANDS) is described. ARMS-HANDS (A-H) PCR utilizes equimolar-tailed forward and reverse primers and an excess Tag primer. The tailed primer pairs initiate exponential symmetric amplification, whereas the Tag primer drives linear asymmetric amplification along fully matched strands but not one-nucleotide mismatched strands, thereby generating excess ss-amplicons. The production of ss-amplicons is validated using agarose gel electrophoresis, sequencing, and melting curve analysis. Primer dimer alleviation is confirmed by both the reduced Loss function value and a 20-fold higher sensitivity in an 11-plex A-H PCR assay than in an 11-plex conventional asymmetric PCR assay. Moreover, A-H PCR demonstrates unbiased amplification by its allele quantitative ability in correct identification of all 31 trisomy 21 samples among 342 clinical samples. A-H PCR is a new generation of multiplex asymmetric amplification approach with various applications, especially when sensitive and quantitative detection is required.

Carbon pools in forest systems and new estimation based on an investigation of carbon sequestration.

Forests, the ancient wooden giants, are both symbols of natural beauty and reservoirs of carbon stocks. The current climate crisis has created an urgent need for an in-depth study of forest ecosystems and carbon stocks. Based on forest inventory data from field surveys and four bioclimatic zones [Zone 1 (Z1, humid forest), Zone 2 (Z2, semi-humid forest), Zone 3 (Z3, semi-humid to semi-arid forest-grassland), and Zone 4 (Z4, semi-arid typical grassland)], two methods [Method 1 (M1) and Method 2 (M2)] were used to estimate carbon stocks in forest ecosystems in Shaanxi Province, China, and explored the spatial patterns of carbon pools and potential influences. The total forest ecosystem carbon pool amounted to 520.80 Tg C, of which 53.60% was stored aboveground, 17.16% belowground, and 29.24% in soil (depth of 0-10 cm). Spatially, there were marked north-south gradients in both biomass (Z2 > Z3 > Z1 > Z4) and soil organic carbon densities (Z1 > Z2 > Z3 > Z4). The differences between aboveground and belowground biomass carbon density across broadleaf, needle-leaf, and broadleaf and needle-leaf mixed forest were not pronounced, while soil organic carbon density had the order of broadleaf (18.38 Mg C/ha) > needle-leaf (11.29 Mg C/ha) > broadleaf and needle-leaf mixed forest (10.33 Mg C/ha). Under an ideal scenario that excludes external factors, mainly forest growth, the sequestration potential of forest biomass by 2032 was estimated by M1 as 85.43 Tg, and by M2 to be substantially higher at 176.21 Tg. As of 2062, M1 estimated 155.97 Tg of sequestration potential for forest biomass. The spatial patterns of forest biomass and soil carbon density were closely related to climatic factors, and these relationships allowed the spatial division into two distinct climatic regions. Moreover, biomass carbon density was significantly correlated with the normalized difference vegetation index, soil silt, and elevation. This study provides key information for promoting the strategic shift from light-green to deep-green forest systems in Shannxi Province and updates the estimation methods of forest ecosystems' carbon pools based on field surveys.

Cartilage protective and anti-edema effects of JTF in osteoarthritis via inhibiting NCOA4-HMGB1-driven ferroptosis and aquaporin dysregulation.

