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Abstract In herpesvirus, the terminase subunit pUL15 is involved in cleavage of the viral genome concatemers in the nucleus. Previous studies have shown that herpes simplex virus 1 (HSV-1) pUL15 can enter the nucleus without other viral proteins and help other terminase subunits enter the nucleus. However, this study revealed that duck plague virus (DPV) pUL15 cannot localize independently to the nucleus and can only be localized in the nucleus in the presence of pUL28 and pUL33. However, the data suggested the presence of a potential nuclear localization signal (NLS) in DPV pUL15, which is important for the localization of the terminase subunits. Subsequently, several single-point mutants were constructed to identify the vital amino acids within the NLS. The conserved amino acids K187, R188, and K190 are critical for the nuclear localization of pUL15, pUL28, and pUL33 but not for their interaction. Furthermore, corresponding recombinant viruses were constructed. The results revealed that the mutations rUL15K187Q, rUL15K188Q and rUL15K190Q had an obvious influence on concatemeric genome cleavage, but only K190Q significantly affected the production of progeny virions. These findings indicate that the NLS is important for the functions of DPV pUL15. Overall, a potential NLS and the key amino acids in DPV pUL15 were identified. Mutations in K187, K188 and K190 affected the cleavage of the concatemeric genome, but only mutations in K190 had an obvious effect on viral proliferation.

Abstract Background Cerebral venous sinus thrombosis (CVST), a serious cerebrovascular and neurological emergency, is common in pregnant individuals and accounts for approximately 0.5–1.0% of all cerebrovascular diseases. However, CVST with cryptococcal meningoencephalitis in immunocompetent pregnant patients is rare. Case presentation A 30-year-old woman who was 33 weeks pregnant presented with recurrent dizziness, headache, and vomiting as the main clinical manifestations, all of which were initially nonspecific. After assessment of the cerebrospinal fluid, skull computerized tomography, magnetic resonance imaging, and other laboratory and imaging examinations, the patient was diagnosed with secondary pregnancy-related CVST with cryptococcal meningoencephalitis. Despite receiving potent anticoagulant and antifungal treatment, the patient’s condition deteriorated, and the patient’s family opted to cease treatment. Conclusions We present a rare case of CVST with cryptococcal meningoencephalitis in an immunocompetent pregnant patient. The difficulty of diagnosing and treating secondary pregnancy-related CVST caused by cryptococcal meningoencephalitis, as well as the great challenges faced at present are highlighted. One crucial lesson from the present case is that when clinical and imaging signs are unusual for CVST during pregnancy, it is essential to account for the possibility of other central nervous system (CNS) diseases, such as CNS infections with Cryptococcus, which may cause CVST.

Chlorophyll-a (Chl a) is an important indicator of algal biomass frequently used to evaluate the severity of cultural eutrophication. Identifying the key covariates of Chl a concentrations is essential to understand the mechanisms that drive eutrophication and to develop forecasting tools that guide the restoration process. In this study, we present a novel ensemble modeling framework founded upon the complementary features of Random Forest (RF) and Generalized Additive modeling (GAMs). A series of RF models are first developed to forecast Chl a concentrations based on the antecedent values of a multitude of environmental predictors. GAMs are then used to explore the presence of non-linearities in the seasonal relationships between Chl a and the identified predictors. The optimal RF models using a 0–8 day time lag displayed high predictive skills with adjusted R2 values consistently above 0.80. Analyses of the RF models revealed that the modulating factors of Chl a display significant seasonality. Dissolved oxygen (DO) and turbidity were the key covariates of Chl a in the spring, while the water level fluctuations predominantly regulated phytoplankton biomass in the summer and winter. The occurrence and severity of algal blooms in the summer and autumn were associated with threshold levels of 0.06 and 1.50 mg/L for total phosphorus (TP) and total nitrogen (TN) concentrations, respectively. These results reveal the potential of the introduced modeling framework to shed light on the regulatory factors of algal biomass as well as to establish real-time predictions in the Nanji wetland waters of Poyang Lake.

Background Symptom networks offer a theoretical basis for developing personalised and precise symptom management strategies. However, symptom networks in lymphoma patients during chemotherapy have been rarely reported. This study intends to establish contemporaneous symptom networks in lymphoma patients during chemotherapy and explore the centrality indices and density in these symptom networks.Methods and analysis This is a single-centre prospective cross-sectional study. A total of 315 lymphoma patients admitted to the Lymphoma Department of Shanxi Bethune Hospital since 1 June 2024 will be selected as the study subjects. The patient-reported outcome measures of General Data Questionnaire and Lymphoma Symptom Assessment Scale will be assessed. R package will be used to construct a contemporaneous symptom network, explore the relationship between core and analysed symptoms and analyse the predictive role of network density on patient prognosis.Ethics and dissemination This study adheres to the principles of the Declaration of Helsinki and relevant ethical guidelines. Ethical approval has been obtained from Shanxi Bethune Hospital Ethics Committee (approval number: YXLL-2023-186). The final outcomes will be published in a peer-reviewed journal and disseminated through a conference.

Abstract Background Droplet digital PCR (ddPCR) is widely applied to monitor measurable residual disease (MRD). However, there are limited studies on the feasibility of ddPCR-MRD monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially targeting multiple molecular markers simultaneously. Methods Our study collected samples from patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) in complete remission after allo-HSCT between January 2018 and August 2021 to evaluate whether posttransplant ddPCR-MRD monitoring can identify patients at high risk of relapse. Results Of 152 patients, 58 (38.2%) were MRD positive by ddPCR within 4 months posttransplant, with a median variant allele frequency of 0.198%. The detectable DTA mutations (DNMT3A, TET2, and ASXL1 mutations) after allo-HSCT were not associated with an increased risk of relapse. After excluding DTA mutations, patients with ddPCR-MRD positivity had a significantly higher cumulative incidence of relapse (CIR, 38.7% vs. 9.7%, P

