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Abstract Background To explore the value of dual-energy computed tomography (DECT) in differentiating pathological subtypes and the expression of immunohistochemical markers Ki-67 and thyroid transcription factor 1 (TTF-1) in patients with non-small cell lung cancer (NSCLC). Methods Between July 2022 and May 2024, patients suspected of lung cancer who underwent two-phase contrast-enhanced DECT were prospectively recruited. Whole-tumor volumetric and conventional spectral analysis were utilized to measure DECT parameters in the arterial and venous phase. The DECT parameters model, clinical-CT radiological features model, and combined prediction model were developed to discriminate pathological subtypes and predict Ki-67 or TTF-1 expression. Multivariate logistic regression analysis was used to identify independent predictors. The diagnostic efficacy was assessed by the area under the receiver operating characteristic curve (AUC) and compared using DeLong’s test. Results This study included 119 patients (92 males and 27 females; mean age, 63.0 ± 9.4 years) who was diagnosed with NSCLC. When applying the DECT parameters model to differentiate between adenocarcinoma and squamous cell carcinoma, ROC curve analysis indicated superior diagnostic performance for conventional spectral analysis over volumetric spectral analysis (AUC, 0.801 vs. 0.709). Volumetric spectral analysis exhibited higher diagnostic efficacy in predicting immunohistochemical markers compared to conventional spectral analysis (both P

Global warming in tandem with surface albedo reduction caused by black carbon (BC) deposition on glaciers accelerated glacier melting; however, their respective contributions remain unclear. Glaciers in the Qilian Mountains are crucial for the development of oases in the Hexi Corridor; however, their area has decreased by more than 20% over the past half-century. Thus, this study developed a dynamic deposition model for light-absorbing particles (LAPs), coupled with a surface energy and mass balance model. We comprehensively assessed the effects of BC and warming on the melting of a typical glacier in the Qilian Mountains based on the coupled model. BC on the glacier surface caused 13.1% of annual glacier-wide melting, of which directly deposited atmospheric BC reduced the surface albedo by 0.02 and accounted for 9.1% of glacier melting. The air temperature during 2000–2010 has increased by 1.5 °C relative to that during the 1950s, accounting for 51.9% of current glacier melting. Meanwhile, BC emission have increased by 4.6 times compared to those of the early Industrial Revolution recorded in an ice core, accounting conservatively for 6.3% of current glacier melting. Mitigating BC emissions has a limited influence on current glacier melting; however, in the long-term, mitigation should exert a noteworthy impact on glacier melting through the self-purification of glaciers.

Abstract Background Cervical cancer is a prevalent malignancy and an important health concern worldwide. Recent research has highlighted the potential impact of metabolic factors, such as hyperlipidemia and diabetes, on cancer progression, increased mortality, and patient outcomes. However, insufficient data have been reported regarding their relationship with cervical cancer. This study aimed to investigate the relationships between metabolic disorders, including dyslipidemia, dysglycemia, and metabolic syndrome, and survival in patients with cervical cancer. Methods We retrospectively analyzed demographic information, clinical characteristics, and metabolic health indicators of patients with cervical cancer. Patients were categorized into groups based on specific metabolic conditions: high triglyceride, high low-density lipoprotein, high cholesterol, and diabetes groups. Additionally, the presence of metabolic syndrome and other metabolic comorbidities was recorded. The log-rank test was used to compare survival rates between different patient groups and identify associated risk factors. Survival curves generated via the Cox proportional hazards model were used to evaluate the associations between metabolic parameters and survival. Results The Cox proportional hazards model was used to analyze data from 840 patients with cervical cancer between 28 and 72 years old who underwent surgery. The hazard ratio (HR) of mortality was 1.804 (95% CI 1.394–2.333, p

Tumorigenesis and metastasis are highly dependent on the interactions between the tumor and the surrounding microenvironment. In 3D matrix, the fibrous structure of the extracellular matrix (ECM) undergoes dynamic remodeling during tumor progression. In particular, during the late stage of tumor development, the fibers become more aggregated and oriented. However, it remains unclear how cancer cells respond to the organizational change of ECM fibers and exhibit distinct morphology and behavior. Here, we used electrospinning technology to fabricate biomimetic ECM with distinct fiber arrangements, which mimic the structural characteristics of normal or tumor tissues and found that aligned and oriented nanofibers induce cytoskeletal rearrangement to promote directed migration of cancer cells. Mechanistically, caveolin-1(Cav-1)-expressing cancer cells grown on aligned fibers exhibit increased integrin β1 internalization and actin polymerization, which promoted stress fiber formation, focal adhesion dynamics and YAP activity, thereby accelerating the directional cell migration. In general, the linear fibrous structure of the ECM provides convenient tracks on which tumor cells can invade and migrate. Moreover, histological data from both mice and patients with tumors indicates that tumor tissue exhibits a greater abundance of isotropic ECM fibers compared to normal tissue. And Cav-1 downregulation can suppress cancer cells muscle invasion through the inhibition of YAP-dependent mechanotransduction. Taken together, our findings revealed the Cav-1 is indispensable for the cellular response to topological change of ECM, and that the Cav-1/YAP axis is an attractive target for inhibiting cancer cell directional migration which induced by linearization of ECM fibers.

Objective: Due to the high drug resistance and relapse rate of T-cell acute lymphoblastic leukemia (T-ALL), the prognosis is usually poor. Therefore, there is an urgent need to find safer and more effective therapeutic drugs. Huaier and its preparations, as adjuvant drugs, have been widely used in the treatment of solid tumors and other diseases. However, the application of Huaier in leukemia is rarely reported. In this study, we investigated the anti-tumor effect of Huaier on T- ALL and its underlying mechanism. Methods: Jurkat and MOLT-4 cells were treated with Huaier. Cell viability was evaluated by CCK-8 assay. The morphological changes of apoptotic cells were observed by Hoechst 33258 staining. Cell apoptosis was analyzed by flow cytometry. The expression levels of related proteins were assessed by Western blot. Results: The results showed that Huaier significantly inhibited the proliferation of Jurkat and MOLT-4 cells in a dose- and time-dependent manner, with IC50 of 2.37 ± 0.10 and 1.93 ± 0.07 mg/mL at 48 h, respectively. Morphological changes and increased number of apoptotic cells were observed by Hoechst 33258 staining and flow cytometry. The apoptosis rates of Jurkat and MOLT-4 cells in 4 mg/mL group were 50.67 ± 1.36 % and 49.97 ± 5.43 %, respectively. Huaier promoted the expression of Cytochrome c, Cleaved Caspase-3, Cleaved PARP, p53, LC3-Ⅱ and p62 proteins, while inhibited the expression of SIRT1, ATG7 and Beclin 1 proteins. Treatment with SRT1720 (SIRT1 agonist) combined with Huaier rescued Huaier-induced apoptosis and increased the expression of autophagy-related proteins. Conclusion: Huaier inhibits autophagy and promotes apoptosis of T-ALL cells by down-regulating SIRT1, which may be a potential drug for the treatment of T-ALL.