BACKGROUND: Preventing joint edema is crucial in halting osteoarthritis (OA) progression. Growing clinical evidence indicate that Jianpi-Tongluo Formula (JTF) may have a promising anti-edema effect. However, the therapeutic properties of JTF and the underlying mechanisms remains unclear. MATERIALS AND METHODS: An OA rat model was established and employed to evaluate pharmacological effects of JTF in vivo based on dynamic histopathologic assessments and micro-CT observations. Then, OA-related genes and potential targets of JTF were identified through clinical transcriptomic data analysis and "disease gene-drug target" network analysis, which were verified by a series of in vivo experiments. RESULTS: JTF administration effectively reduced pain and joint edema, inhibited matrix degradation, chondrocyte apoptosis, and aquaporin expression in OA rats. Notably, JTF dose-dependently reversed damage-associated molecular patterns and inflammatory factor upregulation. Mechanically, our "disease gene-drug target" network analysis indicated that the NCOA4-HMGB1-GSK3B-AQPs axis, implicated in ferroptosis and aquaporin dysregulation, may be potentially served as a target of JTF against OA. Accordingly, JTF mitigated NCOA4, HMGB1, and GSK3B expression, oxidative stress, and iron metabolism aberrations in OA rats. Furthermore, JTF treatment significantly attenuated the aberrant upregulation of AQP1, AQP3, and AQP4 proteins observed in cartilage tissues of OA rats. CONCLUSION: Our data reveal for the first time that JTF may exert cartilage protective and anti-edema effects in osteoarthritis therapy by inhibiting NCOA4-HMGB1-driven ferroptosis and aquaporin dysregulation.

Acupressure: a possible therapeutic strategy for anxiety related to COVID-19: a meta-analysis of randomized controlled trials.

Background: From the end of 2019 to December 2023, the world grappled with the COVID-19 pandemic. The scope and ultimate repercussions of the pandemic on global health and well-being remained uncertain, ushering in a wave of fear, anxiety, and worry. This resulted in many individuals succumbing to fear and despair. Acupoint massage emerged as a safe and effective alternative therapy for anxiety relief. However, its efficacy was yet to be extensively backed by evidence-based medicine. This study aimed to enhance the clinical effectiveness of acupoint massage and extend its benefits to a wider population. It undertakes a systematic review of the existing randomized controlled trials (RCTs) assessing the impact of acupoint massage on anxiety treatment, discussing its potential benefits and implications. This research aims to furnish robust evidence supporting anxiety treatment strategies for patients afflicted with COVID-19 disease and spark new approaches to anxiety management. Objectives: This study evaluates the evidence derived from randomised controlled trials (RCTs), quantifies the impact of acupressure on anxiety manifestations within the general population, and proposes viable supplementary intervention strategies for managing COVID-19 related anxiety. Materials and methods: This review included RCTs published between February 2014 and July 2023, that compared the effects of acupressure with sham control in alleviating anxiety symptomatology as the outcome measure. The studies were sourced from the multiple databases, including CINAHL, EBM Reviews, Embase, Medline, PsycINFO, Scopus and Web of Science. A meta-analysis was performed on the eligible studies, and an overall effect size was computed specifically for the anxiety outcome. The Cochrane Collaboration Bias Risk Assessment Tool (RevMan V5.4) was employed to assess bias risk, data integration, meta-analysis, and subgroup analysis. The mean difference, standard mean deviation, and binary data were used to represent continuous outcomes. Results: Of 1,110 studies of potential relevance, 39 met the criteria for inclusion in the meta-analysis. The majority of the studies reported a positive effect of acupressure in assuaging anticipatory anxiety about treatment. Eighteen studies were evaluated using the STAI scale. The acupressure procedures were thoroughly documented, and studies exhibited a low risk of bias. The cumulative results of the 18 trials showcased a more substantial reduction in anxiety in the acupressure group compared to controls (SMD = -5.39, 95% CI -5.61 to -5.17, p < 0.01). A subsequent subgroup analysis, based on different interventions in the control group, demonstrated improvement in anxiety levels with sham acupressure in improving changes in anxiety levels (SMD -1.61, 95% CI: -2.34 to -0.87, p < 0.0001), and blank controls (SMD -0.92, 95% CI: -2.37 to 0.53, p = 0.22). Conclusion: In the clinical research of traditional Chinese medicine treatment of anxiety, acupressure demonstrated effectiveness in providing instant relief from anxiety related to multiple diseases with a medium effect size. Considering the increasing incidence of anxiety caused by long COVID, the widespread application of acupressure appears feasible. However, the results were inconsistent regarding improvements on physiological indicators, calling for more stringent reporting procedures, including allocation concealment, to solidify the findings.

