A Novel JAK1 Inhibitor SHR0302 Combined With Prednisone for First-Line Treatment of Chronic Graft-Versus-Host Disease: A Phase I Clinical Trial.

Chronic graft-versus-host disease (cGVHD) is a potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation. Standard steroid first-line treatment could not satisfy therapeutic needs due to limited efficacy. As a highly selective Janus kinase (JAK) 1 inhibitor, SHR0302 exhibits a reduced inhibition effect on JAK2 and might have less effect on hematopoiesis. This phase I clinical trial investigated the tolerability and safety of SHR0302 in combination with prednisone, and its early efficacy evidence as a potential first-line treatment to moderate/severe cGVHD. The standard 3 + 3 dose escalation was implemented to find the optimal dose of SHR0302. And prednisone was concurrently administrated with a dose of 1 mg/kg/d and then gradually tapered after 2 weeks. Eighteen patients were enrolled into the study. Grade ≥ 3 treatment-related adverse events were observed in 38.9% of patients. Only one patient developed DLT (grade ≥ 3 hypercholesterolemia) in the highest dose-level group who had pre-existing hypercholesterolemia. The maximum tolerated dose was not reached. No patient discontinued treatment due to AEs. Sixteen out of 18 patients were evaluable for responses, the ORR at week 4 and week 24 were 94.4 and 87.5%, respectively. Overall, the treatment of SHR0302 combined with prednisone was safe and well-tolerated, preliminary clinical results presented a high response for previously untreated cGVHD and a significant reduction in prednisone use in this study. A phase II trial will be conducted to further investigate its therapeutic effects clinically.

Circular mRNA-based TCR-T offers a safe and effective therapeutic strategy for treatment of cytomegalovirus infection.

Circular mRNA (cmRNA) is particular useful due to its high resistance to degradation by exonucleases, resulting in greater stability and protein expression compared to linear mRNA. T cell receptor (TCR)-engineered T cells (TCR-T) represent a promising means of treating viral infections and cancer. This study aimed to evaluate the feasibility and efficacy of cmRNA in antigen-specific-TCR discovery and TCR-T therapy. Using human cytomegalovirus (CMV) pp65 antigen as a model, we found that the expansion of pp65-responsive T cells was induced more effectively by monocyte-derived dendritic cells transfected with pp65-encoding cmRNA compared with linear mRNA. Subsequently, we developed cmRNA-transduced pp65-TCR-T (cm-pp65-TCR-T) that specifically targets the CMV-pp65 epitope. Our results showed that pp65-TCR could be expressed on primary T cells for more than 7 days. Moreover, both in vitro killing and in vivo CDX models demonstrated that cm-pp65-TCR-T cells specifically and persistently kill pp65-and HLA-expressing tumor cells, significantly prolonging the survival of mice. Collectively, our results demonstrated that cmRNA can be used as a more effective technical approach for antigen-specific TCR isolation and identification, and cm-pp65-TCR-T may provide a safe, non-viral, non-integrated therapeutic approach for controlling CMV infection, particularly in patients who have undergone allogeneic hematopoietic stem cell transplantation.

Low-dose anti-thymocyte globulin plus low-dose post-transplant cyclophosphamide-based regimen for prevention of graft-versus-host disease after haploidentical peripheral blood stem cell transplants: a large sample, long-term follow-up retrospective study.