Cataract is a common eye disease characterized by lens opacity, leading to blurred vision and progressive blindness of the eye. Factors affecting the development of cataracts include nutrition, oxidative stress, micronutrients and inflammatory factors, and also include genetics, toxicity, infrared exposure, hyperuricemia, and mechanical injuries. Among the nutritional factors, a balanced diet, vegetarian diet, dairy products and vegetables are protective against cataracts; high-sodium diet, high intake of carbohydrates and polyunsaturated fatty acids may increase the risk of cataracts; and increased intake of proteins, especially animal proteins, may prevent nuclear cataracts. Intake of antioxidants such as β-carotene, lutein, or zeaxanthin is associated with a reduced risk of cataracts. Minerals such as zinc, selenium, calcium and sodium have also been associated with cataract development. Oxidative stress plays an important role in the development of cataracts and is associated with several antioxidative enzymes and biomarkers such as glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Insulin resistance is also an essential risk factor for cataracts, especially in diabetic patients. In conclusion, understanding these influencing factors helps us to better prevent cataracts. And in this article, we will focus on the important factor of diet and nutrition for a detailed discussion.

MAFLD has become a major global health problem and is the leading cause of liver disease worldwide. The disease progresses from a simple fatty liver to gradual fibrosis, which progresses to cirrhosis and even hepatocellular liver cancer. However, the methods currently used for diagnosis are invasive and do not facilitate clinical assessment of the condition. As a result, research on markers for the diagnosis of MAFLD is increasing. In addition, there are no clinical medications for the treatment of MAFLD, and lifestyle interventions remain effective in the prevention and treatment of MAFLD. In this review, we attempt to make a summary of the emerging diagnostic indicators and effective lifestyle interventions for MAFLD and to provide new insights into the diagnosis and treatment of MAFLD.

Metabolic syndrome has become major health problems in recent decades, and natural compounds receive considerable attention in the management of metabolic syndrome. Among them, naringin is abundant in citrus fruits and tomatoes. Many studies have investigated the therapeutic effects of naringin in metabolic syndrome. This review discusses in vitro and in vivo studies on naringin and implications for clinical trials on metabolic syndrome such as diabetes mellitus, obesity, nonalcoholic fatty liver disease, dyslipidemia, and hypertension over the past decades, overviews the molecular mechanisms by which naringin targets metabolic syndrome, and analyzes possible correlations between the different mechanisms. This review provides a theoretical basis for the further application of naringin in the treatment of metabolic syndrome.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) has emerged as a significant global health concern, representing a major cause of liver disease worldwide. This condition spans a spectrum of histopathologic stages, beginning with simple fatty liver (MAFL), characterized by over 5% fat accumulation, and advancing to metabolic (dysfunction)-associated steatohepatitis, potentially leading to hepatocellular carcinoma. Despite extensive research, there remains a substantial gap in effective therapeutic interventions. This condition’s progression is closely tied to micronutrient levels, crucial for biological functions like antioxidant activities and immune efficiency. The levels of these micronutrients exhibit considerable variability among individuals with MAFLD. Moreover, the extent of deficiency in these nutrients can vary significantly throughout the different stages of MAFLD, with disease progression potentially exacerbating these deficiencies. This review focuses on the role of micronutrients, particularly vitamins A, D, E, and minerals like iron, copper, selenium, and zinc, in MAFLD’s pathophysiology. It highlights how alterations in the homeostasis of these micronutrients are intricately linked to the pathophysiological processes of MAFLD. Concurrently, this review endeavors to harness the existing evidence to propose novel therapeutic strategies targeting these vitamins and minerals in MAFLD management and offers new insights into disease mechanisms and treatment opportunities in MAFLD.

Machine learning (ML) has shown its effectiveness in handling multi-geoinformation. Yet, the black-box nature of ML algorithms has restricted their widespread adoption in the domain of mineral prospectivity mapping (MPM). In this paper, methods for interpreting ML model predictions are introduced to aid ML-based MPM, with the goal of extracting richer insights from the ML modeling of an exploration geochemical dataset. The partial dependence plot (PDP) and accumulated local effect (ALE) plot, along with the SHAP value analysis, were utilized to demonstrate the application of random forest (RF) modeling within both regression and classification frameworks. Initially, the random forest regression (RFR) model established the relationship between the concentrations of Au and those of elements such as As, Sb, and Hg in the study area, and from this model, the most important geochemical elements and their quantitative relationships with Au were revealed by their contributions in the modeling through PDP and ALE analyses. Secondly, the RF classification modeling established the relationships of mineralization occurrences (i.e., known mineral deposits) with geochemical elements (i.e., Au, As, Sb, Hg, Cu, Pb, Zn, and Ag), as did RFR modeling. The most important geochemical elements for indicating regional Au mineralization and the trajectories of PDP and ALE reached a consensus that As and Sb contributed the most, both in the regression and classification modeling, with regard to Au mineralization. Finally, the SHAP values illustrated the behavior of the training samples (i.e., known mineral deposits) in RF modeling, and the resulting prospectivity map was evaluated using receiver operating characteristics.