Abstract Background The prognostic significance of myelofibrosis (MF) grade in patients with myelodysplastic syndrome (MDS) following an allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains elusive. Methods We retrospectively analyzed data from 153 patients with MDS who underwent allo-HSCT and divided the patients into the MF-0/1 (N = 119) and MF-2/3 (N = 34) cohorts to explore the impact of MF on outcomes of allo-HSCT. Results The 2-year rates of relapse, non-relapse mortality (NRM), overall survival (OS), and progression-free survival (PFS) were 10.9% (95% confidence interval [CI] 5.9%–17.7%), 16.3% (95% CI 10.2%–23.6%), 76.6% (95% CI 69.0%–85.1%), and 72.8% (95% CI 65.0%–81.5%) in the MF-0/1 cohort, and 16.9% (95% CI 5.8%–32.9%), 14.7% (95% CI 5.3%–28.7%), 71.8% (95% CI 57.6%–89.6%), and 68.4% (95% CI 53.6%–87.2%) in the MF-2/3 cohort, respectively. No significant difference in the outcomes of allo-HSCT was observed between the two cohorts. Both univariate and multivariate analyses confirmed that MF-2/3 in patients with MDS had no effect on the prognosis of transplantation. In addition, major/bidirectional ABO blood type between donors and recipients was an independent risk factor for OS (hazard ratio [HR], 2.55; 95% CI 1.25–5.21; P = 0.010) and PFS (HR, 2.21; 95% CI 1.10–4.42; P = 0.025) in the multivariate analysis. In the subgroup of patients diagnosed with MDS with increased blasts (MDS-IB), it was consistently demonstrated that the clinical outcomes of the MF-2/3 cohort were comparable with those of the MF-0/1 cohort. The risk factors for OS and PFS in patients with MDS-IB were non-complete remission at transplantation and major/bidirectional ABO blood type. Conclusions In conclusion, MF grade had no significant effect on prognosis of allo-HSCT in patients diagnosed with MDS. Major/bidirectional ABO blood type should be carefully considered in the context of more than one available donor.

Abstract Single-atom catalysts show excellent catalytic performance because of their coordination environments and electronic configurations. However, controllable regulation of single-atom permutations still faces challenges. Herein, we demonstrate that a polarization electric field regulates single atom permutations and forms periodic one-dimensional Au single-atom arrays on ferroelectric Bi4Ti3O12 nanosheets. The Au single-atom arrays greatly lower the Gibbs free energy for CO2 conversion via Au-O=C=O-Au dual-site adsorption compared to that for Au-O=C=O single-site adsorption on Au isolated single atoms. Additionally, the Au single-atom arrays suppress the depolarization of Bi4Ti3O12, so it maintains a stronger driving force for separation and transfer of photogenerated charges. Thus, Bi4Ti3O12 with Au single-atom arrays exhibit an efficient CO production rate of 34.15 µmol·g−1·h−1, ∼18 times higher than that of pristine Bi4Ti3O12. More importantly, the polarization electric field proves to be a general tactic for the syntheses of one-dimensional Pt, Ag, Fe, Co and Ni single-atom arrays on the Bi4Ti3O12 surface.

Abstract Acquired resistance to chemotherapy is one of the major causes of mortality in advanced nasopharyngeal carcinoma (NPC). However, effective strategies are limited and the underlying molecular mechanisms remain elusive. In this study, through transcriptomic profiling analysis of 23 tumor tissues, we found that NOTCH3 was aberrantly highly expressed in chemoresistance NPC patients, with NOTCH3 overexpression being positively associated with poor clinical outcome. Mechanistically, using an established NPC cellular model, we demonstrated that enhancer remodeling driven aberrant hyperactivation of NOTCH3 in chemoresistance NPC. We further showed that NOTCH3 upregulates SLUG to induce chemo-resistance of NPC cells and higher expression of SLUG have poorer prognosis. Genetic or pharmacological perturbation of NOTCH3 conferred chemosensitivity of NPC in vitro and overexpression of NOTCH3 enhanced chemoresistance of NPC in vivo. Together, these data indicated that genome-wide enhancer reprogramming activates NOTCH3 to confer chemoresistance of NPC, suggesting that targeting NOTCH3 may provide a potential therapeutic strategy to effectively treat advanced chemoresistant NPC.

Objectives: This research aimed to explore the prevalence and determinants of overweight, obesity, and central obesity in Shenmu City, Shaanxi Province, China and to offer guidance for preventative health measures. Methods: We conducted a multi-stage, stratified random sampling survey among 4,565 residents of Shenmu City. Data collection included questionnaires and anthropometric assessments to gather socio-demographic data and to identify cases of overweight, obesity, and central obesity. Multivariable logistic regression analysis was utilized to assess the association between various factors and these conditions. Results: The observed prevalence rates for overweight, obesity, central obesity, and the combination of overweight/obesity with central obesity were 39.9%, 18.2%, 48.0%, 32.8%, and 22.8%, respectively. Notably, the incidence of these conditions was significantly higher in men compared to women. The prevalence of overweight and obesity initially increased and then decreased with age, whereas the prevalence of central obesity consistently rose. Furthermore, a higher educational level correlated with lower prevalence rates. Additionally, our analysis indicated that hypertension, dyslipidemia, and hyperuricemia are risk factors for these conditions. Conclusions: The findings of this study offer crucial insights for formulating effective strategies to prevent and manage obesity in Shenmu City.

Urban rivers and lakes are major components of inland waters. A deeper understanding of how carbon dioxide (CO2) emissions are impacted in urban waters is important for quantifying the contributions of urban waters to the global carbon budget. Acidic polysaccharides (APS) are a major component of the carbon pool, though there is still much uncertainty associated with CO2 concentrations and fluxes. Here, we measured the dissolved APS (DAPS), particulate APS (PAPS), and CO2 concentrations and fluxes in a typical urban river (the Ganjiang River) and two lakes (Xiang Lake and Qingshan Lake) in China, and assessed the impact of different APS fractions on CO2 concentrations and fluxes. Our results show abundant DAPS and PAPS in urban waters, with PAPS being the main form in winter while DAPS the main component in other seasons. The Ganjiang River and the urban lakes were supersaturated with CO2 at concentrations of 35.67 ± 19.99 μmol·L−1 & 27.79 ± 17.52 μmol·L−1 and emissions of 64.52 ± 53.38 mmol·(m2 d)−1& 36.56 ± 56.97 mmol·(m2 d)−1 from river and lake waters, respectively. Linear mixed-effects model analysis further revealed that increased DAPS concentration led to significantly higher CO2 concentrations and fluxes, whereas PAPS exhibited a negative influence on CO2 concentrations and fluxes in the urban lakes. Our work provides deeper insight into CO2 evasion in inland freshwater ecosystems as well as carbon neutrality in urban waters.

Abstract Background Enhancer of zeste homolog 2 (EZH2), the key catalytic subunit of polycomb repressive complex 2 (PRC2), is overexpressed and plays an oncogenic role in various cancers through catalysis-dependent or catalysis-independent pathways. However, the related mechanisms contributing to ovarian cancer (OC) are not well understood. Methods The levels of EZH2 and H3K27me3 were evaluated in 105 OC patients by immunohistochemistry (IHC) staining, and these patients were stratified based on these levels. Canonical and noncanonical binding sites of EZH2 were defined by chromatin immunoprecipitation sequencing (ChIP-Seq). The EZH2 solo targets were obtained by integrative analysis of ChIP-Seq and RNA sequencing data. In vitro and in vivo experiments were performed to determine the role of EZH2 in OC growth. Results We showed that a subgroup of OC patients with high EZH2 expression but low H3K27me3 exhibited the worst prognosis, with limited therapeutic options. We demonstrated that induction of EZH2 degradation but not catalytic inhibition profoundly blocked OC cell proliferation and tumorigenicity in vitro and in vivo. Integrative analysis of genome-wide chromatin and transcriptome profiles revealed extensive EZH2 occupancy not only at genomic loci marked by H3K27me3 but also at promoters independent of PRC2, indicating a noncanonical role of EZH2 in OC. Mechanistically, EZH2 transcriptionally upregulated IDH2 to potentiate metabolic rewiring by enhancing tricarboxylic acid cycle (TCA cycle) activity, which contributed to the growth of OC. Conclusions These data reveal a novel oncogenic role of EZH2 in OC and identify potential therapeutic strategies for OC by targeting the noncatalytic activity of EZH2.