Introduction: The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity for prevention of graft-versus-host disease (GVHD) in haploidentical-peripheral blood stem cell transplantation (haplo-PBSCT), but its impacts on long-term outcomes remain to be defined. Methods: We performed a large sample, long-term follow-up retrospective study to evaluate its efficacy for GVHD prophylaxis. Results: The study enrolled 260 patients, including 162 with myeloid malignancies and 98 with lymphoid malignancies. The median follow-up time was 27.0 months. For the entire cohort, the cumulative incidences (CIs) of grade II-IV and III-IV acute GVHD (aGVHD) by 180 days were 13.46% (95% CI, 9.64%-17.92%) and 5.77% (95% CI, 3.37%-9.07%); while total and moderate/severe chronic GVHD (cGVHD) by 2 years were 30.97% (95% CI, 25.43%-36.66%) and 18.08% (95% CI, 13.68%-22.98%), respectively. The 2-year overall survival (OS), relapse-free survival (RFS), GVHD-free, relapse-free survival (GRFS), non-relapse mortality (NRM), and CIs of relapse were 60.7% (95% CI, 54.8%-67.10%), 58.1% (95% CI, 52.2%-64.5%), 50.6% (95% CI, 44.8-57.1%), 23.04% (95% CI, 18.06%-28.40%), and 18.09% (95% CI, 14.33%-23.97%, respectively. The 1-year CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation were 43.46% (95% CI, 37.39%-49.37%) and 18.08% (95% CI, 13.68%-22.98%), respectively. In multivariate analysis, the disease status at transplantation was associated with inferior survivor outcomes for all patients and myeloid and lymphoid malignancies, while cGVHD had superior outcomes for all patients and myeloid malignancies, but not for lymphoid malignancies. Discussion: The results demonstrated that the novel regimen could effectively prevent the occurrence of aGVHD in haplo-PBSCT.

Metagenomic Next-Generation Sequencing for Pathogens in Bronchoalveolar Lavage Fluid Improves the Survival of Patients with Pulmonary Complications After Allogeneic Hematopoietic Stem Cell Transplantation.

INTRODUCTION: Unbiased metagenomic next-generation sequencing (mNGS) has been used for infection diagnosis. In this study, we explored the clinical diagnosis value of mNGS for pulmonary complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: From August 2019 to June 2021, a prospective study was performed to comparatively analyze the pathogenic results of mNGS and conventional tests for bronchoalveolar lavage fluid (BALF) from 134 cases involving 101 patients with pulmonary complications after allo-HSCT. RESULTS: More pathogens were identified by mNGS than with conventional tests (226 vs 120). For bacteria, the diagnostic sensitivity (P = 0.144) and specificity (P = 0.687) were similar between the two methods. For fungus except Pneumocystis jirovecii (PJ), conventional tests had a significantly higher sensitivity (P = 0.013) with a similarly high specificity (P = 0.109). The sensitivities for bacteria and fungi could be increased with the combination of the two methods. As for PJ, both the sensitivity (100%) and specificity (99.12%) of mNGS were very high. For viruses, the sensitivity of mNGS was significantly higher (P = 0.021) and the negative predictive value (NPV) was 95.74% (84.27-99.26%). Pulmonary infection complications accounted for 90.30% and bacterium was the most common pathogen whether in single infection (63.43%) or mixed infection (81.08%). The 6-month overall survival (OS) of 88.89% in the early group (mNGS ≤ 7 days) was significantly higher than that of 65.52% (HR 0.287, 95% CI 0.101-0.819, P = 0.006) in the late group (mNGS > 7 days). CONCLUSIONS: mNGS for BALF could facilitate accurate and fast diagnosis for pulmonary complications. Early mNGS could improve the prognosis of patients with pulmonary complications after allo-HSCT. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04051372.

A Stacked FKM/PU Triboelectric Nanogenerator for Discrete Mechanical Energy Harvesting.

To combine the advantages of elastic and nonelastic triboelectric materials, this work proposes a new type of triboelectric nanogenerator (TENG) based on stacking -the stacked FKM/PU TENG. By stacking the elastomer polyurethane (PU) and the nonelastomer fluororubber (FKM), the FKM/PU TENG combines the inherent triboelectric characteristics of both materials and the unique elasticity of PU to achieve an output performance that is much higher than that of the FKM-TENG or the PU-TENG. The maximum instantaneous open-circuit voltage and short-circuit current of the FKM/PU TENG reach 661 V and 71.2 µA, respectively. Under the limiting conditions of 3 Hz and maximum compression, this device can attain a maximum power density of 49.63 W/m3 and light more than 500 LEDs. Therefore, stacking materials with different properties gives the FKM/PU TENG high output performance and great application potential, which can contribute to future development of discrete mechanical energy harvesting.