Abstract Warming has been and is being enhanced at high latitudes or high elevations, whereas the quantitative estimation for warming from altitude and latitude effects has not been systematically investigated over Antarctic Ice Sheet, which covers more than 27 degrees of latitude and 4000 m altitude ranges. Based on the monthly surface air temperature data (1958–2020) from ERA5 reanalysis, this work aims to explore whether elevation-dependent warming (EDW) and latitude-dependent warming (LDW) exist. Results show that both EDW and LDW have the cooperative effect on Antarctic warming, and the magnitude of EDW is stronger than LDW. The negative EDW appears between 250 m and 2500 m except winter, and is strongest in autumn. The negative LDW occurs between 83 °S and 90 °S except in summer. Moreover, the surface downward long-wave radiation that related to the specific humidity, total cloud cover and cloud base height is a major contributor to the EDW over Antarctica. Further research on EDW and LDW should be anticipated to explore the future Antarctic amplification under different emission scenarios.

In this paper, firstly, according to the requirements of static monitoring of bolt tightening quality, the bolt tightening process can be divided into four stages: snug, elastic deformation, yielding and plastic deformation, and the SLAM technology is applied to bolt monitoring modeling and building engineering modeling. Next, the pre-tightening force for the bolt is measured using the waveform expansion method, and the bolt tightening index can be determined. Then, all the collected bolt data are randomly combined into two categories of loosening and tightening to form a training data set, and the improved intelligent data algorithm is used to train and predict them. The results show a linear correlation between tightening degree x |τɛ| and preload force change ΔF under 0.31kN and 0.22kN loading gradients, and the linear correlation coefficient of the fitted curve is greater than 0.9215. The results of the data analysis verify the correctness of the theoretical analysis.

This study explored the main active ingredients and the underlying mechanism of TwHF in the treatment of ALL by network pharmacology and molecular docking. TCMSP, OMIM and GeneCards databases were used to obtain active ingredients of TwHF to predict related targets of TwHF and ALL. Cytoscape and STRING databases were used to construct Ingredient-target-disease and PPI networks, respectively. Enrichment analysis of GO and KEGG was conducted by Bioconductor database. Molecular docking was performed using the Autodock platform to predict the binding of the active components to key action targets.CCK-8 assay was performed to measure the effects of drugs on the proliferation of ALL cells. The ingredient-target-disease network contained 16 compounds and 43 corresponding targets. Key targets included VEGFA, CASP3, RELA, ESR1, BCL2, and MAPK8. There were 79 GO items in the GO enrichment analysis (p

Abstract The polar amplification (PA) has become the focus of climate change. However, there are seldom comparisons of amplification among Earth’s three poles of Arctic (latitude higher than 60 °N), Antarctica (Antarctic Ice Sheet) and the Third Pole (the High Mountain Asia with the elevation higher than 4000 m) under different socioeconomic scenarios. Based on CMIP6 multi-model ensemble, two types of PA index (PAI) have been defined to quantify the PA intensity and variations, and PAI1/PAI2 is defined as the ratio of the absolute value of surface air temperature linear trend over Earth’s three poles and that for global mean/over other regions except Earth’s three poles. Arctic warms fastest in winter and weakest in summer, followed by the Third Pole, and Antarctica warms least. The similar phenomenon proceeds when global warming of 1.5–2.0 °C, and 2.0–3.0 °C above pre-industrial levels. After removing the Earth’s three poles self-influence, all the PAI2s increase much more obviously relative to the PAI1s, especially the Antarctic PAI. Earth’s three poles warm faster than the other regions. With the forcing increasing, PA accelerates much more over Antarctica and the Third Pole, but becomes weaker over Arctic. This demonstrates that future warming rate might make a large difference among Earth’s three poles under different scenarios.

The clinical outcomes of cancer nanovaccine have been largely impeded owing to the low antigen-specific T cell response rate and acquired resistance caused by the immunosuppressive tumor microenvironment (TME). Here, we reported a tumor acidity-responsive nanovaccine to remodel the immunosuppressive TME and expand the recruitment of tumor infiltrating lymphocytes (TILs) using hybrid micelles (HM), which encapsulated colony stimulating factor 1 receptor (CSF1-R) inhibitor BLZ-945 and indoleamine 2,3-dioxygenase (IDO) inhibitor NLG-919 in its core and displayed a model antigen ovalbumin (OVA) on its surface (denoted as BN@HM-OVA). The bioactive nanovaccine is coated with a polyethylene glycol (PEG) shell for extending nanoparticle circulation. The shell can be shed in response to the weakly acidic tumor microenvironment. The decrease in size and the increase in positive charge may cause the deep tumor penetration of drugs. We demonstrated that the bioactive nanovaccine dramatically enhance antigen presentation by dendritic cells (DCs) and drugs transportation into M1-like tumor-associated macrophages (TAMs) and tumor cells via size reduction and increasing positive charge caused by the weakly acidic TME. Such bioactive nanovaccine could remodel the immunosuppressive TME into an effector T cells favorable environment, leading to tumor growth inhibition in prophylactic and therapeutic E.G7-OVA tumor models. Furthermore, combining the bioactive nanovaccine with simultaneous anti-PD-1 antibody treatment leads to a long-term tumor inhibition, based on the optimal timing and sequence of PD-1 blockade against T cell receptor. This research provides a new strategy for the development of efficient cancer immunotherapy.

Abstract Closely related with microbial activities, soil developments along the glacier forelands are generally considered a carbon sink; however, those of continental glacier forelands remain unclear. Continental glaciers are characterized by dry conditions and low temperature that limit microbial growth. We investigated the carbon characteristics along a chronosequence of the Laohugou Glacier No. 12 foreland, a typical continental glacier on the Tibetan Plateau, by analyzing soil bacterial community structure and microbial carbon-related functional potentials. We found an unexpected carbon loss in which soil organic carbon decreased from 22.21 g kg−1 to 10.77 g kg−1 after receding 50 years. Structural equation modeling verified the important positive impacts from bacterial community. Lower carbon fixation efficiency along the chronosequence was supported by less autotrophic bacteria and carbon fixation genes relating to the reductive tricarboxylic acid cycle. Lower carbon availability and higher carbon requirements were identified by an increasing bacterial copy number and a shift of the dominant bacterial community from Proteobacteria and Bacteroidetes (r-strategists) to Actinobacteria and Acidobacteria (K-strategists). Our findings show that the carbon loss of continental glacier foreland was significantly affected by the changes of bacterial community, and can help to avoid overestimating the carbon sink characteristics of glacier forelands in climate models.

