Single-cell landscape reveals the immune heterogeneity of bone marrow involvement in peripheral T-cell lymphoma.

The prognosis of patients with peripheral T-cell lymphoma (PTCL) depends on bone marrow involvement (BMI). The bone marrow (BM) tumor microenvironment in PTCL remains unclear. We performed single-cell RNA sequencing (scRNA-seq) on 11 fresh BM samples from patients with BMI to reveal the associations of immune landscape and genetic variations with the prognosis of PTCL patients. Compared with PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL) had a higher number of T cells, lower number of lymphocytes, and greater inflammation. Immune heterogeneity in AITL is associated with prognosis. In particular, specific T-cell receptor (TCR) T cells are enriched in patients with good response to anti-CD30 therapy. We observed RhoA mutation-associated neoantigens. Chidamide-treated patients had a higher number of CD4+ regulatory cells and a better treatment response compared with other patients. In the nonresponder group, T-cell enrichment progressed to secondary B-cell enrichment and subsequently diffuse large B-cell lymphoma. Moreover, AITL patients with lymphoma-associated hemophagocytic syndrome had more T follicular helper (Tfh) cells with copy number variations in CHR5. To our knowledge, this study is the first to reveal the single-cell landscape of BM microenvironment heterogeneity in PTCL patients with BMI. scRNA-seq can be used to investigate the immune heterogeneity and genetic variations in AITL associated with prognosis.

A new In Situ Oxidized 2D Layered MnBi2Te4 Cathode for High-Performance Aqueous Zinc-Ion Battery.

Recently, aqueous zinc ion batteries (AZIBs) with the superior theoretical capacity, high safety, low prices, and environmental protection, have emerged as a contender for advanced energy storage. However, challenges related to cathode materials, such as dissolution, instability, and structural collapse, have hindered the progress of AZIBs. Here, a novel AZIB is constructed using an oxidized 2D layered MnBi2Te4 cathode for the first time. The oxidized MnBi2Te4 cathode with large interlayer spacing and low energy barrier for zinc ion diffusion at 240 °C, exhibited impressive characteristics, including a high reversibility capacity of 393.1 mAh g-1 (0.4 A g-1), outstanding rate performance, and long cycle stability. Moreover, the corresponding aqueous button cell also exhibits excellent electrochemical performance. To demonstrate the application in practice in the realm of flexible wearable electronics, a quasi-solid-state micro ZIB (MZIB) is constructed and shows excellent flexibility and high-temperature stability (the capacity does not significantly degrade when the temperature reaches 100 °C and the bending angle exceeds 150°). This research offers effective tactics for creating high-performance cathode materials for AZIBs.

Prenatal Diagnosis of Cerebellar Cortical Dysplasia: Case Report.

This was a study of 12 cerebellar cortical dysplasias (CCDs) fetuses, these cases were characterized by a disorder of cerebellar fissures. Historically, CCD diagnosis was primarily performed using postnatal imaging. Unique to this study was the case series of CCD for prenatal diagnosis using prenatal ultrasound, as well as we found that AXIN1 and FOXC1 mutations may be related to CCD.

Dynamic Traffic Data in Machine-Learning Air Quality Mapping Improves Environmental Justice Assessment.

Air pollution poses a critical public health threat around many megacities but in an uneven manner. Conventional models are limited to depict the highly spatial- and time-varying patterns of ambient pollutant exposures at the community scale for megacities. Here, we developed a machine-learning approach that leverages the dynamic traffic profiles to continuously estimate community-level year-long air pollutant concentrations in Los Angeles, U.S. We found the introduction of real-world dynamic traffic data significantly improved the spatial fidelity of nitrogen dioxide (NO2), maximum daily 8-h average ozone (MDA8 O3), and fine particulate matter (PM2.5) simulations by 47%, 4%, and 15%, respectively. We successfully captured PM2.5 levels exceeding limits due to heavy traffic activities and providing an "out-of-limit map" tool to identify exposure disparities within highly polluted communities. In contrast, the model without real-world dynamic traffic data lacks the ability to capture the traffic-induced exposure disparities and significantly underestimate residents' exposure to PM2.5. The underestimations are more severe for disadvantaged communities such as black and low-income groups, showing the significance of incorporating real-time traffic data in exposure disparity assessment.

Regulatory Insights for On-Board Monitoring of Vehicular NOx Emission Compliance.