Abstract The success of allogeneic hematopoietic stem cell transplant for hematological malignancies is heavily dependent on the availability of suitable donors. Haploidentical donor (HID) and matched sibling donor (MSD) are two important donor options providing faster and easier sources of stem cells, however, due to confounding factors present in most retrospective studies, the validity of comparing outcomes between these two donor types remains uncertain. We conducted a post-hoc analysis of a prospective clinical trial (trial registration: Chinese Clinical Trial Registry; #ChiCTR-OCH-12002490; registered 22 February 2012; https://www.chictr.org.cn/showproj.aspx?proj=7061 ) to compare outcomes of HID versus MSD peripheral blood stem cell-derived transplants in patients with hematologic malignancies between 2015 and 2022. All HID-receiving patients had antithymocyte globulin-based conditioning. Propensity score matching was employed to minimize potential confounding factors between the two cohorts. A total of 1060 patients were initially reviewed and then 663 patients were ultimately included in the analysis after propensity score matching. The overall survival, relapse-free survival, non-relapse mortality rate and cumulative incidence of relapse were similar between HID and MSD cohorts. Subgroup analysis revealed that patients with positive measurable residual disease in first complete remission may have better overall survival with an HID transplant. The present demonstrated that haploidentical transplants can provide outcomes comparable to conventional MSD transplants, and HID should be recommended as one of the optimal donor choices for patients with positive measurable residual disease in first complete remission.

Summary: Background: Although chimeric antigen receptor-modified T cells (CAR T) cell therapy has been widely reported in improving the outcomes of B-cell acute lymphoblastic leukemia (B-ALL), less research about the feasibility and safety of donor-derived CAR T after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was reported. Methods: This phase 1 clinical trial aims to evaluate safety and efficacy of donor-derived anti-CD19 CAR T cells (GC007g) in B-ALL patients who relapsed after allo-HSCT. This trial is registered with ClinicalTrials.gov, NCT04516551. Findings: Between 15 March 2021 and 19 May 2022, fifteen patients were screened, three patients were excluded due to withdraw of consent, donor's reason, and death, respectively. Patients received donor-derived CAR T cells infusions at 6 × 105/kg (n = 3) or 2 × 106/kg (n = 6) dose level. The median time from HSCT to relapse was 185 days (range, 81–2063). The median age of patients was 31 years (range 21–48). Seven patients (77.8%) had BCR-ABL fusion gene. CAR T cells expanded in vivo and the median time to reach Cmax was 9 days (range, 7–11). One patient had hyperbilirubinemia after GC007g infusion which was defined as a dose-limiting toxicity. All patients experienced CRS and hematological adverse events. Three patients had acute graft-versus-host-disease (grade I, n = 1; grade II, n = 1; grade IV, n = 1) and all resolved after treatment. They received CAR T cells from matched sister, haploidentical matched father and sisiter, respectively. At 28 days after infusion, all patients achieved complete remission with/without incomplete hematologic recovery (CRi/CR) with undetectable MRD. At a median follow-up of 475 days (range 322–732), seven patients remained in CR/CRi while two had CD19-negative relapse. The overall response rates (ORR) were 100% (9/9), 88.9% (8/9), and 75% (6/8) at 3 month, 6 month, and 12 month, respectively. The 1-year progression-free and overall survival were 77.8% and 85.7%, respectively. Interpretation: GC007g expanded and induced durable remission in patients with B-ALL relapsed after allo-HSCT, with manageable safety profiles. Funding: Gracell Biotechnologies Inc.

KMT2A rearrangement ( KMT2A -r) in patients with acute myeloid leukemia (AML) is associated with poor outcomes; the prognostic factors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear. We investigated 364 adults with AML who underwent allo-HSCT between April 2016 and May 2022, and 45 had KMT2A -r among them. Propensity score analysis with 1:1 matching and the nearest neighbor matching method identified 42 patients in KMT2A -r and non– KMT2A -r cohorts, respectively. The 2-year overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and non-relapsed mortality rates of patients with KMT2A -r ( n = 45) were 59.1%, 49.6%, 41.5%, and 8.9%, respectively. Using propensity score matching, the 2-year OS rate of patients with KMT2A -r ( n = 42) was lower than that of those without KMT2A -r ( n = 42; 56.1% vs 88.1%, P = 0.003). Among patients with KMT2A -r ( n = 45), the prognostic advantage was exhibited from transplantation in first complete remission (CR1) and measurable residual disease (MRD) negative, which was reflected in OS, RFS, and CIR ( P < 0.001, P < 0.001, and P = 0.002, respectively). Furthermore, patients with AF6 had poorer outcomes than those with AF9 , ELL , and other KMT2A -r subtypes ( P = 0.032, P = 0.001, and P = 0.001 for OS, RFS, and CIR, respectively). However, no differences were found in the OS, RFS, and CIR between patients with KMT2A -r with and without mutations (all P > 0.05). Univariate and multivariate analyses revealed that achieving CR1 MRD negative before HSCT was a protective factor for OS [hazard ratio (HR) = 0.242, P = 0.007], RFS (HR = 0.350, P = 0.036), and CIR (HR = 0.271, P = 0.021), while AF6 was a risk factor for RFS (HR = 2.985, P = 0.028) and CIR (HR = 4.675, P = 0.004). The prognosis of patients with KMT2A -r AML was poor, particularly those harboring AF6 -related translocation; however, it is not associated with the presence of mutations. These patients can benefit from achieving CR1 MRD negative before HSCT.