Comparative assessment of leaf photosynthetic capacity datasets for estimating terrestrial gross primary productivity.

The maximum Rubisco carboxylation rate normalized to 25 °C (Vcmax25) is a key parameter in terrestrial biosphere models for simulating carbon cycling. Recently, global distributions of Vcmax25 have been derived through various methods and different data, including field measurements, ecological optimality theory (EOT), leaf chlorophyll content (LCC), and solar-induced chlorophyll fluorescence (SIF). However, direct validation poses challenges due to high uncertainty arising from limited ground-based observations. This study conducted an indirect evaluation of four Vcmax25 datasets by assessing the accuracy of gross primary productivity (GPP) simulated using the Biosphere-atmosphere Exchange Process Simulator (BEPS) at both site and global scales. Results indicate that, compared to utilizing Vcmax25 fixed by plant functional types (PFT) derived from field measurements, incorporating Vcmax25 derived from SIF and LCC (SIF + LCC), or solely LCC, into BEPS significantly reduces simulated errors in the annual total GPP, with a 23.2 %-25.1 % decrease in the average absolute bias across 196 FLUXNET2015 sites. Daily GPP for evergreen needleleaf forests, deciduous broadleaf forests, shrublands, grasslands, and croplands shows a 7.8 %-27.6 % decrease in absolute bias, primarily attributed to reduced simulation errors during off-peak seasons of vegetation growth. Conversely, the annual total GPP error simulated using EOT-derived Vcmax25 increases slightly (2.2 %) compared to that simulated using PFT-fixed Vcmax25. This is primarily due to a significant overestimation in evergreen broadleaf forests and underestimation in croplands, despite slight increased accuracy for other PFTs. The global annual GPP simulated using Vcmax25 with seasonal variations (i.e., LCC Vcmax25 and SIF + LCC Vcmax25) yields a 4.3 %-7.3 % decrease compared to that simulated using PFT-fixed Vcmax25. Compared to FLUXCOM and GOSIF GPP products, the GPP simulated based on SIF + LCC Vcmax25 and LCC Vcmax25 demonstrates better consistency (R2 = 0.91-0.93, RMSE = 314.2-376.6 g C m-2 yr-1). This study underscores the importance of accurately characterizing the spatiotemporal variations in Vcmax25 for the accurate simulation of global vegetation productivity.

Electroacupuncture Enhances the Functional Connectivity of Limbic System to Neocortex in the 5xFAD Mouse Model of Alzheimer's Disease.

Our previous study revealed that acupuncture may exhibit therapeutic effects on Alzheimer's disease (AD) through the activation of metabolism in memory-related brain regions. However, the underlying functional mechanism remains poorly understood and warrants further investigation. In this study, we used resting-state functional magnetic resonance imaging (rsfMRI) to explore the potential effect of electroacupuncture (EA) on the 5xFAD mouse model of AD. We found that the EA group exhibited significant improvements in the number of platforms crossed and the time spent in the target quadrant when compared with the Model group (p < 0.05). The functional connectivity (FC) of left hippocampus (Hip) was enhanced significantly among 12 regions of interest (ROIs) in the EA group (p < 0.05). Based on the left Hip as the seed point, the rsfMRI analysis of the entire brain revealed increased FC between the limbic system and the neocortex in the 5xFAD mice after EA treatment. Additionally, the expression of amyloid-ß(Aß) protein and deposition in the Hip showed a downward trend in the EA group compared to the Model group (p < 0.05). In conclusion, our findings indicate that EA treatment can improve the learning and memory abilities and inhibit the expression of Aß protein and deposition of 5xFAD mice. This improvement may be attributed to the enhancement of the resting-state functional activity and connectivity within the limbic-neocortical neural circuit, which are crucial for cognition, motor function, as well as spatial learning and memory abilities in AD mice.