Fluoride is a common contaminant of groundwater and agricultural commodity, which poses challenges to animal and human health. A wealth of research has demonstrated its detrimental effects on intestinal mucosal integrity; however, the underlying mechanisms remain obscure. This study aimed to investigate the role of the cytoskeleton in fluoride-induced barrier dysfunction. After sodium fluoride (NaF) treatment of the cultured Caco-2 cells, both cytotoxicity and cytomorphological changes (internal vacuoles or massive ablation) were observed. NaF lowered transepithelial electrical resistance (TEER) and enhanced paracellular permeation of fluorescein isothiocyanate dextran 4 (FD-4), indicating Caco-2 monolayers hyperpermeability. In the meantime, NaF treatment altered both the expression and distribution of the tight junction protein ZO-1. Fluoride exposure increased myosin light chain II (MLC2) phosphorylation and triggered actin filament (F-actin) remodeling. While inhibition of myosin II by Blebbistatin blocked NaF-induced barrier failure and ZO-1 discontinuity, the corresponding agonist Ionomycin had effects comparable to those of fluoride, suggesting that MLC2 serves as an effector. Given the mechanisms upstream of p-MLC2 regulation, further studies demonstrated that NaF activated RhoA/ROCK signaling pathway and myosin light chain kinase (MLCK), strikingly increasing the expression of both. Pharmacological inhibitors (Rhosin, Y-27632 and ML-7) reversed NaF-induced barrier breakdown and stress fiber formation. The role of intracellular calcium ions ([Ca2+]i) in NaF effects on Rho/ROCK pathway and MLCK was investigated. We found that NaF elevated [Ca2+]i, whereas chelator BAPTA-AM attenuated increased RhoA and MLCK expression as well as ZO-1 rupture, thus, restoring barrier function. Collectively, abovementioned results suggest that NaF induces barrier impairment via Ca2+-dependent RhoA/ROCK pathway and MLCK, which in turn triggers MLC2 phosphorylation and rearrangement of ZO-1 and F-actin. These results provide potential therapeutic targets for fluoride-induced intestinal injury.

Polar amplification appears in response to greenhouse gas forcing, which has become a focus of climate change research. However, polar amplification has not been systematically investigated over the Earth’s three poles (the Arctic, Antarctica, and the Third Pole). An index of polar amplification is employed, and the annual and seasonal variations of land surface temperature over the Earth’s three poles are examined using MODIS (Moderate Resolution Imaging Spectroradiometer) observations for the period 2001–2018. As expected, the warming of the Arctic is most conspicuous, followed by the Third Pole, and is weakest in Antarctica. Compared to the temperature changes for the global land region, positive polar amplification appears in the Arctic and the Third Pole on an annual scale, whereas Antarctic amplification disappears, with a negative amplification index of −0.72. The polar amplification for the Earth’s three poles shows seasonal differences. Strong Arctic amplification appears in boreal spring and winter, with a surface warming rate of more than 3.40 times the global mean for land regions. In contrast, the amplification of the Third Pole is most conspicuous in boreal summer. The two poles located in the Northern Hemisphere have the weakest amplification in boreal autumn. Differently from the positive amplification for the Arctic and the Third Pole in all seasons, the faster variations in Antarctic temperature compared to the globe only appear in austral autumn and winter, and the amplification signal is negative in these seasons, with an amplification index of −1.68 and −2.73, respectively. In the austral winter, the strong negative amplification concentrates on West Antarctica and the coast of East Antarctica, with an absolute value of amplification index higher than 5 in general. Generally, the polar amplification is strongest in the Arctic except from June to August, and Antarctic amplification is the weakest among the Earth’s three poles. The Earth’s three poles are experiencing drastic changes, and the potential influence of climate change should receive attention.

Abstract Dynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence, progression, invasion, and metastasis of solid tumors. In this process, the tumor microenvironment (TME) fractures cellular and matrix architecture normality through biochemical and mechanical means, abetting tumorigenesis and treatment resistance. Tumor cells sense and respond to the strength, direction, and duration of mechanical cues in the TME by various mechanotransduction pathways. However, far less understood is the comprehensive perspective of the functions and mechanisms of mechanotransduction. Due to the great therapeutic difficulties brought by the mechanical changes in the TME, emerging studies have focused on targeting the adverse mechanical factors in the TME to attenuate disease rather than conventionally targeting tumor cells themselves, which has been proven to be a potential therapeutic approach. In this review, we discussed the origins and roles of mechanical factors in the TME, cell sensing, mechano‐biological coupling and signal transduction, in vitro construction of the tumor mechanical microenvironment, applications and clinical significance in the TME.

IntroductionBacteria are an essential component of glacier-fed ecosystems and play a dominant role in driving elemental cycling in the hydrosphere and pedosphere. However, studies of bacterial community composition mechanisms and their potential ecological functions from the alluvial valley of mountain glaciers are extremely scarce under cold and arid environments.MethodsHere, we analyzed the effects of major physicochemical parameters related to soil on the bacterial community compositions in an alluvial valley of the Laohugou Glacier No. 12 from the perspective of core, other, and unique taxa and explored their functional composition characteristics.Results and discussionThe different characteristics of core, other, and unique taxa highlighted the conservation and difference in bacterial community composition. The bacterial community structure of the glacial alluvial valley was mainly affected by the above sea level, soil organic carbon, and water holding capacity. In addition, the most common and active carbon metabolic pathways and their spatial distribution patterns along the glacial alluvial valley were revealed by FAPTOTAX. Collectively, this study provides new insights into the comprehensive assessment of glacier-fed ecosystems in glacial meltwater ceasing or glacier disappearance.