Abstract Background Natural killer/T-cell lymphoma (NKTL) is a rare type of aggressive and heterogeneous non-Hodgkin's lymphoma (NHL) with a poor prognosis and limited therapeutic options. Therefore, there is an urgent need to exploit potential novel therapeutic targets for the treatment of NKTL. Histone deacetylase (HDAC) inhibitor chidamide was recently approved for treating relapsed/refractory peripheral T-cell lymphoma (PTCL) patients. However, its therapeutic efficacy in NKTL remains unclear. Methods We performed a phase II clinical trial to evaluate the efficacy of chidamide in 28 relapsed/refractory NKTL patients. Integrative transcriptomic, chromatin profiling analysis and functional studies were performed to identify potential predictive biomarkers and unravel the mechanisms of resistance to chidamide. Immunohistochemistry (IHC) was used to validate the predictive biomarkers in tumors from the clinical trial. Results We demonstrated that chidamide is effective in treating relapsed/refractory NKTL patients, achieving an overall response and complete response rate of 39 and 18%, respectively. In vitro studies showed that hyperactivity of JAK-STAT signaling in NKTL cell lines was associated with the resistance to chidamide. Mechanistically, our results revealed that aberrant JAK-STAT signaling remodels the chromatin and confers resistance to chidamide. Subsequently, inhibition of JAK-STAT activity could overcome resistance to chidamide by reprogramming the chromatin from a resistant to sensitive state, leading to synergistic anti-tumor effect in vitro and in vivo. More importantly, our clinical data demonstrated that combinatorial therapy with chidamide and JAK inhibitor ruxolitinib is effective against chidamide-resistant NKTL. In addition, we identified TNFRSF8 (CD30), a downstream target of the JAK-STAT pathway, as a potential biomarker that could predict NKTL sensitivity to chidamide. Conclusions Our study suggests that chidamide, in combination with JAK-STAT inhibitors, can be a novel targeted therapy in the standard of care for NKTL. Trial registration: ClinicalTrials.gov, NCT02878278. Registered 25 August 2016, https://clinicaltrials.gov/ct2/show/NCT02878278

Abstract Natural killer/T‐cell lymphoma (NKTL) is an uncommon malignancy with poor prognosis and limited therapeutic options. Activating mutations of signal transducer and activator of transcription 3 (STAT3) are frequently found in patients with NKTL, suggesting that targeted inhibition of STAT3 is a potential therapeutic option for this disease. Here, we have developed a small molecule drug WB737 as a novel and potent STAT3 inhibitor that directly binds to the STAT3‐Src homology 2 domain with high affinity. In addition, the binding affinity of WB737 to STAT3 is 250‐fold higher than STAT1 and STAT2. Interestingly, WB737 is more selective for NKTL with STAT3‐activating mutations in terms of growth inhibition and apoptotic induction when compared with Stattic. Mechanistically, WB737 inhibits both canonical and noncanonical STAT3 signaling via suppression of STAT3 phosphorylation at Tyr705 and Ser727, respectively, thereby inhibiting the expression of c‐Myc and mitochondria‐related genes. Moreover, WB737 inhibited STAT3 more potently than Stattic, resulting in a significant antitumor effect with undetectable toxicity, followed by almost complete tumor regression in an NKTL xenograft model harboring a STAT3‐activating mutation. Taken together, these findings provide preclinical proof‐of‐concept for WB737 as a novel therapeutic strategy for the treatment of NKTL patients with STAT3‐activating mutations.

Graphene oxide (GO) films mixed with polyethylenimine (PEI) were prepared by a layer-by-layer assembly (LBL) method, in which the GO component is then converted to reduced GO (rGO) in situ through an electron transfer interaction with a polyoxometalate (POM) that is assembled on the outer surface. With this, devices were manufactured by spreading composite films of (PEI/rGO)n-POM with different numbers of PEI/rGO layers on ITO substrates. Cyclic voltammetry (CV) reveals that the catalytic activity for H2O2 of (PEI/rGO)n-POM films was significantly higher than that of similar films of (PEI/GO)n/PEI/POM manufactured LBL with the same number of layers, although the catalyst POM content of (PEI/rGO)n-POM was only half that of (PEI/GO)n/PEI/POM. The catalytic activity of (PEI/rGO)n-POM films first increases and then decreases as the number of PEI/rGO layers increases. The result shows that (PEI/rGO)3-POM films with three PEI/rGO layers exhibit the highest efficiency. Amperometric measurements of the (PEI/rGO)3-POM films showed improved current response, high sensitivity, wide linear range, low detection limit, and fast response for H2O2 detection. The enhanced catalytic property of (PEI/rGO)n-POM films is attributed to the electron transfer interaction and electrostatic interaction between POM and rGO.

We present the design and synthesis of two novel isostructural metalloring organic frameworks (MROFs) {[(Me2NH2)1.25(H3O)4.25Na1.5X2(μ2-OH)(H2O)(SIP)4]n·xsol} (FUT-2-X, X = Eu and Sm), which are composed of the sulfonate–carboxylate ligand 5-sulfoisophthalic acid monosodium salt (NaH2SIP) and an unprecedented lanthanide–sodium metalloring [X4Na4(H2O)(SIP)2, X = Eu and Sm]. The two MROFs possess channel walls decorated with uncoordinated sulfonic acid groups and filled with abundant guest molecules residing within the framework, which support the proton conductivity of the materials by expanding the intermolecular hydrogen bonding network. FUT-2-Eu exhibits exceptional proton conductivity over a wide temperature range, achieving conductivity from 1.91 × 10−5 S cm−1 (−40 °C) to 2.65 × 10−3 S cm−1 (90 °C). Thanks to the dominant role of the additional guest H2O molecules in FUT-2-Eu's channels, which facilitate the formation of hydrogen-bonded networks for ultra-fast proton transfer with low energy barriers, FUT-2-Eu outperforms FUT-2-Sm in both the operating temperature range and proton conductivity. It is worth noting that FUT-2-Eu has the widest operating temperature range among proton conduction MROF materials. Furthermore, FUT-2-Eu can be considered as an excellent luminescence sensor with high sensitivity (KSV = 1.66 × 104 L mol−1) and a low detection limit (3.64 μM) for detecting Fe3+. [ABSTRACT FROM AUTHOR]

Background: Current studies have demonstrated that disintegrin and metalloproteinase 17 (ADAM17) plays a critical role in the pathogenesis of sepsis. MicroRNA (miR)-145 is known to control immune responses as an anti-inflammatory modulatory molecule. However, a fundamental understanding of how miR-145 regulates ADAM17 and, more broadly, sepsis-induced inflammatory response remains unknown. Methods: We used western blotting and quantitative real-time PCR (qRT-PCR) to measure expression levels of ADAM17 and miR-145. Enzyme-linked immunosorbent assays (ELISA) were performed to measure cytokine production. To determine if ADAM17 is a target gene of miR-145, bioinformatics analyses and luciferase reporter assays were conducted. The impacts of ADAM17 and miR-145 on sepsis-induced inflammatory responses were accessed in vitro using human umbilical endothelial cells (HUVECs) treated with lipopolysaccharide (LPS). Sepsis-induced inflammatory response was measured in vivo using a polymicrobial septic mouse model induced by cecal ligation and puncture (CLP) with pre-injection of a miR-145 agomir. Results: In HUVECs treated with LPS, miR-145 expression was downregulated and miR-145 negatively regulated ADAM17 expression through direct binding to the ADAM17 transcript 3′-UTR. MiR-145 overexpression markedly reduced LPS-induced inflammatory cytokine production by targeting ADAM17 in HUVECs. In comparison to CLP-induced septic mice treated with a control agomir, treatment with a miR-145 agomir significantly reduced the expression of ADAM17, numerous downstream cytokines such as IL-6, TNF-α, IL-1β and MCP-1, and the endothelial injury factors ICAM-1, VCAM-1. The miR-145 agomir also alleviated acute lung and kidney injury and improved the survival rate of septic mice. Conclusions: This study showed that miR-145, by specifically targeting ADAM17, negatively regulates sepsis-induced inflammatory responses and vascular endothelial injury, and ultimately improved organ injury and survival during sepsis. The underlying mechanism for the regulation of ADAM17 expression by miR-145 and sepsis-induced inflammatory reactions may offer sepsis patients a novel therapeutic option.

