Search

Our understanding of climate dynamics during millennial-scale events is incomplete, partially due to the lack of their precise phase analyses under various boundary conditions. Here we present nine speleothem oxygen-isotope records from mid-to-low-latitude monsoon regimes with sub-centennial age precision and multi-annual resolution, spanning the Heinrich Stadial 2 (HS2) - a millennial-scale event that occurred at the Last Glacial Maximum. Our data suggests that the Greenland and Antarctic ice-core chronologies require +320- and +400-year adjustments, respectively, supported by extant volcanic evidence and radiocarbon ages. Our chronological framework shows a synchronous HS2 onset globally. Our records precisely characterize a centennial-scale abrupt "tropical atmospheric seesaw" superimposed on the conventional "bipolar seesaw" at the beginning of HS2, implying a unique response/feedback from low-latitude hydroclimate. Together with our observation of an early South American monsoon shift at the HS2 termination, we suggest a more active role of low-latitude hydroclimate dynamics underlying millennial events than previously thought.

Background and purpose: Chimeric antigen receptor T (CAR-T) cell technology has been widely used in the field of blood tumor treatment. Lentivirus transduction is a key link in the preparation of CAR-T cells, which is closely related to the quality of CAR-T cells. Therefore, the parameters involved in the lentivirus transduction process still need to be further optimized. This study aimed to investigate the effects of multiplicity of infection (MOI), incubation density, activation time before transduction and transduction system height on anti-CD30 CAR-T cells in lentiviral transduction T cells carrying CD30 antibody sequences, optimize the transduction conditions of CAR-T cells, and improve transduction efficiency and CAR-T cells function. Methods: Different MOI, incubation density, activation time before transduction and transduction system height were used to optimize the transduction of human peripheral blood-derived T cells, then proliferation capacity, transduction efficiency, cell viability and killing efficiency in vitro of anti-CD30 CAR-T cells were detected. Results: When the MOI was 1.00, 1.50 and 3.00, the transduction efficiency and effective cell number were significantly higher than those in the 0.00, 0.25 and 0.50 groups. When the incubation density was greater than 0.5×107 cells/mL, the incubation density had no significant effect on the transduction efficiency of T cells. The cell viability rate of the 72 h group was lower than 80%, which was lower compared with other groups significantly, the transduction efficiency of 24 and 48 h was significantly higher compared with the 0 h, 8 h and 16 h groups, and the expansion rate of CAR-T cells in the 48 h group was significantly higher compared with the 24 h group. The transduction efficiency and proliferation capacity of 0.16 mm in height of transduction system were significantly higher compared with the 0.53 mm group, however, had no significant effect on killing efficiency of CAR-T cells in vitro. Conclusion: Through the comprehensive evaluation of CAR-T cells function, the optimal transduction conditions for lentivirus include MOI of 1.00, incubation density of 1.0×107 cells/mL, activation before transduction for 48 h and transduction system height of 0.16 mm.

Objective SLE is a common multisystem autoimmune disease with chronic inflammation. Many efficacy evaluation indicators of randomised clinical trials (RCTs) for SLE have been proposed but the comparability remains unknown. We aim to explore the preference and comparability of indicators reporting response rate and provide basis for primary outcome selection when evaluating the efficacy of SLE pharmaceutical treatment.Methods We systematically searched three databases and three registries to identify pharmacological intervention-controlled SLE RCTs. Relative discriminations between indicators were assessed by the Bayesian hierarchical linear mixed model.Results 33 RCTs met our inclusion criteria and we compared eight of the most commonly used indicators reporting response rate. SLE Disease Activity Index 4 (SLEDAI-4) and SLE Responder Index 4 were considered the best recommended indicators reporting response rate to discriminate the pharmacological efficacy. Indicator preference was altered by disease severity, classification of drugs and outcome of trials, but SLEDAI-4 had robust efficacy in discriminating ability for most interventions. Of note, BILAG Index-based Combined Lupus Assessment showed efficacy in trials covering all-severity patients, as well as non-biologics RCTs. The British Isles Lupus Assessment Group response and Physician’s Global Assessment response were more cautious in evaluating disease changes. Serious adverse event was often applied to evaluate the safety and tolerability of treatments rather than efficacy.Conclusions The impressionable efficacy discrimination ability of indicators highlights the importance of flexibility and comprehensiveness when choosing primary outcome(s). As for trials that are only evaluated by SLEDAI-4, attention should be paid to outcome interpretation to avoid the exaggeration of treatment efficacy. Further subgroup analyses are limited by the number of included RCTs.PROSPERO registration number CRD42022334517.