Nitrogen oxide (NOx) emissions from heavy-duty diesel vehicles (HDDVs) have adverse effects on human health and the environment. On-board monitoring (OBM), which can continuously collect vehicle performance and NOx emissions throughout the operation lifespan, is recognized as the core technology for future vehicle in-use compliance, but its large-scale application has not been reported. Here, we utilized OBM data from 22,520 HDDVs in China to evaluate their real-world NOx emissions. Our findings showed that China VI HDDVs had a 73% NOx emission reduction compared with China V vehicles, but a considerable proportion still faced a significant risk of higher NOx emissions than the corresponding limits. The unsatisfactory efficiency of the emission treatment system under disadvantageous driving conditions (e.g., low speed or ambient temperature) resulted in the incompliance of NOx emissions, especially for utility vehicles (sanitation/garbage trucks). Furthermore, the observed intertrip and seasonal variability of NOx emissions demonstrated the need for a long-term continuous monitoring protocol instead of instantaneous evaluation for the OBM. With both functions of emission monitoring and malfunction diagnostics, OBM has the potential to accurately verify the in-use compliance status of large-scale HDDVs and discern the responsibility of high-emitting activities from manufacturers, vehicle operators, and driving conditions.

Integrated Benefits of Synergistically Reducing Air Pollutants and Carbon Dioxide in China.

China's advancements in addressing air pollution and reducing CO2 emissions offer valuable lessons for collaborative strategies to achieve diverse environmental objectives. Previous studies have assessed the mutual benefits of climate policies and air pollution control measures on one another, lacking an integrated assessment of the benefits of synergistic control attributed to refined measures. Here, we comprehensively used coupled emission inventory and response models to evaluate the integrated benefits and synergy degrees of various measures in reducing air pollutants and CO2 in China during 2013-2021. Results indicated that the implemented measures yielded integrated benefits value at 6.7 (2.4-12.6) trillion Chinese Yuan. The top five contributors, accounting for 55%, included promoting non-thermal power, implementing end-of-pipe control technologies in power plants and iron and steel industry, replacing residential scattered coal, and saving building energy. Measures demonstrating high synergies and integrated benefits per unit of reduction (e.g., green traffic promotion) yielded low benefits mainly due to their low application, which are expected to gain greater implementation and prioritization in the future. Our findings provide insights into the effectiveness and limitations of strategies aimed at joint control. By ranking these measures based on their benefits and synergy, we offer valuable guidance for policy development in China and other nations with similar needs.

FOSL1 regulates hyperproliferation and NLRP3-mediated inflammation of psoriatic keratinocytes through the NF-kB signaling via transcriptionally activating TRAF3.

Psoriasis is a common and immune-mediated skin disease related to keratinocytes hyperproliferation and inflammation. Fos-like antigen-1 (FOSL1) is an important transcription factor involved in various diseases. FOSL1 has been reported to be differentially expressed in psoriasis. However, the roles and mechanism of FOSL1 in psoriasis progression remain largely unknown. FOSL1 is an upregulated transcription factor in psoriasis and increased in M5-treated HaCaT cells. FOSL1 had a diagnostic value in psoriasis, and positively associated with PASI score, TNF-α and IL-6 levels in psoriasis patients. FOSL1 silencing attenuated M5-induced HaCaT cell hyperproliferation through decreasing cell viability and proliferative ability and increasing cell apoptosis. FOSL1 knockdown mitigated M5-induced NLRP3 inflammasome activation and it-mediated inflammatory cytokine (IL-6, IL-8 and CCL17) expression. TRAF3 expression was increased in psoriasis patients and M5-treated HaCaT cells. FOSL1 transcriptionally activating TRAF3 in HaCaT cells. TRAF3 overexpression reversed the suppressive effects of FOSL1 silencing on M5-induced hyperproliferation and NLRP3-mediated inflammation. FOSL1 knockdown attenuated M5-induced NF-κB signaling activation by reducing TRAF3. Activation of NF-κB signaling reversed the effects of FOSL1 knockdown on hyperproliferation and inflammation in M5-treated cells. FOSL1 silencing prevented M5-induced hyperproliferation and NLRP3-mediated inflammation of keratinocytes by inhibiting TRAF3-mediated NF-κB activity, indicating FOSL1 might act as a therapeutic target of psoriasis.

Health benefits of vehicle electrification through air pollution in Shanghai, China.

