PAF remodels the DREAM complex to bypass cell quiescence and promote lung tumorigenesis.

The DREAM complex orchestrates cell quiescence and the cell cycle. However, how the DREAM complex is deregulated in cancer remains elusive. Here, we report that PAF (PCLAF/KIAA0101) drives cell quiescence exit to promote lung tumorigenesis by remodeling the DREAM complex. PAF is highly expressed in lung adenocarcinoma (LUAD) and is associated with poor prognosis. Importantly, Paf knockout markedly suppressed LUAD development in mouse models. PAF depletion induced LUAD cell quiescence and growth arrest. PAF is required for the global expression of cell-cycle genes controlled by the repressive DREAM complex. Mechanistically, PAF inhibits DREAM complex formation by binding to RBBP4, a core DREAM subunit, leading to transactivation of DREAM target genes. Furthermore, pharmacological mimicking of PAF-depleted transcriptomes inhibited LUAD tumor growth. Our results unveil how the PAF-remodeled DREAM complex bypasses cell quiescence to promote lung tumorigenesis and suggest that the PAF-DREAM axis may be a therapeutic vulnerability in lung cancer.

Structure-based classification predicts drug response in EGFR-mutant NSCLC.

Epidermal growth factor receptor (EGFR) mutations typically occur in exons 18-21 and are established driver mutations in non-small cell lung cancer (NSCLC)1-3. Targeted therapies are approved for patients with 'classical' mutations and a small number of other mutations4-6. However, effective therapies have not been identified for additional EGFR mutations. Furthermore, the frequency and effects of atypical EGFR mutations on drug sensitivity are unknown1,3,7-10. Here we characterize the mutational landscape in 16,715 patients with EGFR-mutant NSCLC, and establish the structure-function relationship of EGFR mutations on drug sensitivity. We found that EGFR mutations can be separated into four distinct subgroups on the basis of sensitivity and structural changes that retrospectively predict patient outcomes following treatment with EGFR inhibitors better than traditional exon-based groups. Together, these data delineate a structure-based approach for defining functional groups of EGFR mutations that can effectively guide treatment and clinical trial choices for patients with EGFR-mutant NSCLC and suggest that a structure-function-based approach may improve the prediction of drug sensitivity to targeted therapies in oncogenes with diverse mutations.

Cyclic Ether Derived Stable Solid Electrolyte Interphase on Bismuth Anodes for Ultrahigh-Rate Sodium-Ion Storage.

The bismuth anode has garnered significant attention due to its high theoretical Na-storage capacity (386 mAh g-1). There have been numerous research reports on the stable solid electrolyte interphase (SEI) facilitated by electrolytes utilizing ether solvents. In this contribution, cyclic tetrahydrofuran (THF) and 2-methyltetrahydrofuran (MeTHF) ethers are employed as solvents to investigate the sodium-ion storage properties of bismuth anodes. A series of detailed characterizations are utilized to analyze the impact of electrolyte solvation structure and SEI chemical composition on the kinetics of sodium-ion storage. The findings reveal that bismuth anodes in both THF and MeTHF-based electrolytes exhibit exceptional rate performance at low current densities, but in THF-based electrolytes, the reversible capacity is higher at high current densities (316.7 mAh g-1 in THF compared to 9.7 mAh g-1 in MeTHF at 50 A g-1). This stark difference is attributed to the formation of an inorganic-rich, thin, and uniform SEI derived from THF-based electrolyte. Although the SEI derived from MeTHF-based electrolyte also consists predominantly of inorganic components, it is thicker and contains more organic species compared to the THF-derived SEI, impeding charge transfer and ion diffusion. This study offers valuable insights into the utilization of cyclic ether electrolytes for Na-ion batteries.

Model-based dosing optimization and therapeutic drug monitoring practices of teicoplanin in patients with complicated or non-complicated methicillin-resistant staphylococcus aureus infection.

