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To respond to the challenge of global climate change, universities should engage in carbon footprint research to identify effective strategies for mitigating greenhouse gas emissions. In this research, a comprehensive framework tailored for the study of carbon footprints in universities was constructed and used in a university in Northeast China for a case study, based on the GHG Protocol and emission factor methodology. The sources of GHG emissions at this university were identified by the GHG Protocol. Activity data were collected through questionnaire surveys and field visits. The results show that the university’s annual carbon footprint in 2022 stands at 172,473.77 t CO2-eq, with the contributions of Scope 1, 2, and 3 accounting for 2.35%, 64.69%, and 32.96%, respectively. Based on the carbon footprint quantification results, campus carbon reduction strategies were put forward from four perspectives: individual activities, building energy management, energy-loss reduction, and carbon sink, in order to enhance the sustainability of this university. An important difference between this work and previous studies is the explicit emphasis on the necessity of the indicative role of the carbon footprint in carbon reduction efforts. The case demonstrates the application of research framework and methods, providing methodologies and case references for future research on the carbon footprint of universities.

Interferon therapy has been used in clinical practice for more than three decades to treat polycythemia vera (PV) and essential thrombocythemia (ET). However, there has been no systematic investigation of its expected outcomes and potential risks. We performed a systematic review and single-arm meta-analysis to assess the clinical outcomes (hematological response, molecular response, vascular events, hematological transformation, and adverse events) after interferon therapy for patients with PV and ET. A systematic search identified 37 reports, including data from 1794 patients that were published before March 2021. The pooled overall hematological response (OHR) rate was 86%, with better OHR rates observed in studies using long-acting interferon (p < 0.001) and studies with younger patients (p = 0.038). The pooled overall molecular response rate was 48%, and inter-study heterogeneity was also related to patient age (p = 0.009). The overall incidence was 0.42/100 person-years for thrombosis, 0.01/100 person-years for hemorrhage, 0.21/100 person-years for myelofibrotic transformation, and 0.08/100 person-years for leukemic transformation. Compared with hydroxyurea, interferon produced a non-inferior hematological response and a superior molecular response. In conclusion, interferon therapy provided high rates of hematological and molecular response for patients with PV and ET and was associated with a favorable prognosis.

SETD2 , an epigenetic tumor suppressor, is frequently mutated in MLL-rearranged (MLLr) leukemia and relapsed acute leukemia (AL). To clarify the impact of SETD2 mutations on chemotherapy sensitivity in MLLr leukemia, two loss-of-function (LOF) Setd2-mutant alleles ( Setd2 F2478L/WT or Setd2 Ex6-KO/WT ) were generated and introduced, respectively, to the Mll-Af9 knock-in leukemia mouse model. Both alleles cooperated with Mll-Af9 to accelerate leukemia development that resulted in resistance to standard Cytarabine-based chemotherapy. Mechanistically, Setd2-mutant leukemic cells showed downregulated signaling related to cell cycle progression, S, and G2/M checkpoint regulation. Thus, after Cytarabine treatment, Setd2-mutant leukemic cells exit from the S phase and progress to the G2/M phase. Importantly, S and G2/M cell cycle checkpoint inhibition could resensitize the Mll-Af9/Setd2 double-mutant cells to standard chemotherapy by causing DNA replication collapse, mitotic catastrophe, and increased cell death. These findings demonstrate that LOF SETD2 mutations confer chemoresistance on AL to DNA-damaging treatment by S and G2/M checkpoint defects. The combination of S and G2/M checkpoint inhibition with chemotherapy can be explored as a promising therapeutic strategy by exploiting their unique vulnerability and resensitizing chemoresistant AL with SETD2 or SETD2 -like epigenetic mutations.

ASXL1 mutations are frequently found in hematological tumors, and loss of Asxll promotes myeloid transforma- tion in mice. Here we present data supporting a role for an ASXL1-BAP1 complex in the deubiquitylation of mono-ubiquitinylated lysine 119 on Histone H2A （H2AK119ubl） in vivo. The Polycomb group proteins control the expression of the INK4B-ARF-INK4A locus during normal development, in part through catalyzing mono-ubiquit- inylation of H2AK119. Since the activation of the locus INK4B-ARF-INK4A plays a fail-safe mechanism protecting against tumorigenesis, we investigated whether ASXLl-dependent H2A deubiquitylation plays a role in its activation. Interestingly, we found that ASXL1 is specifically required for the increased expression of p15INa4n in response to both oncogenic signaling and extrinsic anti-proliferative signals. Since we found that ASXL1 and BAP1 both are enriched at the INK4B locus, our results suggest that activation of the INK4B locus requires ASXL1/BAPl-mediated deubiqui- tylation of H2AK119ubl. Consistently, our results show that ASXL1 mutations are associated with lower expression levels of p151NK4B and a proliferative advantage of hematopoietic progenitors in primary bone marrow cells, and that depletion of ASXL1 in multiple cell lines results in resistance to growth inhibitory signals. Taken together, this study links ASXLl-mediated H2A deubiquitylation and transcriptional activation of INK4B expression to its tumor sup- pressor functions.