The coronavirus disease 2019 (COVID-19) is still causing a wide range of infections and deaths due to the high variability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, it is necessary to establish a reliable and convenient pseudovirus-based neutralization assay to develop drug targeted variants of SARS-CoV-2. Based on the HIV-1 backbone, we generated a high titer luciferase (Luc)-expressing pseudovirus packaging system. Three dominant S mutant substitution pseudovirus were also established and identified compared to wide type in hACE2-overexpressing HEK-293T cells (293T-ACE2 cells). Compared to serine protease inhibitor camostat mesylate, the cysteine protease inhibitor E-64d could significantly block all SARS-CoV-2 mutant S pseudovirus infection in 293T-ACE2 cells. Furthermore, the neutralization ability of two antibodies targeted receptor-binding domain (RBD) of SARS-CoV-2 spike protein (S) was evaluated, which showed different inhibition dose–effect curves among four types of S pseudovirus. Overall, we developed a pseudovirus-based neutralization assay for SARS-CoV-2, which would be readily adapted to SARS-CoV-2 variants for evaluating antibodies.

Continuous consumption of fossil energy and excessive CO2 emission severely restrict human society. Sustainable carbon cycle is a promising technology to simultaneously relieve greenhouse effect and energy crisis based on electrocatalysis and photocatalysis. However, the energy conversion efficiency is confined by the poor carriers utilization and insufficient reactive sites. Single‐atom catalysts (SACs) display outstanding performance in effectively overcoming the aforementioned problems. Herein, recent advances of SACs for enhancing the efficiency, selectivity, and long‐range stability of CO2 reduction are provided. First, the characteristics of SACs have been introduced in detail to provide rational design for SACs based on the relationship between structure and performance, including type, structure, and synthesis of SACs. Then, the high performance of SACs in electrocatalytic, photocatalytic, and thermocatalytic CO2 reduction has been discussed for disclosing reaction mechanism, such as charge transfer, activation barriers, and reaction pathway. In particular, the strategies of enhancing CO2 reduction performance have been summarized to provide deep insight into designing and developing more efficient SACs. Finally, an outlook on the current challenges and perspectives of SACs for electrocatalytic, photocatalytic, and thermocatalytic CO2 reduction is proposed. This review aims to provide a systematic reference for developing SACs in advanced CO2 catalytic conversion.

Coxsackievirus A16 (CA16) belongs to the Human Enterovirus A species, which is a common pathogen causing hand, foot, and mouth disease in children. Currently, specific vaccines and drugs against CA16 are unavailable, and there is an unmet need to further understand the virus and invent effective treatment. Constructing a CA16 infectious clone with a reporter gene will greatly facilitate its virological studies. Here, we first reported the construction of a CA16 infectious clone (rCA16) whose progeny is highly replicative and virulent in suckling mice. On the basis of rCA16, we further inserted a NanoLuc (Nluc) reporter gene and made the rCA16-Nluc clone. We found that the Nluc gene in rCA16-Nluc is stable during continuous growing in Vero cells and thus allowed detection of a steady luciferase signal in rCA16-Nluc-infected Vero cells over 10 passages. Its application in antivirals characterization and high-throughput screening is exemplified by measuring IC50, CC50, and selection index of guanidine hydrochloride, ribavirin, chloroquine, and ammonium chloride against CA16. Finally, we showed that rCA16-Nluc based assay greatly simplified the CA16 neutralizing antibody tests. Thus, these two CA16 infectious clones will be robust tools for future enterovirus studies and antivirals development.

Given the high level of exposure to SARS-CoV-2, cold-chain workers are considered priority vaccination groups. To date, many studies have reported on the willingness within distinct populations to be vaccinated against COVID-19, whereas it has not been reported among cold-chain workers worldwide. To address this void, we conducted a cross-sectional survey to gather general information, COVID-19-related knowledge, attitudes, and practices (KAP), and willingness to receive a COVID-19 vaccine among cold-chain workers in Shenzhen, China. Binary logistic analyses were conducted to explore the associations between COVID-19-related KAP factors and the willingness for COVID-19 vaccination. Among 244 cold-chain workers, 76% indicated that they were willing to be vaccinated. Knowledge about SARS-CoV-2, comprehending the most effective prevention, understanding the transmission routes, and recognizing the priority vaccination groups were positively associated with willingness to be vaccinated against COVID-19. Regarding attitude factors, perceiving the social harmfulness and severity of COVID-19 were related to a higher willingness to vaccination. Participants considering themselves a priority group for COVID-19 vaccination were more likely to get vaccinated. For practice factors, attaining more knowledge and higher self-reported compliance with maintaining adequate ventilation were also positively associated with the dependent variable. Agreement on the importance of COVID-19 vaccination was the most frequent reason for accepting the COVID-19 vaccine; additionally, concerns about side effects and insufficient understanding of efficacy were the main factors contributing to vaccine refusal. Enhancing KAP levels related to COVID-19 helps promote vaccine acceptance. Health authorities should promptly implement educational activities following the updated vaccine status among cold-chain workers.

Prevalent copy number alteration is the most prominent genetic characteristic associated with ovarian cancer (OV) development, but its role in immune evasion has not been fully elucidated. In this study, we identified RAD21, a key component of the cohesin complex, as a frequently amplified oncogene that could modulate immune response in OV. Through interrogating the RAD21-regulated transcriptional program, we found that RAD21 directly interacts with YAP/TEAD4 transcriptional corepressors and recruits the NuRD complex to suppress interferon (IFN) signaling. In multiple clinical cohorts, RAD21 overexpression is inversely correlated with IFN signature gene expression in OV. We further demonstrated in murine syngeneic tumor models that RAD21 ablation potentiated anti–PD-1 efficacy with increased intratumoral CD8+ T cell effector activity. Our study identifies a RAD21–YAP/TEAD4–NuRD corepressor complex in immune modulation, and thus provides a potential target and biomarker for precision immunotherapy in OV.