Vehicle electrification has been recognized for its potential to reduce emissions of air pollutants and greenhouse gases in China. Several studies have estimated how national-level policies of electric vehicle (EV) adoption might bring very large environmental and public health benefits from improved air quality to China. However, large-scale adoption is very costly, some regions derive more benefits from large-scale EV adoption than others, and the benefits of replacing internal combustion engines in specific cities are less known. Therefore, it is important for policymakers to design incentives based on regional characteristics - especially for megacities like Shanghai - which typically suffer from worse air quality and where a larger population is exposed to emissions from vehicles. Over the past five years, Shanghai has offered substantial personal subsidies for passenger EVs to accelerate its electrification efforts. Still, it remains uncertain whether EV benefits justify the strength of incentives. The purpose of our study is to evaluate the health and climate benefits of replacing light-duty gasoline vehicles (ICEVs) with battery EVs in the city of Shanghai. We assess health impacts due to ICEV emissions of primary fine particulate matter, NOx, and volatile organic compounds, and to powerplant emissions of NOx and SO2 due to EV charging. We incorporate climate benefits from reduced greenhouse gas emissions based on existing research. We find that the benefit of replacing the average ICEV with an EV in Shanghai is US$6400 (2400-14,700), with health impacts of EVs about 20 times lower than the average ICEV. Larger benefits ensue if older ICEVs are replaced, but replacing newer China ICEVs also achieves positive health benefits. As Shanghai plans to stop providing personal subsidies for EV purchases in 2024, our results show that EVs achieve public health and climate benefits and can help inform policymaking strategies in Shanghai and other megacities.

Impact of battery electric vehicle usage on air quality in three Chinese first-tier cities.

China, the world leader in automobile production and sales, confronts the challenge of transportation emissions, which account for roughly 10% of its total carbon emissions. This study, utilizing real-world vehicle data from three major Chinese cities, assesses the impact of Battery Electric Vehicles (BEVs) on air quality. Our analysis reveals that BEVs, when replacing gasoline vehicles in their operational phase, significantly reduce emissions, with reductions ranging from 8.72 to 85.71 kg of CO2 per vehicle monthly. The average monthly reduction rate is 9.47%, though this effect is less pronounced during winter. Advanced BEVs, characterized by higher efficiency and newer technology, exhibit greater emission reduction benefits. While private BEVs generally contribute positively to environmental outcomes, taxi BEVs, due to their intensive usage patterns, show less environmental advantage and may sometimes worsen air quality. Looking ahead, we project substantial emission reductions from the replacement of gasoline vehicles with electric alternatives over the next decade. Policymakers are urged to adopt proactive measures, focusing on promoting medium to large electric vehicles and fostering the use of private and ride-hailing electric vehicles.

Impacts of ethanol blended fuels and cold temperature on VOC emissions from gasoline vehicles in China.

The Chinese central government has initiated pilot projects to promote the adoption of gasoline containing 10%v ethanol (E10). Vehicle emissions using ethanol blended fuels require investigation to estimate the environmental impacts of the initiative. Five fuel formulations were created using two blending methods (splash blending and match blending) to evaluate the impacts of formulations on speciated volatile organic compounds (VOCs) from exhaust emissions. Seven in-use vehicles covering China 4 to China 6 emission standards were recruited. Vehicle tests were conducted using the Worldwide Harmonized Test Cycle (WLTC) in a temperature-controlled chamber at 23 °C and -7 °C. Splash blended E10 fuels led to significant reductions in VOC emissions by 12%-75%. E10 fuels had a better performance of reducing VOC emissions in older model vehicles than in newer model vehicles. These results suggested that E10 fuel could be an option to mitigate the VOC emissions. Although replacing methyl tert-butyl ether (MTBE) with ethanol in regular gasoline had no significant effects on VOC emissions, the replacement led to lower aromatic emissions by 40%-60%. Alkanes and aromatics dominated approximately 90% of VOC emissions for all vehicle-fuel combinations. Cold temperature increased VOC emissions significantly, by 3-26 folds for all vehicle/fuel combinations at -7 °C. Aromatic emissions were increased by cold temperature, from 2 to 26 mg/km at 23 °C to 33-238 mg/km at -7 °C. OVOC emissions were not significantly affected by E10 fuel or cold temperature. The ozone formation potential (OFP) and secondary organic aerosol formation potential (SOAFP) of splash blended E10 fuels decreased by up to 76% and 81%, respectively, compared with those of E0 fuels. The results are useful to update VOC emission profiles of Chinese vehicles using ethanol blended gasoline and under low-temperature conditions.