Preemptive inotuzumab ozogamicin eradicated measurable residual disease in Ph-negative acute lymphoblastic leukemia relapsed post CD19 CART therapy.

There are no reports of application of inotuzumab ozogamicin (InO) for the treatment of MRD in r/r B-ALL. We firstly report the efficacy of InO for a patient experienced morphological relapse after HSCT and molecular relapse after CART therapy.

Cucurbitacin B protects against myocardial ischemia-reperfusion injury through activating JAK2/STAT3 signaling pathway.

Cucurbitacin B, a tetracyclic triterpenoid compound extracted from various plants, has been proven to exert a vital role in various diseases. However, the effect of cucurbitacin B on myocardial infarction (MI) and ischemia-reperfusion (I/R) injury is still relatively unclear. The main purpose of the present study was to investigate the effect of cucurbitacin B on cell apoptosis and oxidative damage after myocardial I/R injury in vitro and in vivo and elucidate the molecular mechanisms underlying its role. The 56-day-old adult mice and 1-day-old neonatal mice cardiomyocytes were used to construct I/R or oxygen-glucose deprivation/reoxygenation (OGD/R) injury models. The oxidative injury, western blot and TUNEL assay were performed to evaluate cardiomyocyte damage in the present study. In vitro， we confirmed that cucurbitacin B could attenuate LDH release, oxidative stress and cell apoptosis in cardiomyocytes exposed to OGD/R. Besides, we confirmed in an adult I/R mouse model that cucurbitacin B can improve cardiac repair and block cell apoptosis in the acute phase (24 h) post-myocardial I/R injury, as well as promote long-term cardiac function and fiber scar area after 28 days of I/R. Mechanically, we clarify that cucurbitacin B exerts cardiomyocyte protective effects through activating the JAK2/STAT3 signaling pathway. In conclusion, our study elucidates for the first time the protective role of cucurbitacin B in cardiac I/R injury, which provides a novel perspective for better prevention of I/R injury through the JAK2/STAT3 signaling pathway.

Combination of computed tomography measurements and flexible video bronchoscope guidance for accurate placement of the right-sided double-lumen tube: a randomised controlled trial.

OBJECTIVE: To compare the modified strategy for the right-sided double-lumen tube (R-DLT) placement using a combination of CT measurements and flexible video bronchoscopy guidance with traditional bronchoscopy technique. TRIAL DESIGN, SETTING AND PARTICIPANTS: Double-blind, parallel randomised control trial at a tertiary care medical centre in China. 100 patients undergoing video-assisted thoracoscopic surgery and requiring R-DLT were randomly allocated to the control group and the intervention group. INTERVENTION: The control group used the traditional bronchoscopy-guided technique. In the intervention group, the length and anteroposterior diameter of the right main bronchus (RMB) were measured on CT images to select the side and size of the Rüsch tube, and then a black depth marker was placed on the tube according to the difference between the length of the RMB and the bronchial cuff. Under the guidance of bronchoscopy, the depth marker should be placed parallel to the tracheal carina and a characteristic white line on the tube should be parallel to the midline of the tracheal carina. MAIN OUTCOMES: The primary endpoint was the positioning of right upper lobe (RUL) ventilatory slot and RUL bronchial orifice. The secondary endpoints included intubation data and perioperative adverse events. RESULTS: Compared with the control group, our modified strategy significantly increased the optimal and acceptable position rate (76% vs 98%, respectively; p<0.039), decreased the replacement rate (80% vs 94%; p=0.042), shortened the intubation time (101.4±7.3 s vs 75.2±8.1 s; p=0.019) and reduced the incidence of transient hypoxaemia (25% vs 6%; p=0.022), subglottic resistance (20% vs 6%; p=0.037), tracheobronchial injury (35% vs 13%; p=0.037) and postoperative RUL collapse (15% vs 2%; p=0.059). CONCLUSION: This study demonstrates the superiority of our strategy and provides a new viable method for R-DLT placement. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1900021676).