Impact of Lymphocyte Subsets of Grafts on the Outcome of Haploidentical Peripheral Blood Stem Cell Transplantation.

The contribution of lymphocyte subset composition of the graft on the outcomes following haploidentical peripheral blood stem cell transplantation (haploPBSCT) is not fully elucidated. We retrospectively analyzed 314 patients with hematological malignancies who underwent haploPBSCT from 2016 to 2020 in our center. We obtained a cutoff value of CD3+ T cell dose (2.96 × 108/kg) that separated the risk of II-IV acute graft-versus-host disease (aGvHD) and divided patients into the low CD3+ T cell dose group (CD3+ low) and the high CD3+ T cell dose (CD3+ high) group. Significantly higher incidences of I-IV aGvHD, II-IV aGvHD, and III-IV aGvHD were identified in the CD3+ high group (50.8%, 19.8%, and 8.1% in the high group, 23.1%, 6.0%, and 0.9% in the low group, P < 0.0001, P = 0.002, and P = 0.02, respectively). We found that CD4+ T cell and its naïve and memory subpopulations of grafts had a significant impact on aGvHD (P = 0.005, P = 0.018, and P = 0.044). Besides, we found an inferior reconstitution of natural killer (NK) cells in the CD3+ high group than in the low group within the first-year posttransplant (239 cells/µL vs 338 cells/µL, P = 0.0003). No differences in engraftment, chronic GvHD (cGvHD), relapse rate, transplant-related mortality (TRM), and overall survival (OS) were identified between the two groups. In conclusion, our study found that a high CD3+ T cell dose led to a high risk of aGvHD and inferior reconstitution of NK cells in the haploPBSCT setting. In the future, carefully manipulating the composition of lymphocyte subsets of grafts might reduce the risk of aGvHD and improve the transplant outcome.

Alleviating acid inhibition via bentonite supplementation during acidulated swine manure anaerobic digestion: Performance enhancement and microbial mechanism analysis.

Swine manure is usually transmitted by the "collection-storage-transport" mode of the biogas project. However, this particular application pattern results in high volatile fatty acids (VFAs) concentration due to the long transition time in the "collection-storage-transport" process. In this work, acidulated swine manure anaerobic digestion (AD) with bentonite supplementation was firstly investigated with an expectation of acid alleviation, performance enhancement and microbial mechanism. Results indicated that the methane production rate in the 20 g/L bentonite-added digester was 2.87 fold higher than that of the control digester. Chemical oxygen demand (COD) removal rate was elevated by 140.1% via bentonite supplementation. Besides, the rapid decrease of VFAs and ammonia indicated that bentonite supplementation could offer buffering capacity and alleviate acid inhibition. Microbial community analysis revealed that acetoclastic methanogenesis (Methanosaeta and Methanosarcina) was the predominant methanogenesis pathway in this AD system. Syntrophic acetate oxidation (SAO) bacteria were discovered in the bentonite-added digester, and they converted acetate into H2/CO2 to support hydrogenotrophic methanogenesis. This study could offer guidance for acidulated swine manure AD in the practical biogas project.

The association between the respiratory tract microbiome and clinical outcomes in patients with COPD.

Though it has been widely accepted that infections of the respiratory tract is associated with aetiology of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), more recent techniques have shown emerging evidence on the importance of alterations of diversity and composition of microbiota itself in the disease process. Specifically, these alterations is widely present in COPD patients from a variety of populations, and is associated with severity of disease, frequency of acute exacerbation, as well as prediction of exacerbation. In addition, the microbiota from respiratory tract contributes to disease mechanisms, and more recently have been shown to interact with gut microbiota in a bidirectional way. Therefore, updating progress in the field is crucial as it not only reveals potential underlying mechanisms of the disease, but also highlights the potential utilisation of microbiota as a biomarker for disease prediction and as a target for treatment. In this narrative review, we summarize current updates on microbiota dysbiosis in COPD, including techniques for sampling and analysis of microbiota, recent findings on the presence of microbiota dysbiosis and its correlation with clinical prediction and prognosis of the disease, as well as its potential roles in disease mechanisms. In addition, how gut-lung axis contributes to COPD progression is also discussed. Finally, we addressed the utilisation of prebiotic and probiotic treatment for COPD. Together, we hope to provide useful information to advocate the use of microbial parameters as important tools for diagnosis, treatment and long-term follow-up for COPD patients.