AIMS: This study aims to establish a population pharmacokinetic (PK) model of teicoplanin in Chinese adult patients to evaluate the dosing regimen in the label sheet and optimize it. METHODS: Nonlinear mixed-effects modelling was used to estimate PK parameters. Monte Carlo simulations were used to evaluate the attainment of various dosing regimens in achieving the target trough concentrations in patients with normal or decreased renal function. RESULTS: A total of 115 patients were enrolled in this retrospective study. Creatinine clearance (CrCL) and albumin (ALB) were identified as covariates on the clearance of teicoplanin. For the treatment of non-complicated methicillin-resistant Staphylococcus aureus (MRSA) infections in patients with normal renal function and serum ALB concentration, the recommended dosing regimen was 600 mg q12h with five administrations as the loading dose followed by 600 mg qd as the maintenance dose; for the treatment of serious and/or complicated MRSA infections, the recommended dosing regimen was 800 mg q12h with five administrations as the loading dose followed by 800 mg qd as the maintenance dose. It is worth noting that both the loading and maintenance doses ought to be modified based on the patient's renal function and serum ALB concentration. In addition, trough concentrations of teicoplanin were significantly increased every other week. CONCLUSIONS: Both loading dosing and maintenance dosing regimens were recommended to be adjusted according to patient's renal function and serum ALB concentration. In addition, it is necessary to perform follow-up therapeutic drug monitoring of teicoplanin at least once every week.

Methylmercury exposure and risk of wintering migratory birds in the Poyang Lake basin, China.

Mercury (Hg), especially methylmercury (MeHg), is a pervasive contaminant that poses significant risks to birds occupying high trophic levels. However, we have little knowledge about the mercury exposure and its risks for birds in Poyang Lake basin, China. Therefore, during 2020-2021, we investigated MeHg concentrations in breast feathers of wintering migratory birds (n=430 from 43 species belonging to 9 orders) in Poyang Lake Nanji Wetland and Jiangxi Nanfengmian National Nature Reserve, China. MeHg concentrations in breast feathers varied greatly by species, foraging guilds and taxonomic orders, among which the highest concentration was detected in great egret (8849 ± 5975 ng g-1 dw). Comparing with studies worldwide, high MeHg concentrations in feathers of Ardeidae from Pelecaniformes were found in this area. Moreover, herons migrating between northern and southern China had lower MeHg concentration than residents in southern China related to habitat Hg. Considering the applicability and sensitivity of the equations for the transformation of MeHg concentrations in feathers to blood-equivalent total Hg (THg) values, method CJ that the equation based on songbirds was used for the transformation of the songbirds and the equation based on seabirds for the others performed better than other three for risk assessment of bird Hg in this study. 23.1% of birds from Poyang Lake were at risk of Hg exposure based on the method CJ. Carnivorous birds from Pelecaniformes had the highest risk levels, with 37.2% categorized as no risk (≤ 200 ng g-1 ww), 48.9% as low risk (200∼1000 ng g-1 ww), 11.1% as moderate risk (1000∼3000 ng g-1 ww), 1.1% as high risk (3000∼4000 ng g-1 ww), and 1.7% as severe risk (> 4000 ng g-1 ww). These risks suggest long-term monitoring and further advanced studies about freshwater waterbirds Hg exposure is necessary.

Structure and Interface Engineering of Ultrahigh-Rate 3D Bismuth Anodes for Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have attracted tremendous attention as promising low-cost energy storage devices in future grid-scale energy management applications. Bismuth is a promising anode for SIBs due to its high theoretical capacity (386 mAh g-1 ). Nevertheless, the huge volume variation of Bi anode during (de)sodiation processes can cause the pulverization of Bi particulates and rupture of solid electrolyte interphase (SEI), resulting in quick capacity decay. It is demonstrated that rigid carbon framework and robust SEI are two essentials for stable Bi anodes. A lignin-derived carbonlayer wrapped tightly around the bismuth nanospheres provides a stable conductive pathway, while the delicate selection of linear and cyclic ether-based electrolytes enable robust and stable SEI films. These two merits enable the long-term cycling process of the LC-Bi anode. The LC-Bi composite delivers outstanding sodium-ion storage performance with an ultra-long cycle life of 10 000 cycles at a high current density of 5 A g-1 and an excellent rate capability of 94% capacity retention at an ultrahigh current density of 100 A g-1 . Herein, the underlying origins of performance improvement of Bi anode are elucidated, which provides a rational design strategy for Bi anodes in practical SIBs.