China's current forest age structure will lead to weakened carbon sinks in the near future.

Forests are chiefly responsible for the terrestrial carbon sink that greatly reduces the buildup of CO2 concentrations in the atmosphere and alleviates climate change. Current predictions of terrestrial carbon sinks in the future have so far ignored the variation of forest carbon uptake with forest age. Here, we predict the role of China's current forest age in future carbon sink capacity by generating a high-resolution (30 m) forest age map in 2019 over China's landmass using satellite and forest inventory data and deriving forest growth curves using measurements of forest biomass and age in 3,121 plots. As China's forests currently have large proportions of young and middle-age stands, we project that China's forests will maintain high growth rates for about 15 years. However, as the forests grow older, their net primary productivity will decline by 5.0% ± 1.4% in 2050, 8.4% ± 1.6% in 2060, and 16.6% ± 2.8% in 2100, indicating weakened carbon sinks in the near future. The weakening of forest carbon sinks can be potentially mitigated by optimizing forest age structure through selective logging and implementing new or improved afforestation. This finding is important not only for the global carbon cycle and climate projections but also for developing forest management strategies to enhance land sinks by alleviating the age effect.

Combination of venetoclax with BCR-ABL tyrosine kinase inhibitor as a therapeutic strategy for Philadelphia chromosome-positive leukemias.

OBJECTIVES: Venetoclax has shown synergism with BCR-ABL1 tyrosine kinase inhibitors (TKIs) in preclinical studies for patients with Philadelphia chromosome-positive (Ph+) leukemias. This combination may suggest a novel treatment strategy for Ph + leukemias. METHODS: We conducted a retrospective study to summarize the activity of combining venetoclax and BCR-ABL1 TKI-based therapies in Ph + leukemias. RESULT: A total of 18 patients with Ph + leukemias were enrolled in this study. At the time of venetoclax and TKI-based therapy, 5 patients were initially diagnosed, with Ph + acute myeloid leukemia (AML) (n = 1) and mixed phenotype acute leukemia (MPAL) (n = 4), 7 patients had chronic myeloid leukemia at blastic phase (CML-BP), and the remaining 6 patients had relapsed or refractory to prior therapy. The overall response rate (ORR) was 88.9% (9 CR, 2 CRi, 4 MLFS, 1 PR), and a major molecular response (MMR) (or better) was achieved in 7 (38.8%) of all patients. With a median follow-up of 7.0 months (range, 2.3-15.6), 15 (83.3%) were in continuous CR at the time of this analysis, with a 1-year OS of 85.6%, 1-year LFS of 76.7%, and 1-year CIR of 22.4%. Moreover, 10 of 18 patients were treated with venetoclax, TKI and hypomethylating agent (HMA) regimens, which also associated with a high ORR rate (6 CR, 1 CRi, 3 MLFS), and can be used for induction or salvage therapy. CONCLUSION: Venetoclax and TKI-based combination regimens may be a feasible approach for Ph + leukemias, and prospective studies are needed to properly assess the safety, tolerability and efficacy of this regimen.

Effects of (20 R)-Panaxadiol on NAFLD using non­targeted metabolomics in stool.

Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome characterized by hepatocyte steatosis and adipose accumulation with the main lesion in the hepatic lobule, but without a history of excessive alcohol consumption. NAFLD ranges from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), and may further accumulate fibrosis leading to cirrhosis. Many studies have found that ginseng can treat NAFLD. (20 R)-Panaxadiol (PD) is a panax ginseng diol type compound, has been proved that can treat the obesity. This study wants to investigate the effect of PD on non-alcoholic liver disease. We used 20 ob/ob mice and 10 C57BL/6 J mice. C57BL/6 J mice as CONTROL group, ob/ob mice were divided into model group and PD group. In PD group, ob/ob mice were treated with PD for eight weeks(10 mg/kg, the CON and OB group was given the same amount of sodium carboxymethyl cellulose), detected the weight, food intake and serum index, observed the HE staining of liver and intestine, performed the 16 S rRNA and untargeted metabolomics analysis used mice feces, and verify the results by detect the expression of TNF-α, MDA and SOD. In vivo results, PD can improve abnormal glucose and lipid metabolism and liver function. In 16 S rRNA result, we found beneficial bacteria Muribaculaceae and Lactobacillus increased; in untargeted metabolomics analysis, inflammatory metabolites prostaglandin (PG) and lipopolysaccharide (LPS) decreased, antioxidant metabolites FAD and lipoic acid increased. Then, we proceeded the association analysis of gut microbiota and metabolites, the result showed gut microbiota have strongly associated with anti-inflammatory and antioxidant metabolites. In addition, PD improves intestinal wall integrity. Meanwhile, the expression of TNF-α、MDA and SOD were detected, it was verified that PD has the effect of antioxidant and anti-inflammation. Our study showed that PD, as an active ingredient of ginseng, can play an anti-inflammatory and antioxidant role by improving intestinal metabolites, thereby preventing and treating non-alcoholic fatty liver disease to a certain extent.

Effects of comprehensive landscape patterns on water quality and identification of key metrics thresholds causing its abrupt changes.

Comprehensive landscape patterns influence water quality with multiple factors, complex processes, and scale dependence. However, studies identifying landscape thresholds causing abrupt water quality changes and characterizing the contribution of topography to water quality are still limited. Exploring the impact mechanisms of natural geographical and landscape characteristics on spatial and seasonal water quality variations is conducive to watershed water resource protection and ecosystem restoration. Based on water quality monitoring data of Minjiahe River in the typical headwater area of the upstream Dan River in China from 2019 to 2021, we employed redundancy analysis, partial redundancy analysis, and nonparametric change-point analysis to analyze the relationship between stream water quality and multi-spatial scale comprehensive landscape patterns, to obtain the interactive and independent contributions of different landscape categories at multi-spatial scales on water quality, and to find the key landscape threshold leading to abrupt changes in water quality. Results showed that landscape configuration, landscape composition, and topographic factors collectively explain over 89.1% of water quality variation. Most seasonal variations in water quality were primarily caused by landscape configuration. The landscape composition was mainly responsible for the differences in water quality variations among spatial scales. The topographic factors made the least independent contribution and had a potential impact on overall water quality variation. In order to protect the water quality of streams, it is more reasonable to regulate the landscape at different scales. At the sub-catchment scale, interspersion and juxtaposition index (IJI) and landscape shape index (LSI) should be controlled below 82% and 22. At the 100 m riparian scale, farmland, urban land, IJI, and LSI should be controlled below 29%, 6.5%, 92%, and 26, respectively. Our results provide important guidance for optimizing landscape patterns and water conservation in the watershed.

The Use of SARS-CoV-2-Positive Donors in Hematopoietic Stem Cell Transplantation.

BACKGROUND: Since 2019, the SARS-CoV-2 pandemic has become a global issue due to its high fatality rate. Over time, the characteristics of the virus have evolved and led to the creation of an omicron strain with higher infectivity but a significantly decreased fatality rate. For patients in urgent need of hematopoietic stem cell transplantation (HSCT), whether the SARS-CoV-2 infection status of donors has a significant impact on HSCT recipients should be clarified. METHODS: To estimate the transplantation risk of SARS-CoV-2-positive donors, 24 patients who underwent HSCT from December 1, 2022 to January 30, 2023 were retrospectively included. The ratio of the observation group (SARS-CoV-2-positive donors, n = 12) to the control group (SARS-CoV-2-negative donors, n = 12) was 1:1. We observed the time of hematopoietic reconstruction, donor chimerism, severe infection, acute graft vs host disease, and hepatic vein occlusion disease during hematopoietic reconstruction. RESULTS: In the observation group, the average time of myeloid hematopoietic reconstruction was 11.58 days, and in the control group, it was 12.17 days (P = .3563 [>.05]). On average, all patients achieved a 90% donor chimerism rate of +13.58 (±4.5) days (P = .5121 [>.05]). The average percentage of patients that achieved successful hematopoietic reconstruction was 96.75% in the observation group and 96.31% in the control group (P = .7819 [>.05]). A total of 6 adverse events occurred during this study: 3 in the observation group and 3 in the control group. CONCLUSIONS: Our preliminary results showed favorable short-term outcomes in recipients of SARS-CoV-2-positive HCST donors.