Immune reconstitution and survival of patients after allogeneic hematopoietic stem cell transplantation from older donors.

BACKGROUND: The impact of donor age on the immune reconstitution of patients with hematological malignancies who underwent hematopoietic cell transplantation (HCT) is unclear. METHOD: We retrospectively compared the outcomes of 381 patients who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from 308 donors under 50 years of age and 73 donors over 50 years of age. IVIG was regularly supplemented for patients in the first 3 months post-HCT. RESULTS: The counts of CD8+CD45RA+ naïve T cells were significantly lower in patients of the older donor group than in the younger donor group in the first year after PBSCT (190.6 cells/µl vs. 239.6 cells/µl, p = .018). Patients in the older donor group had significantly fewer CD19+ B cells on day +270 (123.4 cells/µl vs. 183.5 cells/µl, p = .021) and day +365 (169 cells/µl vs. 271.1 cells/µl, p = .01) after PBSCT. Serum IgA (.76 g/L vs. .97 g/L, p < .001) and IgM levels (.75 g/L vs. 1.04 g/L, p < .001) were significantly lower in patients in the older donor group from day +60 to +365 after PBSCT. The EBV reactivation rate within the first 3 months after PBSCT was significantly higher in patients in the older donor group (48.6% vs. 38.3%, p = .034). However, the incidences of CMV reactivation, II-IV acute graft-versus-host disease (aGvHD), chronic GvHD (cGvHD), 3-year relapse rate, 3-year transplant-related mortality (TRM) and 3-year overall survival (OS) were not significantly different between the two groups. CONCLUSION: In conclusion, donors ≥50 years old were associated with inferior immune reconstitution and higher EBV reactivation in patients after PBSCT, but no change in OS.

Low-Dose Anti-Thymocyte Globulin Plus Low-Dose Posttransplant Cyclophosphamide as an Effective Regimen for Prophylaxis of Graft Versus Host Disease After Haploidentical Peripheral Blood Stem Cell Transplantation With Maternal/Collateral Related Donors.

Maternal and collateral donors were associated with a higher incidence of graft-versus-host disease (GvHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). A more effective regimen for GvHD prophylaxis after haplo-HSCT with maternal/collateral donors needed to be explored. A retrospective study was performed on 62 patients after haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with maternal/collateral donors, which included 35 patients with low-dose antithymocyte globulin (ATG) plus low-dose posttransplant cyclophosphamide-based (low-dose ATG/PTCy-based) and 27 with ATG-based regimens for GvHD prophylaxis. The 180-day cumulative incidences (CIs) of grades II-IV and III-IV acute GvHD (aGvHD) were 17.7% and 6.8% in low-dose ATG/PTCy-based group, which were significantly lower than that in ATG-based group (55.4% and 31.9%) (P = 0.003 for grade II-IV and P = 0.007 for III-IV aGvHD). In low-dose ATG/PTCy-based group, the 1-year overall survival (OS) and relapse-free survival (RFS) were 80.0%and 80.4%, which were higher than that in ATG-based group with OS of 59.4% and RFS of 62.0%. In multivariate analysis, the low-dose ATG/PTCy-based regimen significantly reduced the risk of grade II-IV (HR = 0.357; P = 0.049) and grade III-IV aGvHD (HR = 0.190; P = 0.046) as an independent risk factor. The results suggested that the low-dose ATG/PTCy-based regimen could effectively prevent the occurrence of aGvHD after haplo-PBSCT with maternal/collateral donors compared with the ATG-based regimen.