Objective: Human bone marrow mesenchymal stem cell (hBMSC)-derived exosomes exhibit protective effects against inflammatory diseases. This study aimed to explore the effects of hBMSC-derived exosomes on osteoarthritis (OA) in vitro and its related mechanisms. Materials and Methods: In this experimental study, we characterised exosomes derived from hBMSCs by transmission electron microscopy, nanoparticle tracking and Western blot analysis. Cellular uptake of exosomes was observed by fluorescent microscopy. Cell viability of chondrocytes exposed to interleukin-1 beta (IL-1β) was determined by the Cell Counting Kit-8 (CCK-8). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine expression levels of genes related to apoptosis, inflammation, cartilage collagen metabolism and mitogen-activated protein kinases. Results: Fluorescence microscopy revealed that hBMSC-derived exosomes could be taken up by chondrocytes. hBMSC-derived exosomes could significantly enhance cell viability of chondrocytes in response to IL-1β treatment. RT-qPCR showed significant up-regulation of Survivin, Versican, IL-1β, IL-6, NF-κB, MMP-13, MAPK p38, JNK, ERK, Aggrecan and SOX9 expression levels by IL-1β treatment, while their mRNA expression levels decreased after coculture with exosomes. The anti-inflammatory gene TGF-β was markedly suppressed by IL-1β treatment; however, we observed its expression after co-culture with exosomes. Additionally, the pro-inflammatory genes IL-1β, IL-6, NF-κB, TNF-α and TNF-β displayed significantly elevated expression levels in the IL-1β group and reduced expression levels after co-culture with exosomes. Conclusion: hBMSC-derived exosomes may play a protective role in chondrocytes through inhibiting cell apoptosis and the inflammatory response. These results will provide a novel therapeutic strategy for OA.

ObjectiveAcoustic neuroma (AN) is a clinically common benign tumor. There are few neuropsychological investigations for AN, especially cognitive neuropsychology. Herein, the study probed into cognitive function changes in AN patients and expounded possible mechanisms through structural and functional magnetic resonance imaging (fMRI).Materials and methodsNeuropsychological tests were performed between 64 patients with AN and 67 healthy controls. Then, using resting-state fMRI, the possible mechanisms of cognitive decline in AN patients were further explored by calculating the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Furthermore, using high-resolution T1-weighted images, voxel-based morphometry (VBM) was adopted to investigate the changes in gray matter volume (GMV) and white matter volume (WMV) in AN patients.ResultsAN patients had worse cognitive performance than those in the healthy controls. Relative to the healthy individuals, the mALFF value was increased in the right caudate nucleus of the patients with left-sided AN (LAN) and the right rectus region of the patients with right-sided AN (RAN). The mReHo values of the bilateral superior frontal gyrus and middle frontal gyrus were decreased in LAN patients. Compared with healthy subjects, the GMV values were elevated in the left fusiform gyrus, parahippocampal gyrus, calcarine gyrus, and cuneus in LAN patients as well as in the right fusiform gyrus and parahippocampal gyrus in RAN patients. Meanwhile, the WMV values showed elevations in the bilateral putamen, left rectal gyrus, and thalamus in LAN patients.ConclusionCognitive dysfunction occurs in AN patients. Cognitive decline in AN patients activates functional activity in some brain regions, thereby compensating for cognition decline. Additionally, the ReHo values were reduced in the frontal lobe in LAN patients, and the connectivity was decreased, affecting the functional differentiation and integration of the brain, which may be associated with the decline in cognitive function. Lateralized brain reorganization induced by unilateral hearing loss was presented in AN patients. LAN caused a more significant interference effect on the brain while RAN patients showed more stable cerebral cortices. Altogether, responding to cognition decline in AN patients, structural reorganization occurs, and compensative increases in cognitive-related brain regions, which compensates for cognitive impairment.

Abstract Myelodysplastic syndrome with myelofibrosis (MDS-MF) has been associated with an inferior prognosis compared with MDS without MF. However, MDS-MF is not listed independently as a subtype of MDS, and its clinical and genetic characteristics remain poorly understood. We retrospectively compared 53 patients with MDS-MF (44 MF grade 1/MF1; 9 MF grade 2–3/MF2 − 3) and 31 with de novo MDS without MF (MDS). The leukemic transformation risks of both MDS-MF2 − 3 and MDS-MF1 were increased compared with the MDS group. To identify the potential mechanisms responsible for the leukemic transformation of MDS-MF, we performed single-cell sequencing for one MDS-MF2 − 3 patient before and after leukemic transformation to explore the variations in gene expression levels. In addition to upgraded expression levels of acute myeloid leukemia-related genes during leukemic transformation, expression levels of some inflammation-related genes (such as S100s, RNASE3, and CYBB) were also increased, and inflammation-related pathways were up-regulated. These results suggest that inflammation-related genes and pathways may play an important role in the leukemic transformation of MDS-MF.

Abstract Background Decades of efforts have attempted to differentiate the pluripotent stem cells (PSCs) into truly functional hematopoietic stem cells (HSCs), yet the problems of low differentiation efficiency in vitro and poor hematopoiesis reconstitution in vivo still exist, mainly attributing to the lack of solid, reproduced, or pursued differentiation system. Methods In this study, we established an in vitro differentiation system yielding in vivo hematopoietic reconstitution hematopoietic cells from mouse PSCs through a 3D induction system followed by coculture with OP9 stromal cells. The in vivo hematopoietic reconstitution potential of c-kit+ cells derived from the mouse PSCs was evaluated via m-NSG transplantation assay. Flow cytometry analysis, RNA-seq, and cell cycle analysis were used to detect the in vitro hematopoietic ability of endothelial protein C receptor (EPCR, CD201) cells generated in our induction system. Results The c-kit+ cells from 3D self-assembling peptide induction system followed by the OP9 coculture system possessed apparently superiority in terms of in vivo repopulating activity than that of 3D induction system followed by the 0.1% gelatin culture. We interestingly found that our 3D+OP9 system enriched a higher percentage of CD201+c-kit+cells that showed more similar HSC-like features such as transcriptome level and CFU formation ability than CD201-c-kit+cells, which have not been reported in the field of mouse PSCs hematopoietic differentiation. Moreover, CD201+ hematopoietic cells remained in a relatively slow cycling state, consistent with high expression levels of P57 and Ccng2. Further, we innovatively demonstrated that notch signaling pathway is responsible for in vitro CD201+ hematopoietic cell induction from mouse PSCs. Conclusions Altogether, our findings lay a foundation for improving the efficiency of hematopoietic differentiation and generating in vivo functional HSC-like cells from mouse PSCs for clinical application.