Anti-CD19 CAR T-cell consolidation therapy combined with CD19+ feeding T cells and TKI for Ph+ acute lymphoblastic leukemia.

We conducted a single-arm, open-label, single-center phase 1 study to assess the safety and efficacy of multicycle-sequential anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in combination with autologous CD19+ feeding T cells (FTCs) and tyrosine kinase inhibitor (TKI) as consolidation therapy in patients under the age of 65 years with de novo Ph-positive CD19+ B-cell acute lymphoblastic leukemia. Participants were given induction chemotherapy as well as systemic chemotherapy with TKI. Afterward, they received a single cycle of CD19 CAR T-cell infusion and another 3 cycles of CD19 CAR T-cell and CD19+ FTC infusions, followed by TKI as consolidation therapy. CD19+ FTCs were given at 3 different doses. The phase 1 results of the first 15 patients, including 2 withdrawals, are presented. The most common adverse events were cytopenia (13/13) and hypogammaglobinemia (12/13). There was no incidence of cytokine release syndrome above grade 2 or immune effector cell-associated neurotoxicity syndrome or grade 4 nonhematological toxicities. All 13 patients achieved complete remission, including 12 patients with a complete molecular response (CMR) at the data cutoff. The relapse-free survival was 84%, and the overall survival was 83% with a median follow-up of 27 months. The total number of CD19-expressing cells decreased with an increasing CMR rate. CD19 CAR T cells survived for up to 40 months, whereas CD19+ FTCs vanished in 8 patients 3 months after the last infusion. These findings could form the basis for the development of an allo-HSCT-free consolidation paradigm. This trial was registered at www.clinicaltrials.gov as #NCT03984968.

Croceibacterium selenioxidans sp. nov., isolated from seleniferous soil.

A Gram-negative, aerobic bacterial strain, designated LX-88T, was isolated from seleniferous soil in Enshi, Hubei Province, PR China. Strain LX-88Toxidized elemental selenium to selenite, and produced carotenoids but not bacteriochlorophyll. The isolate grew optimally at 28 °C, pH 8.0 and with 0.5 % (w/v) NaCl. Phylogenetic analysies of the organism's 16S rRNA and bacterial core gene set sequences indicated that LX-88T belongs to the genus Croceibacterium, and has the highest degree of 16S rRNA gene sequence similarity to Croceibacterium soli MN-1T (97.4 %). The LX-88T genome was 3.4 Mbp and had a G+C content of 63.6 mol%. The average nucleotide identity and digital DNA-DNA hybridization values showed low relatedness (below 95 and 70 %, respectively) between strain LX-88T and other strains in the genus Croceibacterium. Ubiquinone-10 was the predominant quinone. The polar lipid profile was dominated by diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, sphingoglycolipid, an unidentified aminolipid, an unidentified phospholipid and an unidentified lipid. The major fatty acid was summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). These physiological and biochemical tests facilitated the differentiation of strain LX-88T from other members of the genus Croceibacterium. The results of this multifaceted taxonomic study indicate that strain LX-88T represents a novel species in the genus Croceibacterium, for which the name Croceibacterium selenioxidans sp. nov. is proposed. The type strain is LX-88T (=MCCC 1K08007T=LMG 32570T).