Total Body Irradiation-Based Conditioning Regimen Improved the Survival of Adult Patients With T-Cell Lymphoblastic Lymphoma After Allogeneic Peripheral Blood Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the consolidation modalities for adult patients with T-cell lymphoblastic lymphoma (T-LBL). However, the optimal conditioning regimen needs to be explored. In the present study, 40 patients with T-LBL undergoing allo-HSCT were retrospectively analyzed, including 23/40 (57.5%) with total body irradiation (TBI)-based conditioning regimen and 17/40 (42.5%) with busulfan (BU)-based regimen. TBI-based regimen significantly increased the cumulative incidence (CI) of grade II to IV acute graft-versus-host disease (aGvHD) as compared with BU-based regimen (13.0% vs 0%, P = 0.000). The relapse risk was significantly lowered in TBI-based group with a 2-year CI of relapse (CIR) of 9.1% as compared with that of 49.6% in BU-based group (P = 0.008). The 1-year and 2-year non-relapse mortalities (NRMs) for all patients were 5.0% and 10.3%, respectively. The 1-year and 2-year NRMs were 8.9% and 16.0% in TBI-based group, and 0.00% and 0.00% in BU-based group (P = 0.140). The 2-year probabilities of overall survival (OS) and relapse-free survival (RFS) were 83.0% [95% confidence interval, 63.4%-100%] and 74.0% (95% confidence interval, 54.4%-93.6%) in TBI-based group, which were higher than that of 35.0% (95% confidence interval, 0.0%-72.2%) and 50.0% (95% confidence interval, 24.5%-75.4%) in BU-based group, respectively (P = 0.020 for OS and P = 0.081 for RFS). In multivariate analysis, TBI-based regimen significantly reduced the risk of relapse [subdistribution hazard ratio (SHR) = 0.030, 95% CI, 0.002-0.040, P = 0.000] and improved the OS [hazard ratio (HR) 0.121, 95% CI, 0.021-0.683, P = 0.017] as an independent prognostic factor. These results suggested that TBI-based regimen might be an optimal choice for adult patients with T-LBL undergoing allo-HSCT.

Epstein-Barr Virus Encephalitis and Disseminated Adenovirus Infection after Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation for a Patient with Ph-Like Acute Lymphoblastic Leukemia.

Viral reactivation or infections are common complications after allogeneic hematopoietic stem cell transplantation, especially in haploidentical transplantation. Here, we presented a young patient with Ph-like acute lymphoblastic leukemia who suffered Epstein-Barr virus (EBV) encephalitis and disseminated adenovirus (ADV) infection after haploidentical peripheral blood (PB) stem cell transplantation. The patient was a 16-year-old boy and received PB stem cells from his HLA-haploidentical matched father. On day +44 after transplantation, he had viremia with cytomegalovirus, and EBV was diagnosed as EBV encephalitis after 2 weeks. On day +117, he had disseminated ADV infection and fulminant ADV hepatitis. It is very rare that successive EBV encephalitis and fulminant ADV hepatitis are present in the same patient. We summarized risk factors, clinical manifestations, diagnostic criteria, and effective treatments about EBV encephalitis and disseminated ADV infection. We try to enhance our understanding of the prevention, diagnosis, and potential treatment of EBV and ADV disease by reviewing the entire procedure.

Immune reconstitution and survival of patients with parvovirus B19 related pure red cell aplasia after haplo-PBSCT.