Corilagin relieves atherosclerosis via the toll-like receptor 4 signaling pathway in vascular smooth muscle cells.

INTRODUCTION: Corilagin possesses a diverse range of pharmacologic bioactivities. However, the specific protective effects and mechanisms of action of corilagin in the context of atherosclerosis remain unclear. In this study, we investigated the impact of corilagin on the toll-like receptor (TLR)4 signaling pathway in a mouse vascular smooth muscle cell line (MOVAS) stimulated by oxidized low-density lipoprotein (ox-LDL). Additionally, we examined the effects of corilagin in Sprague-Dawley rats experiencing atherosclerosis. METHODS: The cytotoxicity of corilagin was assessed using the CCK8 assay. MOVAS cells, pre-incubated with ox-LDL, underwent treatment with varying concentrations of corilagin. TLR4 expression was modulated by either downregulation through small interfering (si)RNA or upregulation via lentivirus transfection. Molecular expression within the TLR4 signaling pathway was analyzed using real-time polymerase chain reaction (PCR) and Western blotting. The proliferation capacity of MOVAS cells was determined through cell counting. In a rat model, atherosclerosis was induced in femoral arteries using an improved guidewire injury method, and TLR4 expression in plaque areas was assessed using immunofluorescence. Pathological changes were examined through hematoxylin and eosin staining, as well as Oil-Red-O staining. RESULTS: Corilagin demonstrated inhibitory effects on the TLR4 signaling pathway in MOVAS cells pre-stimulated with ox-LDL, consequently impeding the proliferative impact of ox-LDL. The modulation of TLR4 expression, either through downregulation or upregulation, similarly influenced the expression of downstream molecules. In an in vivo context, corilagin exhibited the ability to suppress TLR4 and MyD88 expression in the plaque lesion areas of rat femoral arteries, thereby alleviating the formation of atherosclerotic plaques. CONCLUSION: Corilagin can inhibit the TLR4 signaling pathway in VSMCs, possibly by downregulating TLR4 expression and, consequently, relieving atherosclerosis.

Characterization of on-road nitrogen oxides and black carbon emissions from high emitters of heavy-duty diesel vehicles in China.

Heavy-duty diesel vehicles (HDDVs) significantly contribute to atmospheric nitrogen oxides (NOX) and black carbon (BC), with high emitters within the HDDV fleet impacting the total emissions. However, emission patterns and contributions of high emitters are rarely explored from a fleet-perspective. We investigated NOX and BC emission factors (EFs) from 1925 HDDVs in Shenzhen by the plume-chasing method, and found that the fleet-average EFs decreased with stricter emission standards. Unexpectedly, the average NOX EF for the China IV fleet was comparable with that for the China III fleet due to possible ineffective aftertreatment in high-emitter sectors of China IV HDDVs. Decreasing trend in average NOX EF since 2017 reflected the effective emission controls by the implementation of China V standard. Besides, semi-trailer tractors exhibited a higher incidence of NOX over-emissions, whereas BC high emitters were more pronounced in box trucks. Total NOX and BC emissions from HDDVs in Shenzhen were revisited, reaching 54.0 and 1.1 Gg·yr-1, with updated NOX EF correcting a 26.2 % underestimation in national guidelines. Notably, eliminating high emitters yields greater emission reduction benefits than merely retiring old HDDVs, with BC reduction outpacing NOX. This study provides new insights into the implementation of targeted emission reduction measures for HDDVs.

Response of organic aerosol in Beijing to emission reductions during the XXIV Olympic Winter Games.

Organic aerosol (OA) serves as a crucial component of fine particulate matter. However, the response of OA to changes in anthropogenic emissions remains unclear due to its complexity. The XXIV Olympic Winter Games (OWG) provided real atmospheric experimental conditions on studying the response of OA to substantial emission reductions in winter. Here, we explored the sources and variations of OA based on the observation of aerosol mass spectrometer (AMS) combined with positive matrix factorization (PMF) analysis in urban Beijing during the 2022 Olympic Winter Games. The influences of meteorological conditions on OA concentrations were corrected by CO and verified by deweathered model. The CO-normalized primary OA (POA) concentrations from traffic, cooking, coal and biomass burning during the OWG decreased by 39.8 %, 23.2 % and 65.0 %, respectively. Measures controlling coal and biomass burning were most effective in reducing POA during the OWG. For the CO-normalized concentration of secondary OA (SOA), aqueous-phase related oxygenated OA decreased by 51.8 % due to the lower relative humidity and emission reduction in precursors, while the less oxidized­oxygenated OA even slightly increased as the enhanced atmospheric oxidation processes may partially offset the efficacy of emission control. Therefore, more targeted reduction of organic precursors shall be enhanced to lower atmospheric oxidation capacity and mitigate SOA pollution.