Objective: To explore the mechanism of PG against acute lymphoblastic leukaemia (ALL) by network pharmacology and experimental verification in vitro. Methods: First, the biological activity of PG against B-ALL was determined by CCK-8 and flow cytometry. Then, the potential targets of PG were obtained from the PharmMapper database. ALL-related genes were collected from the GeneCards, OMIM and PharmGkb databases. The two datasets were intersected to obtain the target genes of PG in ALL. Then, protein interaction networks were constructed using the STRING database. The key targets were obtained by topological analysis of the network with Cytoscape 3.8.0 software. In addition, the mechanism of PG in ALL was confirmed by protein‒protein interaction, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Furthermore, molecular docking was carried out by AutoDock Vina. Finally, Western blotting was performed to confirm the effect of PG on NALM6 cells. Results: PG inhibited the proliferation of NALM6 cells. A total of 174 antileukaemic targets of PG were obtained by network pharmacology. The key targets included AKT1, MAPK14, EGFR, ESR1, LCK, PTPN11, RHOA, IGF1, MDM2, HSP90AA1, HRAS, SRC and JAK2. Enrichment analysis found that PG had antileukaemic effects by regulating key targets such as MAPK signalling, and PG had good binding activity with MAPK14 protein (−8.9 kcal/mol). PG could upregulate the expression of the target protein p-P38, induce cell cycle arrest, and promote the apoptosis of leukaemia cells. Conclusion: MAPK14 was confirmed to be one of the key targets and pathways of PG by network pharmacology and molecular experiments.

Abstract Background Chronic myeloid leukemia (CML) is a myeloproliferative tumor originating from hematopoietic stem cells, and resistance to tyrosine kinase inhibitors (TKI) has become a major cause of treatment failure. Alternative drug therapy is one of the important ways to overcome TKI resistance. Hinokiflavone (HF) is a C-O-C type biflavonoid with low toxicity and antitumor activity. This study investigated the antitumor effect and possible mechanisms of HF in CML cells. Methods Cell viability was measured by CCK-8 assay. Cell apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blotting was used to assess protein expression levels. Results Our results showed that HF significantly inhibited the viability of K562 cells in a concentration- and time-dependent manner and induced G2/M phase arrest by up-regulating p21 and down-regulating Cdc2 protein. Furthermore, HF induced caspase-dependent apoptosis by activating JNK/p38 MAPK signaling pathway and inhibiting NF-κB activity. In addition, HF induced autophagy by increasing LC3-II expression and p62 degradation. Pretreatment with CQ, a late autophagy inhibitor, significantly increased the levels of LC3-II and p62 proteins and promoted cell survival. Conclusion HF shows a good anti-leukemia effect and is expected to become a potential therapeutic drug for CML.

With global warming, glaciers in the high mountains of China are retreating rapidly. However, few data have been reported on whether greenhouse gases from these glaciers are released into the atmosphere or absorbed by glacial meltwater. In this study, we collected meltwater and ice samples from Laohugou Glacier No. 12 in western China and measured CH4 and CO2 concentrations. Meltwater from the glacier terminus was continually sampled between 3 and 5 August 2020 to measure CH4 and CO2 concentrations. The results demonstrated that meltwater is a source of CH4 because the average saturations are over 100%. It could be concluded that CH4 in the atmosphere can be released by glacial meltwater. However, the CO2 saturations are various, and CO2 fluxes exhibit positive (released CO2) or negative (absorbed CO2) values because the water and atmospheric conditions are variable. More importantly, the CH4 and CO2 concentrations were higher in meltwater samples from the glacier terminus than in samples from the surface ice (including an ice core) and a surface stream. Although the meltwater effect from the upper part of the glacier cannot be excluded, we speculated that subglacial drainage systems with an anaerobic environment may represent the CH4 source, but it needs to be further investigated in the future. However, high mountain glaciers are currently ignored in global carbon budgets, and the increased melting of glaciers with global warming may accelerate the absorption of much more CO2 and lead to the release of CH4.

Global warming increases the frequency and intensity of climate extremes, but the changes in climate extremes over the Antarctic Ice Sheet (AIS) during different periods are unknown. Changes in surface temperature extreme indices (TN10p, TX10p, TN90p, TX90p, CSDI, WSDI, TNn, TNx, TXn, TXx and DTR) are assessed during 2021–2050 and 2071–2100 under SSP1-2.6, SSP2-4.5, SSP3-7.0 and SSP5-8.5, based on the multi-model ensemble mean (MMEM) from the Coupled Model Intercomparison Project Phase 6 (CMIP6). The extreme indices, excluding TXn and DTR, illustrate the opposite trend in the two periods in SSP1-2.6 over the AIS. Generally, the changes in extreme indices reflect the continued warming over AIS in the future, and the warming is projected to intensify in SSP3-7.0 and SSP5-8.5. The variations in the extreme indices exhibit regional differences. The Antarctic Peninsula displays rapid changes in TNn, TXn and DTR. In SSP5-8.5, the magnitudes of all climate index tendencies are greater during 2071–2100 than 2021–2050. The variations in TX10p, TX90p, TN10p, TN90p, WSDI and CSDI are faster in the Antarctic inland than in the other regions over the AIS. However, the decrease in the DTR is concentrated along the AIS coast and extends to the interior region, whereas the increasing trend occurs in the Antarctic inland. In West AIS, TX90p and TN90p rapidly increase during 2021–2050, whereas the rapid changing signals disappear in this region in 2071–2100. The dramatic changes in TNn, TXn and DTR occur at the Ross Ice Shelf during 2071–2100, indicating an increased risk of collapse. For TNx and TXx, the degree of warming in the later part of the 21st century is divided by the transantarctic mountains, and greater changes appear on the eastern side. Generally, Antarctic amplification of TNn, TXn and DTR is observed except under SSP1-2.6. In addition, TNx and TXx amplifications occur in SSP3-7.0 and SSP5-8.5.