Parvovirus B19 (PvB19) infection and PvB19 related pure red cell aplasia (PRCA) in recipients with allogeneic hematopoietic stem cell transplantation have been reported sporadically. However, clinical studies with large sample sizes are lacking, especially in patients undergoing HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). In addition, clinical features, immune reconstitution, and outcomes of these patients are not clear. We conducted a retrospective analysis of 164 patients who received haplo-PBSCT with low-dose anti-thymocyte globulin (ATG) plus low-dose posttransplant cyclophosphamide (PTCy)-based regimen as graft-versus-host disease (GVHD) prophylaxis. We analyzed the incidence of PvB19 related PRCA and compared the clinical characteristics, immune reconstitution, incidence of GVHD, relapse rate, and survival between patients with and without PvB19 related PRCA. A total of 14 (8.5%) recipients developed PvB19 related PRCA after a median of 5.3 months after haplo-PBSCT. These patients with PvB19 related PRCA had slower immune reconstitution, but similar incidences of GVHD, relapse rate, and overall survival compared with recipients without PvB19 related PRCA. PvB19 related PRCA indicated relative delayed and poor immune reconstitution of the recipients early after haplo-PBSCT. PvB19 related PRCA had no effects on GVHD, relapse, and survival.

Lower Absolute Lymphocyte Count Before Conditioning Predicts High Relapse Risk in Patients After Haploidentical Peripheral Blood Stem Cell Transplantation With Low Dose Anti-Thymocyte Globulin/Post-Transplant Cyclophosphamide for GvHD Prophylaxis.

Standard anti-thymocyte globulin (ATG) weight-based dosing often resulted in highly variable ATG exposure, which had profound effects on relapse and survival, especially in recipients with relatively low absolute lymphocyte count (ALC) before conditioning. Data regarding rabbit ATG pharmacokinetics and pharmacodynamics in the setting of HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) is lacking. We conducted a retrospective study on 90 consecutive patients who underwent haplo-PBSCT with low dose rabbit ATG (5 mg/kg) plus low dose post-transplant cyclophosphamide (50 mg/kg) based regimen for graft-versus-host disease (GvHD) prophylaxis. We compared serum concentration of ATG and post-transplant results between patients with ALC<500/µl and ALC≥500/µl before conditioning. Patients with ALC<500/µl had higher ATG concentrations, delayed immune reconstitution, lower incidence of grade II-IV acute GvHD (0 vs. 19.42%, P = 0.043), higher risk of Epstein-Barr virus infection within 100 days post-transplant (47.78% vs. 22.22%, P = 0.020) and 1-year relapse rate (33.33% vs.11.59%, P = 0.041), and lower 1-year overall survival (OS) (52.38% vs.79.71%, P = 0.004), 1-year relapse free survival (RFS) (47.62% vs. 75.36% for RFS, P = 0.014), and 1-year GvHD free relapse-free survival (GRFS) (42.89% vs. 65.22%, P = 0.043). ALC<500/µl before conditioning was a significant poor risk factor for relapse, OS, RFS, and GRFS.

Key microbial clusters and environmental factors affecting the removal of antibiotics in an engineered anaerobic digestion system.

To identify the key microbial clusters and influencing factors involved in antibiotic removal from engineered anaerobic digestion (AD) systems, the dynamic characteristics of antibiotics, physiochemical factors, microbial communities and functional genes were investigated by 16S rRNA and metagenome sequencing. The results showed that antibiotic removal occurred mainly in the first 21 days, and sulfonamides had the highest removal rate. The key microbial clusters related to the biodegradation of antibiotics consisted mainly of Firmicutes and Bacteroidetes. The key enzymes consisted of deaminases, peptidases, C-N ligases, decarboxylases and alkyl-aryl transferases. Structural equation modelling indicated that low concentrations of propionic acid promoted the biodegradation activities of key microbial clusters in the first 21 days, but their activities were inhibited by the accumulated propionic acid after 21 days. Thus, propionic acid should be regulated in engineered AD systems to prevent the adverse effect of acid inhibition on antibiotic-degrading bacteria.

Antibiotic degradation dominates the removal of antibiotic resistance genes during composting.