A simple and available measurement of onco-sEV dsDNA to protein ratio as a potential tumor marker.

BACKGROUND: Small extracellular vesicles (sEVs) have great potential as new biomarkers in liquid biopsy. However, due to the limitations of sEVs extraction and component analysis procedures, further clinical applications of sEVs are hampered. Carcinoembryonic antigen (CEA) is a commonly used broad-spectrum tumor marker that is strongly expressed in a variety of malignancies. RESULTS: In this study, CEA+ sEVs were directly separated from serum using immunomagnetic beads, and the nucleic acid to protein ultraviolet absorption ratio (NPr) of CEA+ sEVs was determined. It was found that the NPr of CEA+ sEVs in tumor group was higher than that of healthy group. We further analyzed the sEV-derived nucleic acid components using fluorescent staining and found that the concentration ratio of double-stranded DNA to protein (dsDPr) in CEA+ sEVs was also significantly different between the two groups, with a sensitivity of 100% and a specificity of 41.67% for the diagnosis of pan-cancer. The AUC of dsDPr combined with NPr was 0.87 and the ACU of dsDPr combined with CA242 could reach 0.94, showing good diagnostic performance for pan-cancer. CONCLUSIONS: This study demonstrates that the dsDPr of CEA+ sEVs can effectively distinguish sEVs derived from tumor patients and healthy individuals, which can be employed as a simple and cost-effective non-invasive screening technology to assist tumor diagnosis.

Successful osimertinib rechallenge after severe thrombocytopenia caused by osimertinib combined with sitagliptin: a case report.

Osimertinib is recommended as the first-line treatment of advanced non-small cell lung cancer (NSCLC) in adults. The most commonly reported adverse events for osimertinib are skin effects, diarrhea, nausea, decreased appetite, fatigue, paronychia, and stomatitis. Severe thrombocytopenia is rarely reported. We present a case of severe thrombocytopenia in a 70-year-old NSCLC patient caused by osimertinib combined with sitagliptin. After remission of thrombocytopenia, the patient was well tolerated with osimertinib re-administration in the absence of sitagliptin. We speculated that declined platelet count might be related to the interaction between osimertinib and sitagliptin by acting with a synergistic effect on platelets. Osimertinib rechallenge can be considered after discontinuing drugs that may contribute to platelet decline if possible, and making a careful assessment of complete blood count and risk of bleeding.

Evolution of Ozone Pollution in China: What Track Will It Follow?

Increasing surface ozone (O3) concentrations has emerged as a key air pollution problem in many urban regions worldwide in the last decade. A longstanding major issue in tackling ozone pollution is the identification of the O3 formation regime and its sensitivity to precursor emissions. In this work, we propose a new transformed empirical kinetic modeling approach (EKMA) to diagnose the O3 formation regime using regulatory O3 and NO2 observation datasets, which are easily accessible. We demonstrate that mapping of monitored O3 and NO2 data on the modeled regional O3-NO2 relationship diagram can illustrate the ozone formation regime and historical evolution of O3 precursors of the region. By applying this new approach, we show that for most urban regions of China, the O3 formation is currently associated with a volatile organic compound (VOC)-limited regime, which is located within the zone of daytime-produced O3 (DPO3) to an 8h-NO2 concentration ratio below 8.3 ([DPO3]/[8h-NO2] ≤ 8.3). The ozone production and controlling effects of VOCs and NOx in different cities of China were compared according to their historical O3-NO2 evolution routes. The approach developed herein may have broad application potential for evaluating the efficiency of precursor controls and further mitigating O3 pollution, in particular, for regions where comprehensive photochemical studies are unavailable.