Abstract Background This study aims to identify the causative strain of SARS-CoV-2 in a cluster of vaccine breakthroughs. Vaccine breakthrough by a highly transmissible SARS-CoV-2 strain is a risk to global public health. Methods Nasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) by qPCR (quantitative polymerase chain reaction) for Wuhan-Hu1 and alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant. GATK (genome analysis toolkit) variants were filtered with allele fraction ≥80 and min read depth 30x. Results Viral sequencing revealed an infection cluster of 6 vaccinated patients infected with the delta (B.1.617.2) SARS-CoV-2 variant. With no history of vaccine breakthrough, this suggests the delta variant may possess immune evasion in patients that received the Pfizer BNT162b2, Moderna mRNA-1273, and Covaxin BBV152. Conclusions Delta variant may pose the highest risk out of any currently circulating SARS-CoV-2 variants, with previously described increased transmissibility over alpha variant and now, possible vaccine breakthrough. Funding Parts of this work was supported by the National Institute of Allergy and Infectious Diseases (1U19AI144297) and Baylor College of Medicine internal funding.

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly worldwide; however, there are currently limited treatments for NAFLD. The disease spectrum includes simple fatty liver, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and progression to hepatocellular carcinoma (NASH-HCC). The therapeutic effects of NAFLD remain controversial. Although researchers have conducted studies on the pathogenesis of NAFLD, its pathogenesis and anti-NAFLD mechanisms have not been fully elucidated. Previous studies have found that flavonoids, as natural substances with extensive pharmacological activity and good therapeutic effects, have excellent antioxidant, anti-inflammatory, metabolic disease improvement, anti-tumor, and other properties and can significantly alleviate NAFLD. Flavonoids could be further developed as therapeutic drugs for NAFLD. In this paper, the pathogenesis of NAFLD and the mechanisms of flavonoids against NAFLD are summarized to provide a theoretical basis for screening flavonoids against non-alcoholic liver injury.

As the secondary fault of the Niushoushan-Luoshan Fault Zone, the Liumugao Fault records the northeastward expansion of the Tibetan Plateau. Based on WorldDEM data, 11 rivers (R1-R11) that flow across the Liumugao Fault and their drainage basins were extracted using ArcGIS technology and a MATLAB script. The longitudinal profiles, Hack profiles, and stream length-gradient (SL) indexes of these rivers, as well as the hypsometric integral (HI) of their drainage basins, were extracted and calculated and combined with field observations to quantitatively analyze the activity of Liumugao Fault. The results show that: (1) the longitudinal profiles of the 11 rivers are steep, the Hack profiles of most rivers drop sharply at the main fault, and the average HI value of the drainage basins is ∼0.4. These phenomena indicate that the current activity of the fault is strong. (2) The average HI values of the drainage basins in the northern, middle, and southern segments of Liumugao Fault are 0.32, 0.37 and 0.45, respectively. Accordingly, the average normalized stream-gradient (SL/K) values of the three segments are 3.72, 4.64 and 7.16, respectively. These data show that the activity of the Liumugao Fault gradually increases from north to south.

With global warming accelerating, polar amplification is one of the hot issues in climate research. However, most studies focus on Arctic amplification, and little attention has been paid to Antarctic amplification (AnA), and there is no relevant research based on MODIS (Moderate Resolution Imaging Spectroradiometer) land surface temperature observations. Compared with 128 stations’ observations, MODIS can capture the variations in temperature over Antarctica. In addition, the temperature changes in Antarctica, East Antarctica, West Antarctica and the Antarctic Peninsula during the period 2001–2018 reflected by the MODIS and ERA5 are basically consistent, and the temperature changes in Antarctica are negatively correlated with the Southern Annular Mode. AnA occurs under all annual and seasonal scales, with an AnA index greater than 1.27 (1.31) from the MODIS (ERA5), and is strongest in the austral winter and weakest in summer. AnA displays regional differences, and the signal from the MODIS is similar to that from ERA5. The strongest amplification occurs in East Antarctica, with an AnA index greater than 1.45 (1.48) from the MODIS (ERA5), followed by West Antarctica, whereas the amplified signal is absent at the Antarctic Peninsula. In addition, seasonal differences can be observed in the sub regions of Antarctica. For West Antarctica, the greatest amplification appears in austral winter, and in austral spring for East Antarctica. The AnA signal also can be captured in daytime and nighttime observations, and the AnA in nighttime observations is stronger than that in daytime. Generally, the MODIS illustrates the appearance of AnA for the period 2001–2018, and the Antarctic climate undergoes drastic changes, and the potential impact should arouse attention.

As essential regulators of mitochondrial quality control, mitochondrial dynamics and mitophagy play key roles in maintenance of metabolic health and cellular homeostasis. Here we show that knockdown of the membrane-inserted scaffolding and structural protein caveolin-1 (Cav-1) and expression of tyrosine 14 phospho-defective Cav-1 mutant (Y14F), as opposed to phospho-mimicking Y14D, altered mitochondrial morphology, and increased mitochondrial matrix mixing, mitochondrial fusion and fission dynamics as well as mitophagy in MDA-MB-231 triple negative breast cancer cells. Further, we found that interaction of Cav-1 with mitochondrial fusion/fission machinery Mitofusin 2 (Mfn2) and Dynamin related protein 1 (Drp1) was enhanced by Y14D mutant indicating Cav-1 Y14 phosphorylation prevented Mfn2 and Drp1 translocation to mitochondria. Moreover, limiting mitochondrial recruitment of Mfn2 diminished formation of the PINK1/Mfn2/Parkin complex required for initiation of mitophagy resulting in accumulation of damaged mitochondria and ROS (mtROS). Thus, these studies indicate that phospho-Cav-1 may be an important switch mechanism in cancer cell survival which could lead to novel strategies for complementing cancer therapies.

As a natural refrigerant, CO2 can greatly improve the environmental protection of the heat pump system. Since there is no perfectly suitable heat transfer correlation for supercritical CO2 at present, the water outlet temperature of the transcritical CO2 heat pump system has not been predicted. To study the applications of transcritical CO2 heat pump systems in heating performance and hot water supply, a series of experiments are carried out by an air source transcritical CO2 heat pump test rig. The experimental results show that the main factors affecting outlet water temperature are the system COP, the discharge pressure, the compressor frequency, and the ambient temperature. Based on the experimental results, a dimensionless correlation equation on outlet water temperature is proposed by the Buckingham PI theorem. This equation can be used to calculate the outlet water temperature of the air source transcritical CO2 heat pump systems with different sizes, and the calculation accuracy can be maintained at 13% with experimental results. Finally, the influence factors of the gas cooler water outlet temperature are analyzed based on the novel calculation method. Therefore, this study provides a reference for the prediction of the water outlet temperature of the transcritical CO2 heat pump system.