To identify the key hosts involved in horizontal gene transfer (HGT) and vertical gene transfer (VGT) of antibiotic resistance genes (ARGs) and to determine the extent to and ways in which environmental properties contribute to ARG removal, the changes in ARG profile and key hosts during biogas residue and pig manure composting were investigated using metagenomic sequencing coupled with network analysis. Composting significantly reduced the abundances of ARGs other than bacA. Seventy and 41 hosts from Firmicutes, Actinobacteria, Proteobacteria and Bacteroidetes were associated with HGT and VGT, respectively. The key environmental properties were determined using structural equation modelling. Antibiotics directly affected HGT and determined ARG removal. Temperature indirectly affected HGT, mainly by influencing the degradation of antibiotics. BacA was associated only with hosts involved in VGT, which may lead to its low removal rate. These findings specify the priority and pathway of antibiotics and temperature affecting ARG profile.

Low-dose antithymocyte globulin plus low-dose posttransplant cyclophosphamide combined with cyclosporine and mycophenolate mofetil for prevention of graft-versus-host disease after HLA-matched unrelated donor peripheral blood stem cell transplantation.

The standard regimens for graft-versus-host disease (GvHD) prophylaxis in matched unrelated donor (MUD) transplantation were based on antithymocyte globulin (ATG) in combination with calcineurin inhibitors (CNIs). To improve the efficiency of GvHD prophylaxis in MUD peripheral blood stem cell transplantation (MUD-PBSCT), 51 patients with hematological malignancies received a novel regimen for GvHD prophylaxis, which is composed of low dose of ATG (5 mg/kg) plus low-dose posttransplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy) combined with cyclosporine A (CsA) and mycophenolate mofetil (MMF). The cumulative incidences (CIs) of grades I-IV and II-IV acute GvHD (aGvHD) were 14.5% (95% CI, 9.4-19.6%) and 6.2% (95% CI, 2.8-9.6%) within 100 days after transplantation, respectively. The CI of mild-to-moderate chronic GvHD (cGvHD) within 1 year was 11.5% (95% CI, 6.6-16.4%). The 1-year probabilities of GvHD and relapse-free survival, relapse-free survival, and over survival were 70.6% (95% CI, 64.2-77.0%), 76.5% (95% CI, 70.6-82.4%), and 82.0% (95% CI, 76.5-87.5%), respectively. The CIs of CMV and EBV reactivation by day 180 were 10.4% (95% CI, 1.5-19.4%) and 8.3% (95% CI, 0.2-16.4%), respectively. The results suggested that low-dose ATG/PTCy combined with CsA/MMF as GvHD prophylaxis in MUD-PBSCT had promising activity.

Comparison of microbial community structures between mesophilic and thermophilic anaerobic digestion of vegetable waste.

The anaerobic digestion performance correlates with the functional microbial community. Mesophilic and thermophilic digestions of vegetable waste were conducted, and dynamics of the microbial community were investigated. The mesophilic and thermophilic collapsed stages occurred at organic loading rates of 1.5 and 2.0 g VS/(L d) due to the accumulation of volatile fatty acids with final concentrations of 2276 and 6476 mg/L, respectively. A high concentration of volatile fatty acids caused the severe inhibition of methanogens, which finally led to the imbalance between acetogenesis and methanogenesis. The mesophilic digestion exhibited a higher microbial diversity and richness than the thermophilic digestion. Syntrophic acetate-oxidizing coupled with hydrogenotrophic methanogenesis was the dominant pathway in the thermophilic stable system, and acetoclastic methanogenesis in the mesophilic stable system. The dominant acidogens, syntrophus, and methanogens were unclassified_f__Anaerolineaceae (8.68%), Candidatus_Cloacamonas (19.70%), Methanosaeta (6.10%), and Methanosarcina (4.08%) in the mesophilic stable stage, and Anaerobaculum (12.59%), Syntrophaceticus (4.84%), Methanosarcina (30.58%), and Methanothermobacter (3.17%) in thermophilic stable stage. Spirochaetae and Thermotogae phyla were the characteristic microorganisms in the mesophilic and thermophilic collapsed stages, respectively. These findings provided valuable information for the deep understanding of the difference of the microbial community and methane-producing mechanism between mesophilic and thermophilic digestion of vegetable waste.