Abstract Nucleotide-binding domain and leucine-rich repeat (LRR)-containing family protein 3 (NLRP3) regulated the maturation of inflammation-related cytokines by forming NLRP3 inflammasome, which plays pivotal roles in sepsis pathogenesis. In this study, we evaluated the genetic association of NLRP3 polymorphisms with sepsis (640 patients and 769 controls) and characterized the impact of NLRP3 polymorphisms on NLRP3 expression and inflammatory responses. No significant differences were observed in genotype/allelic frequencies of NLRP3 29940G>C between sepsis cases and controls. The G allele was significantly overrepresented in patients with septic shock than those in sepsis subgroup, and the GC/GG genetypes were related to the 28-day mortality of sepsis. Lipopolysaccharide challenge to peripheral blood mononuclear cells showed a significant suppression of NLRP3 mRNA expression and release of IL-1β and TNF-α in CC compared with the GC/GG genotype category. Functional experiments with luciferase reporter vectors containing the NLRP3 3′-UTR with the 29940 G-to-C variation in HUVECs and THP-1 cells showed a potential suppressive effect of miR-146a on NLRP3 transcription in the presence of the C allele. Taken together, these results demonstrated that the 29940 G-to-C mutation within the NLRP3 3′-UTR was a gain-of-function alteration that caused the suppression of NLRP3 expression and downstream inflammatory cytokine production via binding with miR-146a, which ultimately protected patients against susceptibility to sepsis progression and poor clinical outcome.

Background: Postoperative hypoparathyroidism (hypoPT) is a common complication following thyroid surgery. However, current research findings on the risk factors for post-thyroid surgery hypoPT are not entirely consistent, and the same risk factors may have different impacts on transient and permanent hypoPT. Therefore, there is a need for a comprehensive study to summarize and explore the risk factors for both transient and permanent hypoPT after thyroid surgery. Materials and methods: Two databases (PubMed and Embase) were searched from inception to 2024. The Newcastle-Ottawa Scale was used to rate study quality. Pooled odds ratios were used to calculate the relationship of each risk factor with transient and permanent hypoPT. Subgroup analyses were conducted for hypoPT with different definition-time (6 or 12 months). Publication bias was assessed using Begg's test and Egger's test. Results: A total of 19 risk factors from the 93 studies were included in the analysis. Among them, sex and parathyroid autotransplantation were the most frequently reported risk factors. Meta-analysis demonstrated that sex (female vs. male), cN stage, central neck dissection, lateral neck dissection, extent of central neck dissection (bilateral vs. unilateral), surgery [total thyroidectomy (TT) vs. lobectomy], surgery type (TT vs. sub-TT), incidental parathyroidectomy, and pathology (cancer vs. benign) were significantly associated with transient and permanent hypoPT. Preoperative calcium and parathyroid autotransplantation were only identified as risk factors for transient hypoPT, while preoperative PTH was a protective factor. Additionally, node metastasis and parathyroid in specimen were associated with permanent hypoPT. Conclusion: The highest risk of hypoPT occurs in female thyroid cancer patients with lymph node metastasis undergoing TT combined with neck dissection. The key to preventing postoperative hypoPT lies in the selection of surgical approach and intraoperative protection. [ABSTRACT FROM AUTHOR]

Little is known about neuropsychological research on patients with acoustic neuroma (AN), especially cognitive neuropsychology. We aim to compare the cognitive function of patients with AN and healthy controls (HCs) and explore possible underlying mechanisms. Various neuropsychological assessments were performed on all participants. Tract-based spatial statistics (TBSS) was used to compare DTI metrics such as fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). Correlation analysis was analyzed between DTI metrics and cognitive scales. Compared with the HC group, the AN group performed worse in the neuropsychological evaluations, and TBSS analysis showed widespread alteration of the FA, AD, RD, and MD, which correlated with the cognitive function. These white matter tracts include minor forceps, major forceps, anterior thalamic radiation, superior longitudinal fasciculus, corticospinal tract, and right inferior fronto-occipital fasciculus. Meanwhile, we found for the first time that cognitive decline was related to the decrease of FA in minor forceps, which can be used as a neurobiological marker of cognitive impairment in patients with AN. The occurrence of cognition impairment is common in patients with AN. Including neuropsychological evaluation in the routine clinical assessment and appropriate treatment may strengthen clinical management and improve the quality of life of patients.

Abstract Background Isocitrate dehydrogenase (IDH1/2) gene mutations are the most frequently observed mutations in cartilaginous tumors. The mutant IDH causes elevation in the levels of R-enantiomer of 2-hydroxylglutarate (R-2HG). Mesenchymal stromal cells (MSCs) are reasonable precursor cell candidates of cartilaginous tumors. This study aimed to investigate the effect of oncometabolite R-2HG on MSCs. Methods Human bone marrow MSCs treated with or without R-2HG at concentrations 0.1 to 1.5 mM were used for experiments. Cell Counting Kit-8 was used to detect the proliferation of MSCs. To determine the effects of R-2HG on MSC differentiation, cells were cultured in osteogenic, chondrogenic and adipogenic medium. Specific staining approaches were performed and differentiation-related genes were quantified. Furthermore, DNA methylation status was explored by Illumina array-based arrays. Real-time PCR was applied to examine the signaling component mRNAs involved in. Results R-2HG showed no influence on the proliferation of human MSCs. R-2HG blocked osteogenic differentiation, whereas promoted adipogenic differentiation of MSCs in a dose-dependent manner. R-2HG inhibited chondrogenic differentiation of MSCs, but increased the expression of genes related to chondrocyte hypertrophy in a lower concentration (1.0 mM). Moreover, R-2HG induced a pronounced DNA hypermethylation state of MSC. R-2HG also improved promotor methylation of lineage-specific genes during osteogenic and chondrogenic differentiation. In addition, R-2HG induced hypermethylation and decreased the mRNA levels of SHH, GLI1and GLI2, indicating Sonic Hedgehog (Shh) signaling inhibition. Conclusions The oncometabolite R-2HG dysregulated the chondrogenic and osteogenic differentiation of MSCs possibly via induction of DNA hypermethylation, improving the role of R-2HG in cartilaginous tumor development.

Abstract Background Acute myeloid leukemia (AML) is a fatal hematopoietic malignancy and has a prognosis that varies with its genetic complexity. However, there has been no appropriate integrative analysis on the hierarchy of different AML subtypes. Methods Using Microwell-seq, a high-throughput single-cell mRNA sequencing platform, we analyzed the cellular hierarchy of bone marrow samples from 40 patients and 3 healthy donors. We also used single-cell single-molecule real-time (SMRT) sequencing to investigate the clonal heterogeneity of AML cells. Results From the integrative analysis of 191727 AML cells, we established a single-cell AML landscape and identified an AML progenitor cell cluster with novel AML markers. Patients with ribosomal protein high progenitor cells had a low remission rate. We deduced two types of AML with diverse clinical outcomes. We traced mitochondrial mutations in the AML landscape by combining Microwell-seq with SMRT sequencing. We propose the existence of a phenotypic “cancer attractor” that might help to define a common phenotype for AML progenitor cells. Finally, we explored the potential drug targets by making comparisons between the AML landscape and the Human Cell Landscape. Conclusions We identified a key AML progenitor cell cluster. A high ribosomal protein gene level indicates the poor prognosis. We deduced two types of AML and explored the potential drug targets. Our results suggest the existence of a cancer attractor.