Long-term and high-resolution gridded products of precipitation and temperature data are highly important to study the changes in climate and environment under global warming. Considering the uncertainties of these products in mountainous areas, it is necessary to evaluate the data reliability. This study evaluates the performances of the CMFD (China Meteorological Forcing Dataset) and ERA5-Land in simulating precipitation and temperature in the Qilian Mountains over the period of 1980–2018. We use the observation data of 28 basic meteorological stations in the Qilian Mountains to compare with the reanalysis products. Error metrics (the correlation coefficient (CC), the root mean square error (RMSE), the mean absolute error (MAE), and the relative bias (BIAS)) are used to quantify the monthly differences in existence between the observed data and reanalysis data. Our findings indicate that both CMFD and ERA5-Land could well reproduce the spatial distribution of mean monthly precipitation and temperature in the region. A good correlation is found between CMFD and OBS under different amounts of monthly precipitation conditions. The monthly average temperatures of CMFD and ERA5-Land reveal a high correlation with the observed results. Moreover, the CC values of CMFD and ERA5-Land precipitation products are the highest in autumn and the lowest in winter, and the CC values of both CMFD and ERA5-Land temperature products are higher in spring and autumn. However, we find that both reanalysis products underestimate the temperature to varying degrees, and the amount of precipitation is overestimated by ERA5-Land. The results of the evaluation show that the errors in precipitation yielded by CMFD as a whole are distinctly fewer than those yielded by ERA5-Land, while the errors in air temperature yielded by both ERA5-Land and CMFD are nearly identical to each other. Overall, ERA5-Land is more suitable than CMFD for studying the trends of temperature changes in the Qilian Mountains. As for simulation of precipitation, CMFD performs better in the central and eastern parts of the Qilian Mountains, whereas ERA5-Land performs better in the western part of the Qilian Mountains.

In the primary analysis of the phase III COLUMBA study, daratumumab by subcutaneous administration (DARA SC) demonstrated non-inferiority to intravenous administration (DARA IV) for relapsed or refractory multiple myeloma (RRMM). Here, we report the final analysis of efficacy and safety from COLUMBA after a median of 29.3 months follow-up (additional 21.8 months after the primary analysis). In total, 522 patients were randomized (DARA SC, n=263; DARA IV, n=259). With longer follow-up, DARA SC and DARA IV continued to show consistent efficacy and maximum trough daratumumab concentration as compared with the primary analysis. The overall response rate was 43.7% for DARA SC and 39.8% for DARA IV. The maximum mean (standard deviation [SD]) trough concentration (cycle 3, day 1 pre-dose) of serum DARA was 581 (SD, 315) μg/mL for DARA SC and 496 (SD, 231) μg/mL for DARA IV. Median progression-free survival was 5.6 months for DARA SC and 6.1 months for DARA IV; median overall survival was 28.2 months and 25.6 months, respectively. Grade 3/4 treatment-emergent adverse events occurred in 50.8% of patients in the DARA SC group and 52.7% in the DARA IV group; the most common (≥10%) were thrombocytopenia (DARA SC, 14.2%; DARA IV, 13.6%), anemia (13.8%; 15.1%), and neutropenia (13.1%; 7.8%). The safety profile remained consistent with the primary analysis after longer follow-up. In summary, DARA SC and DARA IV continue to demonstrate similar efficacy and safety, with a low rate of infusion-related reactions (12.7% vs. 34.5%, respectively) and shorter administration time (3-5 minutes vs. 3-7 hours) supporting DARA SC as a preferable therapeutic choice. (Clinicaltrials gov. Identifier: NCT03277105.

Therapeutic approaches of combining conventional photodynamic therapy (PDT) with other adjuvant treatments to sensitize PDT represent an appealing strategy. Herein, a novel synergetic “nanobomb” strategy based on glutathione (GSH)-responsive biodegradation was proposed to effectively destroy tumors expeditiously and accurately. This “nanobomb” was rationally constructed via the simultaneous encapsulation of methylene blue (MB) and l-arginine (L-Arg) into polyethylene glycol (PEG) modified mesoporous organosilicon nanoparticles (MON). The resulting L-Arg/MB@MP initially exhibited prolonged blood circulation, improved bioavailability, and enhanced tumor accumulation in mice after tail vein injection according to the pharmacokinetic investigations, before the nanoparticles were entirely excreted. Under laser irradiation, L-Arg/MB@MP produced remarkable reactive oxygen species (ROS) directly for PDT therapy, while a portion of ROS may oxidize L-Arg to generate nitric oxide (NO) not only for gas therapy (GT) but also serve as a biological messenger to regulate vasodilation to alleviate the tumor hypoxia. Subsequently, the rapidly released NO was further oxidized to reactive nitrogen species, which together with ROS promote immunogenic cell death by inducing G2/M cell-cycle arrest and apoptosis in cancer cells, and eventually resulting in enhanced anti-tumor immune responses. Moreover, the GSH depletion in tumor tissues induced by L-Arg/MB@MP biodegradation can cooperate with GT to amplify the therapeutic effect of PDT. These results demonstrate that this “nanobomb” provides new ideas for clinical translation to treat tumor patients in terms of synergistic PDT-GT nanotherapy in hypoxic-solid tumors.

As the largest valley glacier in the Qilian Mountains, the Laohugou glacier No. 12 (LHG12) has shrunk significantly since 1957. In this study, two topographic maps and a WorldView-2 satellite stereopair image data were used to assess the volume and cumulative mass balance of LHG12 located at the western Qilian Mountains during 1957–2015. During the study period, the LHG12 exhibited changes in two processes: slightly ablation and stability in a brief period during 1957–1989 and strong melting and accelerated ablation during 1989–2015. During 1957–2015, the volume of LHG12 decreased by 0.38 km3, the average thickness decreased by 17.23 m, the cumulative mass balance (MB) was −14.69 ± 3.00 m w. e., and ablation was found glacier-wide. By comparing the previous MB simulation and digital elevation model (DEM) differencing results, it was found that the MB simulation results underestimated the strong melting trend of LHG12 since the 1990s. Temperature rose, especially in autumn and winter, and could cause the ice temperature of LHG12 to increase, and LHG12 may become more sensitive to climate change.