Background: Patients with lower-risk myelodysplastic syndromes (MDS) may experience anemia and a high transfusion burden, alongside a risk of progression to acute myeloid leukemia. Luspatercept, a recombinant fusion protein that acts as an erythroid maturation agent, was FDA/EMA-approved in 2020 based on the phase III MEDALIST trial. There remains an unmet need for anemia treatment in Asian patients for whom red blood cell (RBC) transfusion is a standard of care, and in whom rates/severity of anemia and serum erythropoietin levels are often higher versus Western patients. Objectives: The objective of this study was to assess the efficacy, safety, and tolerability of luspatercept in Asian patients with anemia due to transfusion-dependent lower-risk MDS with ring sideroblasts. Design: This was a phase II, single-arm, interventional bridging study (NCT04477850). Methods: Patients from China and Japan with very low-, low-, or intermediate-risk MDS with ring sideroblasts who were RBC transfusion-dependent received subcutaneous luspatercept starting at 1.0 mg/kg every 3 weeks. The primary endpoint was RBC transfusion independence (TI) ⩾8 weeks (weeks 1–24). Results: There was a statistically significant, clinically meaningful improvement of anemia in Asian patients; 60% (n = 18, p < 0.0001) achieved RBC-TI for ⩾8 weeks and 43% (n = 13) for ⩾12 weeks (weeks 1–24). Safety was consistent with the known profile of luspatercept in MDS. Conclusion: These results support luspatercept as a well-tolerated, efficacious alternative to transfusions for Asian patients with lower-risk MDS, who tend to have more severe anemia. Trial registration: clinicaltrials.gov, NCT04477850.

Moutan Cortex (MC) is a traditional Chinese medicine that contains abundant medicinal components, such as paeonol, paeoniflorin, etc. Paeonol is the main active component of MC. In this study, paeonol was extracted from MC through an ultrasound-assisted extraction process, which is based on single-factor experiments and response surface methodology (RSM). Subsequently, eight macroporous resins of different properties were used to purify paeonol from MC. The main components of the purified extract were identified by ultra-performance liquid chromatography–quadrupole–time of flight–mass spectrometry (UPLC-Q-TOF-MS/MS). The results indicate the optimal parameters are as follows: liquid-to-material ratio 21:1 mL/g, ethanol concentration 62%, ultrasonic time 31 min, ultrasonic temperature 36 °C, ultrasonic power 420 W. Under these extraction conditions, the actual yield of paeonol was 14.01 mg/g. Among the eight tested macroporous resins, HPD-300 macroporous resin was verified to possess the highest adsorption and desorption qualities. The content of paeonol increased from 6.93% (crude extract) to 41.40% (purified extract) after the HPD-300 macroporous resin treatment. A total of five major phenolic compounds and two principal monoterpene glycosides were characterized by comparison with reference compounds. These findings will make a contribution to the isolation and utilization of the active components from MC.

Inflammation has been reported to be related to anemia. As a novel inflammatory marker, Systemic immune-inflammation index (SII) has not been studied with Anemia. The aim of this study was to investigate the possible relationship between SII and anemia. This retrospective cross-sectional survey was conducted using data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES) population. In total, 19851 American adults aged ≥18 years were included. SII was calculated as the platelet count×neutrophil count/lymphocyte count. Anemia was defined as hemoglobin (Hgb) levels of < 13 g/dL in males and < 12 g/dL in females. Logistic regression analyses, subgroup analyses and sensitivity analyses were performed to investigate the relationship between SII and anemia. Our study included a total of 19851 patients, of which 1501 (7.6%) had anemia. After adjusting for all covariates, the multivariate logistic regression analysis showed that a higher SII (In-transform) level was associated with increased likelihood of anemia (OR=1.51, 95% CI: 1.36-1.68, P<0.001). The association between SII and anemia exhibited a nonlinear manner. The positive correlation between SII and anemia was related to the severity of anemia. Subgroup analysis showed that there was no significant dependence on age, family income, body mass index, hypertension, kidney disease and cancer except gender on this positive association. Furthermore, sensitivity analyses confirmed the robustness of our results. Our study demonstrated that SII was positively associated with anemia especially among female participants. And this positive correlation was related to the severity of anemia. Further large-scale prospective studies are still needed to analyze the role of SII in anemia.

Mantle cell lymphoma (MCL) is a phenotypically and genetically heterogeneous malignancy in which the genetic alterations determining clinical indications are not fully understood. Here, we performed a comprehensive whole-exome sequencing analysis of 152 primary samples derived from 134 MCL patients, including longitudinal samples from 16 patients and matched RNA-Seq data from 48 samples. We classified MCL into 4 robust clusters (C1-C4). C1 featured mutated immunoglobulin heavy variable (IGHV), CCND1 mutation, amp(11q13), and active B cell receptor (BCR) signaling. C2 was enriched with del(11q)/ATM mutations and upregulation of NF-κB and DNA repair pathways. C3 was characterized by mutations in SP140, NOTCH1, and NSD2, with downregulation of BCR signaling and MYC targets. C4 harbored del(17p)/TP53 mutations, del(13q), and del(9p), and active MYC pathway and hyperproliferation signatures. Patients in these 4 clusters had distinct outcomes (5-year overall survival [OS] rates for C1-C4 were 100%, 56.7%, 48.7%, and 14.2%, respectively). We also inferred the temporal order of genetic events and studied clonal evolution of 16 patients before treatment and at progression/relapse. Eleven of these samples showed drastic clonal evolution that was associated with inferior survival, while the other samples showed modest or no evolution. Our study thus identifies genetic subsets that clinically define this malignancy and delineates clonal evolution patterns and their impact on clinical outcomes.