Detection and Prediction of the Early Thermal Runaway and Control of the Li-Ion Battery by the Embedded Temperature Sensor Array.

Sorts of Li-ion batteries (LIB) have been becoming important energy supply and storage devices. As a long-standing obstacle, safety issues are limiting the large-scale adoption of high-energy-density batteries. Strategies covering materials, cell, and package processing have been paid much attention to. Here, we report a flexible sensor array with fast and reversible temperature switching that can be incorporated inside batteries to prevent thermal runaway. This flexible sensor array consists of PTCR ceramic sensors combined with printed PI sheets for electrodes and circuits. Compared to room temperature, the resistance of the sensors soars nonlinearly by more than three orders of magnitude at around 67 °C with a 1 °C/s rate. This temperature aligns with the decomposition temperature of SEI. Subsequently, the resistance returns to normal at room temperature, demonstrating a negative thermal hysteresis effect. This characteristic proves advantageous for the battery, as it enables a lower-temperature restart after an initial warming phase. The batteries with an embedded sensor array could resume their normal function without performance compromise or detrimental thermal runaway.

Trough polymyxin B plasma concentration is an independent risk factor for its nephrotoxicity.

AIMS: Data regarding clinical pharmacokinetic/toxicodynamic (PK/TD) of polymyxin B is short of direct quantitative data. This study aims to investigate the risk factors of polymyxin B associated acute kidney injury (AKI) and to assess the relationship between polymyxin B plasma levels and its nephrotoxicity. METHODS: A retrospective study was performed in adult patients treated with polymyxin B. Risk factors associated with AKI and plasma trough concentrations of polymyxin B were identified via medical record review. A multivariate logistic regression model was established and the risk of polymyxin B-associated AKI were predicted by a receiver operating characteristic curve, with maximal Youden index used to identify safety thresholds among the study population. RESULTS: Fifty-four adult patients were included in the study. AKI was detected in 14 patients during polymyxin B treatment (25.9%, 14 out of 54). Cmin (odds ratio [OR] 2.071; 95% confidence interval [CI] 1.235-3.472) and baseline serum creatinine (OR 1.024; 95% CI 1.005-1.043) were significant independent risk factors for developing AKI. The area under the ROC curve of the combined predictor was larger based on the above factors. When the Youden index was at maximum, the optimal cut-off point was 6.678 of the ROC curve. When Cmin ≥ 3.13 mg/L, the probability of AKI was more than 50%. CONCLUSION: In this study, when the calculated combined predictor value was >6.678, there was an increased risk of AKI. Maintaining a polymyxin B Cmin level below 3.13 mg/L may be helpful in reducing the incidence of polymyxin B associated nephrotoxicity.

Intraventricular colistin sulphate as a last resort therapy in a patient with multidrug-resistant Acinetobacter baumannii induced post-neurosurgical ventriculitis.

Limited therapeutic options exist for multidrug-resistant/extensively drug-resistant Acinetobacter baumannii (MDR/XDR-Ab) meningitis/ventriculitis. A combination of intravenous and intraventricular (IVT)/intrathecal (IT) polymyxins achieves good therapeutic outcomes for cases of healthcare-associated MDR/XDR-Ab meningitis/ventriculitis. Colistin is commercially available as colistin sulphate and its sulphomethylated derivative. However, the effect and safety of colistin sulphate in the treatment of MDR/XDR-Ab meningitis/ventriculitis has not been reported. We report on a 66-year-old male patient who developed post-neurosurgical ventriculitis caused by MDR-Ab. IVT concomitant intravenous colistin sulphate was used as a last-resort antimicrobial therapy, the patient's ventriculitis was dramatically improved, and the concentrations of CSF colistin were higher than the MIC breakpoint throughout the treatment. Meanwhile, no nephrotoxicity or neurotoxicity was observed during the treatment.