Unpacking the factors contributing to changes in PM2.5-associated mortality in China from 2013 to 2019.

From 2013 to 2019, a series of air pollution control actions significantly reduced PM2.5 pollution in China. Control actions included changes in activity levels, structural adjustment (SA) policy, energy and material saving (EMS) policy, and end-of-pipe (EOP) control in several sources, which have not been systematically studied in previous studies. Here, we integrate an emission inventory, a chemical transport model, a health impact assessment model, and a scenario analysis to quantify the contribution of each control action across a range of major emission sources to the changes in PM2.5 concentrations and associated mortality in China from 2013 to 2019. Assuming equal toxicity of PM2.5 from all the sources, we estimate that PM2.5-related mortality decreased from 2.52 (95 % confidence interval, 2.13-2.88) to 1.94 (1.62-2.24) million deaths. Anthropogenic emission reductions and declining baseline incidence rates significantly contributed to health benefits, but population aging partially offset their impact. Among the major sources, controls on power plants and industrial boilers were responsible for the highest reduction in PM2.5-related mortality (∼80 %), followed by industrial processes (∼40 %), residential combustion (∼40 %), and transportation (∼30 %). However, considering the potentially higher relative risks of power plant PM2.5, the adverse effects avoided by their control could be ∼2.4 times the current estimation. Our power plant sensitivity analyses indicate that future estimates of source-specific PM2.5 health effects should incorporate variations in individual source PM2.5 effect coefficients when available. As for the control actions, while activity levels increased for most sources, SA policy significantly reduced the emissions in residential combustion and industrial boilers, and EOP control dominated the contribution in health benefits in most sources except residential combustion. Considering the emission reduction potential by source and control actions in 2019, our results suggest that promoting clean energy in residential combustion and enforcing more stringent EOP control in the iron and steel industry should be prioritized in the future.

Drug recommendation for optimization on treatment outcome for MDR/RR-TB based on a multi-center, large scale, retrospective cohort study in China.

OBJECTIVE: With the change in drug-resistant pattern, MDR/RR-TB was faced with underlying changes in regimens. A multi-center, large-scale, retrospective study performed aims to provide a recommendation of drug selection on optimization of outcome for the patients. METHOD: The study was conducted in six TB-specialized hospitals in China. Patients were included from 2018-2021 and followed up throughout the treatment. Using a multivarariable and propensity score-matched logistic regression analysis, we evaluated associations between outcomes and drug use, as well as clinical characteritics. RESULTS: Of 3112 patients, 74.29% had treatment sucess, 14.52% lost to follow-up, 9.67% failure, and 1.51% died. Treatment success was positively associated with Bedaquiline(Bdq), Linezolid(Lzd), and Cycloserin(Cs). Capreomycin(Cm) increased the risk of unfavorable outcomes. other drugs such as Amikacin(Amk) and clofazimine had no significant effect on outcomes. If isolates were susceptible to fluoroquinolones(FQs), FQs could decrease the risk of unfavorable outcomes. CONCLUSIONS: The recommendation order for the treatment of MDR/RR-TB is Bdq, Lzd, and Cs. FQs were decreased in use intensity. Injection drugs, whether Amk or Cm, are not recommended.

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.

An ultra low-input method for global RNA structure probing uncovers Regnase-1-mediated regulation in macrophages.

To enable diverse functions and precise regulation, an RNA sequence often folds into complex yet distinct structures in different cellular states. Probing RNA in its native environment is essential to uncovering RNA structures of biological contexts. However, current methods generally require large amounts of input RNA and are challenging for physiologically relevant use. Here, we report smartSHAPE, a new RNA structure probing method that requires very low amounts of RNA input due to the largely reduced artefact of probing signals and increased efficiency of library construction. Using smartSHAPE, we showcased the profiling of the RNA structure landscape of mouse intestinal macrophages upon inflammation, and provided evidence that RNA conformational changes regulate immune responses. These results demonstrate that smartSHAPE can greatly expand the scope of RNA structure-based investigations in practical biological systems, and also provide a research paradigm for the study of post-transcriptional regulation.