BackgroundPure red cell aplasia (PRCA) is one of the important complications in major ABO-incompatible allogeneic hematopoietic stem cell transplantation (HSCT). The established pathogenic factor of PRCA is the persistence of high anti-donor isohemagglutinins. As previously verified, the conditioning regimen and donor type were the factors associated with the development of PRCA in the small-sized studies. Currently, the prevalence, risk factors, and prognosis of PRCA are still worth studying to provide evidence.MethodsWe conducted a prospective nested case-control study to determine the prevalence, donor-related factors, and the outcomes of PRCA following major ABO-incompatible transplantation. A total of 469 patients who underwent ABO-incompatible grafts were observed.ResultsNone of the patients were diagnosed with PRCA with minor or bidirectional ABO-incompatible HSCT. Thirteen of the187 patients (7%; 95% confidence interval [CI], 3.9%–11.9%) developed PRCA following major ABO-incompatible HSCT. Eleven of the 13 patients with PRCA recovered entirely. Donor type was an independent factor associated with post-HSCT PRCA (odds ratio [OR]=0.030; 95% CI, 0.003–0.321; P=0.004). The cumulative incidence rates of post-HSCT PRCA in the context of major ABO-incompatible HSCT were 0.8%, 13.1%, and 27.2% for the haploidentical donor (HID), unrelated donor, and matched related donor, respectively. No significant influence of PRCA on transplantation outcomes was observed.In conclusion, post-HSCT PRCA is a rare and less threatening complication in major ABO-incompatible HSCT. The majority of patients with PRCA could recover. Additionally, HIDs for recipients may have a low risk of post-HSCT PRCA. This trial was registered at www.chictr.org.cn (#ChiCTR2000041412).

Exploring the composition of soil organic carbon (SOC) and aggregate stability over a range of elevations is essential to evaluate the stability of SOC and the conversion of carbon source or sink of mountain ecosystems. However, information of those changes in mountain ecosystems in arid and semi-arid regions is still scarce to date. In this study, we estimated the response of SOC stability along elevation gradient (1,380–2,438 m) by combining physical protection of aggregates with chemical protection of SOC using a redundancy analysis method in the Helan Mountains, northwest China. Results showed that the dominated aggregates of Helan Mountains changed from microaggregates to macroaggregates with increasing elevation, and the mean weight diameter (MWD) in mid and high elevations (2,139–2,248 m) was significantly higher than that in low elevations (1,380–1,650 m). Solid-state 13C NMR spectra showed that O-alkyl C was the main chemical composition of SOC in the different elevations. Regression analysis indicated that with the increase of elevation, the proportion of aromatic C and aromaticity gradually increased, peaked at the mid elevation and subsequently decreased. These findings indicated that the soil structure and chemical composition of SOC are more stable in the mid elevation. Macroaggregates were positively correlated with O-alkyl C and aromatic C, while silt and clay were positively correlated with alkyl C, indicative of a lower decomposition rate of macroaggregates. The RDA analysis confirmed that aggregate stability were significant associated with SOC content and chemical composition such as O-alkyl C, indicating that the soil labile carbon pool was most related to affect aggregate stability. Our findings suggest that the Helan Mountains had a better soil structure and a more stable SOC chemical composition at mid elevation ranges. The soil structure at low elevations is sensitive to environment change; therefore, a reduction in anthropogenic disturbance is suggested for improved sustainability of the ecosystem.

ObjectiveTo evaluate the efficacy and safety of standard or low-dose chemotherapy followed by HLA-mismatched allogeneic T-cell infusion (allo-TLI) for the treatment of elderly patients with acute myeloid leukemia (AML) and patients with intermediate-2 to high-risk myelodysplastic syndrome (MDS).MethodsWe carried out a prospective, multicenter, single-arm clinical trial. Totally of 25 patients were enrolled, including 17 AML patients and 8 MDS patients. Each patient received four courses of non-ablative chemotherapy, with HLA-mismatched donor CD3+ allo-TLI 24 h after each course. AML patients received chemotherapy with decitabine, idarubicin, and cytarabine, and MDS patients received decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor.ResultsA total of 79 procedures were performed. The overall response rates of the AML and MDS patients were 94% and 75% and the 1-year overall survival rates were 88% (61–97%) and 60% (13–88%), respectively. The overall 60-day treatment-related mortality was 8%. Compared with a historical control cohort that received idarubicin plus cytarabine (3 + 7), the study group showed significantly better overall response (94% vs. 50%, P=0.002) and overall survival rates (the 1-year OS rate was 88% vs. 27%, P=0.014). Post-TLI cytokine-release syndrome (CRS) occurred after 79% of allo-TLI operations, and 96% of CRS reactions were grade 1.ConclusionElderly AML patients and intermediate-2 to high-risk MDS patients are usually insensitive to or cannot tolerate regular chemotherapies, and may not have the opportunity to undergo allogeneic stem cell transplantation. Our study showed that non-ablative chemotherapy followed by HLA-mismatched allo-TLI is safe and effective, and may thus be used as a first-line treatment for these patients.Clinical Trial Registrationhttps://www.chictr.org.cn/showproj.aspx?proj=20112.

Bronchiolitis obliterans syndrome (BOS) is a life-threatening pulmonary manifestation of chronic graft versus host disease (cGVHD) post-allogeneic hematopoietic stem cell transplantation (HSCT), without clear standard of care. This study included 30 patients undergoing an allogeneic HSCT for a hematological malignancy and the outcomes with post-HSCT BOS treated with ruxolitinib as a salvage treatment were reviewed. After a median duration of ruxolitinib therapy of 9.25 (1.5–27) months, the best overall response (BOR) rate was 66.7%: three patients (10.0%) achieved complete remission, and 17 (56.7%) achieved partial remission. The median time from initiation of ruxolitinib to achieve the best responses was 3 months. Since initiating ruxolitinib, forced expiratory volume in 1 s of predicted (FEV1%pred) slightly increased after 3 and 6 months compared with measurements before ruxolitinib in responders. Only FEV1%pred mild decline before ruxolitinib with a ratio ≤15% was an independent predictor to achieve a response to ruxolitinib. Eleven patients (36.7%) had severe pulmonary infection of ≥3 grade. Following a median follow-up of 318 days after ruxolitinib, the 2-years incidence of nonrelapse mortality and 2-years overall survival rate after ruxolitinib among patients with BOS was 25.1 and 62.6%, respectively. Ruxolitinib is a promising treatment option to improve the prognosis of post-HSCT BOS.