Sustained high atmospheric Hg level in Beijing during wet seasons suggests that anthropogenic pollution is continuing: Identification of potential sources.

Gaseous elemental Hg (GEM), particulate bound Hg (PBM), and gaseous oxidized Hg (GOM) were monitored at an urban site in Beijing, China during wet seasons (July-November) of 2021. The mean (± standard deviation) GEM, PBM, and GOM concentrations were 3.45 ± 1.27 ng m-3, 48.2 ± 88.6 pg m-3, and 13.7 ± 55.0 pg m-3, respectively. GEM level was stable (generally 3.0-4.0 ng m-3) and the average concentration was about twice that of the background level in Beijing, while the occasionally very high PBM and GOM concentrations (>1000 pg m-3) suggest pollution events. Moreover, GEM, CO, and NO2 exhibit a conspicuous similar diurnal trend with lower values during daytime compared to nighttime under the combined influence of anthropogenic emissions and meteorological factors, and the significantly positive relationship between them indicates that they had similar or common sources. However, the diurnal pattern of reactive Hg (i.e., RM = PBM + GOM) was not pronounced. Both cluster and potential source contribution function analyses show that southern Beijing, Tianjin, as well as central and east Hebei provinces were the dominant source regions for elevated GEM at this monitoring site. The dominant reason for the elevated GEM level (generally >3.5 ng m-3) during pollution event is that majority of air masses originated from the southern polluted regions of this sampling site and traveled at low heights, while the long-range transport of upper clean air masses and continuous high traveling heights were attributed to the low GEM level (<2.0 ng m-3) during clean event. Positive matrix factorization results reveal that regional transport of coal fired air pollutants and local vehicle emissions were the dominant contributors to elevated GEM level, while RM mainly originated from local sources.

Volatile organic compounds emission in the rubber products manufacturing processes.

Volatile organic compounds (VOCs) emission from rubber products manufacture processes, mixing, shaping and vulcanization were investigated in four rubber products factories in China. The source emission air was passively sampled by pre-vacuumized stainless steel canister and analyzed by gas chromatography-mass spectrometry-flame ionization detection (GC/MS-FID). The species profile of 107 VOCs in the emission processes were obtained. We calculated the photochemical ozone formation potential (OFP) and carcinogenic risk (CR) of the VOCs for each manufacture process. The results showed that mixing process mainly released dichloromethane (14.53%), carbon disulfide (CS2) (6.88%), styrene (5.72%), 4-methyl-2-pentanone (5.22%) and naphthalene (3.69%) for solvents used and raw rubber degradation in the process. The C6-C8 alkanes, especially heptane and isomers of heptane (44.71%), were dominated in shaping process. The major species released from vulcanization process were carbon disulfide (29.72%), naphthalene (8.17%), acetone (7.73%) and dichloromethane (4.26%). VOCs emitted from vulcanization process had the highest OFP, which contributed by naphthalene, m/p-xylene, o-xylene and carbon disulfide. VOCs emission from mixing process had the highest CR, and 1,2-dibromoethane, 1,2-dichlorethane and 1,3-butadiene were the main contributors to CR. We also estimated the total VOCs emissions into the atmosphere from tires manufacturing in China, which were 7.58 × 105 t in 2018 and contributed about 9% of total industry processes VOCs emissions.

Measurement of the Vertical Distribution of Gaseous Elemental Mercury Concentration in Soil Pore Air of Subtropical and Temperate Forests.

Solid-gas-water phase partitioning of mercury (Hg) and the processes governing its diffusivity within soils are poorly studied. In this study, landscape and forest species dependences of gaseous elemental Hg (Hg(0)) in soil profiles (0-50 cm) were investigated over four seasons in eight subtropical (130 days) and temperate (96 days) forest plots. The vertical soil pore Hg(0) concentrations differed between subtropical (Masson pine, broad-leaved forest, and open field) and temperate (Chinese pine, larch, mixed broad-leaf forests, and open field) catchments, with annual averages ranging from 6.73 to 15.8 and 0.95 to 2.08 ng m-3, respectively. The highest Hg(0) concentrations in soil gas consistently occurred in the upper mineral or organic horizons, indicating immobilization of Hg(0) in mineral soils. A strongly positive relationship between pore Hg(0) concentrations and ratios of Hg to organic matter (SOM) in soils suggests that the vertical distribution of Hg(0) is related to soil Hg(0) formation by Hg(II) reduction and sorption to SOM. Temperature was also an important driver of Hg(0) production in soil pores. Based on measurements of soil-air Hg(0) exchange, diffusion coefficients (Ds) of Hg(0) between soil and atmosphere were calculated for field sites, providing a foundation for future development and validation of terrestrial Hg models.

Planular-vertical distribution and pollution characteristics of cropland soil Hg and the estimated soil-air exchange fluxes of gaseous Hg over croplands in northern China.

As an important reservoir of mercury (Hg), cropland play an important role in the Hg cycle, but it was poorly understood in northern China. The major objectives of this study are to ascertain the distribution characteristics of soil Hg and then assess its pollution level and potential risk, and further evaluate the role of cropland in northern China in the global soil-air exchange of Hg based on the simulation experiments and regional survey. The average Hg concentration in surface soils of the 30 sites in northern China was 116.1 ± 135.8 ng g-1, which was significantly higher than background values. The surface soils show a significant spatial heterogeneity in Hg concentration, and the Hg levels near provincial capitals were higher than those at corresponding prefecture-level cities, revealing that the soil Hg levels were closely associated with the local industrial and economic development. Profile data shows that topsoil Hg concentration was significantly higher than those in deeper layers at most of sites, indicating the more serious pollution situation in recent years. Generally, the higher the surface soil Hg concentration, the more obvious this top-bottom decreasing trend. The planular-vertical distribution patterns of TOM share similar trends as those of soil Hg concentration, indicating Hg concentration was closely associated with TOM content. Statistical results show that the mean CF, Eri, and Igeo values were 4.0 ± 5.0, 161 ± 198, 0.76 ± 1.34, respectively, and more than two thirds of sampling sites were moderately and considerably polluted. The mean annual accumulative flux of Hg in the northern China was 20.9 ± 43.8 µg m-2 yr-1, and the total net emission fluxes of Hg from the croplands in six provinces were 8.37 ton yr-1. This indicates that although the cropland occasionally acts as a sink, it represents an important natural source of atmospheric Hg as a whole.

Mercury accumulation response of rice plant (Oryza sativa L.) to elevated atmospheric mercury and carbon dioxide.

New observations and updated models now suggest terrestrial ecosystems are net sink of atmospheric mercury (Hg), and the critical constrained process to identify the strengths of terrestrial sink is whether the large amount of Hg stored in vegetation originates from the soil as well as from the atmosphere. In this study, field open top chambers (OTCs) experiments reveal that rice plant can assimilate gaseous elemental mercury (GEM, Hg0) from the atmosphere through stomata, and Hg concentrations in rice leaves, upper and bottom stalks and grains increased with Hg0 levels in air, showing significantly quadratic linear relationships. Coupling field stable isotope soil amendment experiments, atmospheric source of Hg in rice plant is quantified with more than 90% of Hg accumulation in rice aboveground biomass from air and approximately 80% of rice root Hg from soil. Furthermore, elevated atmospheric carbon dioxide (CO2) exposure led to lower Hg concentration in rice tissues through reduction stomatal conductance of rice leaf, and subsequently impact the capacity of Hg storage in rice aboveground parts from the atmosphere. The findings from experiments provide a foundation for future quantification of atmospheric sink of crops in local and larger scales and comprehensive evaluation atmosphere - terrestrial processes and exposure risks in the global Hg cycling.

[Research progress on Pheretima and earthworms with related origin].

Through literature analysis of Pheretima and its origin-related earthworm,this study summarized the progress on Pheretima in textual criticism of origin,origin identification,effective components,detection of harmful components,and pharmacological effects,which can lay a basis for further research on Pheretima. Through literature research,the authors found that Pheretima was first recorded in Secret Formulary for Traumatology and Fracture Taught by Immortal written by LIN Daoren in Tang Dynasty rather than the Taiping Holy Prescriptions for Universal Relief in Song Dynasty. The latest techniques for origin identification include microscopic trait identification,DNA barcoding,and HPLC. The main effective components of Pheretima are proteins,polypeptides,enzymes,nucleotides,amino acids,and trace elements. According to recent studies,Pheretima has anti-pulmonary and anti-renal interstitial fibrosis,respiratory syncytial virus-inhibiting,human hypertrophic scar fibroblast proliferation-suppressing,and mouse embryonic fibroblast proliferation-promoting effects. Moreover,Pheretima can prevent colitis-induced colon cancer by inhibiting the activation of COX-2/PGE2/ß-catenin signaling pathway. METHODS:: for detecting the harmful components and their residues( organic pollutant polychlorinated biphenyl,heavy metals) and bacteria in Pheretima,have been established. Pheretima,mainly derived from wild earthworms,has remarkable clinical efficacy. However,the wild resource is in short supply and artificial culture is expected to be a promising solution.

Opposing roles of miR-294 and MBNL1/2 in shaping the gene regulatory network of embryonic stem cells.

Alternative pre-mRNA splicing plays important roles in regulating self-renewal and differentiation of embryonic stem cells (ESCs). However, how specific alternative splicing programs are established in ESCs remains elusive. Here, we show that a subset of alternative splicing events in ESCs is dependent on miR-294 expression. Remarkably, roughly 60% of these splicing events are affected by the depletion of Muscleblind-Like Splicing Regulator 1 and 2 (Mbnl1/2). Distinct from canonical miRNA function, miR-294 represses Mbnl1/2 through both posttranscriptional and epigenetic mechanisms. Furthermore, we uncover non-canonical functions of MBNL proteins that bind and promote the expression of miR-294 targets, including Cdkn1a and Tgfbr2, thereby opposing the role of miR-294 in regulating cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT). Our study reveals extensive interactions between miRNAs and splicing factors, highlighting their roles in regulating cell type-specific alternative splicing and defining gene expression programs during development and cellular differentiation.

Permafrost Thaw Dominates Mercury Emission in Tibetan Thermokarst Ponds.

Increasing evidence shows that warming is driving Hg release from the cryosphere. However, Hg cycling in thawing permafrost is less understood to date. Here we show that permafrost thaw dominantly supplied no-run thermokarst ponds by permafrost melt waters (PMWs) with high concentration of photoreducible Hg (PRHg) and subsequently controlled Hg(0) emissions in the Tibetan Plateau. This study was motivated by field survey suggesting that thermokarst ponds as recipient aquatic systems of PMWs could be an active converter of PRHg to Hg(0). Annual Hg mass balance in three seasonally ice-covered thermokarst ponds suggests that PMWs were the dominant input (81.2% to 91.2%) of PRHg in all three thermokarst ponds, and PRHg input would be a constraint of Hg(0) emission owing to the fast photoreduction of PRHg to Hg(0) in the water column. Annual Hg(0) emission in the thermokarst ponds of study region was conservatively estimated to increase by 15% over the past half century. Our findings highlight that climate-induced landscape disturbances and changes in hydrogeochemical processes in climate-sensitive permafrost will quickly and in situ drive Hg stored in permafrost for a very long time into the modern day Hg cycle, which potentially offsets the anthropogenic Hg mitigation policies.