Accurate estimates of albedo can be crucial for energy balance models of glaciers. A number of algorithms exist which are often site dependent and rely on accurate measurements or estimates of snow depth. Using the well-established COSIMA model we simulate the energy and mass balance of the Laohugou Glacier No.12 in the Qilian Mountains, on the northern fringe of the Qinghai-Tibetan Plateau, a glacier that has been well studied in the past. Using energy flux and mass balance measurements between 2010 and 2015 we were able to validate the model over multiple seasons. Using the original albedo parametrization, the model fails to reproduce the observed mass balance. We show that this is due to the failure to estimate snow depth accurately. We therefore applied two alternative albedo algorithms, one well established example and one new parametrization only dependent on temperature and time since last snow fall. As a result, mass balance simulations improve considerably from a RMSE of 0.53 m w.e. for the original parametrization to 0.39 and 0.19 m w.e. for the uncalibrated established and the new calibrated model respectively. Modelled albedo during the ablation period (NSE = 0.05, R2 = 0.33) is more accurate than during the accumulation period (NSE = −0.37, R2 = 0.04). Testing the new model at another glacier on the Tibetan Plateau shows that a local recalibration of parameters remains necessary to achieve satisfying results. Investigations into the effect of impurities in snow, regional moisture sources and changing surface characteristics with rising temperatures will be crucial for accurate projections into the future.

During development, organs undergo large scale forces driven by the cytoskeleton but the precise molecular regulation of cytoskeletal networks remains unclear. Here, the authors report a Cdc42-dependent supracellular cytoskeletal network integrates local actomyosin contraction at tissue scale and drives global tissue elongation.

Polar amplification has been a research focus in climate research in recent decades. However, little attention has been paid to Antarctic amplification (AnA). We have examined the variations in annual and seasonal temperature over the Antarctic Ice Sheet and its amplification based on reconstruction covering the period 2002–2018. The results show the occurrence of annual and seasonal AnA, with an AnA index greater than 1.39 with seasonal differences, and that AnA is strong in the austral winter and spring. Moreover, AnA displays regional differences, with the greatest amplification occurring in East Antarctica, with an AnA index greater than 1.51, followed by West Antarctica. AnA is always absent in the Antarctic Peninsula. In addition, amplification in East Antarctica is most conspicuous in spring, which corresponds to the obvious warming in this season; and the spring amplification signal is weakest for West Antarctica. When considering the influence of the ocean, the AnA becomes obvious, compared to when only the land is considered. Southern Annular Mode (SAM), surface pressure and westerlies work together to affect the temperature change over Antarctica and AnA; and SAM and surface pressure are highly correlated with the temperature change over East Antarctica. The picture reflects the accelerated changes in Antarctic temperature.

ABSTRACT Distinct but related species of elephant endotheliotropic herpesviruses (EEHVs) circulate within Asian and African elephant populations. Primary infection with EEHVs endemic among Asian elephants can cause clinical illness and lethal EEHV hemorrhagic disease (EEHV-HD). The degree to which this occurs among African elephants has not been fully established. Recent cases of EEHV-HD caused by the EEHV3 species in African elephants housed in North American zoos has heightened concern about the susceptibility of this elephant species to EEHV-HD. In this study, we utilize the luciferase immunoprecipitation system (LIPS) to generate a serological assay specific for EEHV3 in African elephants by detecting antibodies against the EEHV3 E34 protein. The results showed that the majority of tested elephants from four separate and genetically unrelated herds, including five elephants that survived clinical illness associated with EEHV3, were positive for prior infection with EEHV3. However, African elephants who succumbed to EEHV3-HD were seronegative for EEHV3 prior to lethal infection. This supports the hypothesis that fatal EEHV-HD caused by EEHV3 is associated with primary infection rather than reactivation of latent virus. Lastly, we observed that African elephants, like Asian elephants, acquire abundant anti-EEHV antibodies prenatally and that anti-EEHV3 specific antibodies were either never detected or declined to undetectable levels in those animals that died from lethal disease following EEHV3 infection. IMPORTANCE Prior to 2019, only five cases of clinical disease from EEHV infection among African elephants had been documented. Since 2019, there have been at least seven EEHV-HD cases in North American zoos, resulting in three fatalities, all associated with EEHV3. Evidence is accumulating to suggest that EEHV-associated clinical illness and death among Asian elephants is due to primary infection and may be associated with waning anti-EEHV antibody levels in young elephants. The development of the EEHV3 serological test described in this study enabled us to confirm that similar dynamics may be contributing to EEHV-HD in African elephants. The ability to screen for EEHV immune status in African elephant calves will have a major impact on managing captive African elephant herds and will provide new tools for investigating and understanding EEHV in wild populations.

Laohugou Glacier No. 12 is located on the northern slope of the western Qilian Mountains with a temperate continental wet climate and an extremely cold winter. Bacteria in a newly exposed moraine have to cope with various pressures owing to deglaciation at the glacier snout. However, limited information is available regarding the high diversity and temporary survival of culturable heterotrophic bacteria under various environmental stresses. To examine the tolerance of extremophiles against varying environmental conditions in a newly exposed moraine, we simulated environmental stress in bacterial cultures. The results showed that the isolated strains belonged to actinobacteria, Proteobacteria, Bacteroidetes, Deinococcus-Thermus, and Firmicutes. Actinobacteria was the most abundant phylum, followed by Proteobacteria, at both high and low temperatures. Pseudarthrobacter was the most abundant genus, accounting for 14.2% of the total isolates. Although several microorganisms grew at 10 °C, the proportion of microorganisms that grew at 25 °C was substantially higher. In particular, 50% of all bacterial isolates grew only at a high temperature (HT), whereas 21.4% of the isolates grew at a low temperature (LT), and 38.6% of the isolates grew at both HT and LT. In addition, many radiation-resistant extremophiles were identified, which adapted to both cold and oxidative conditions. The nearest neighbors of approximately >90% of bacteria belonged to a nonglacial environment, such as oil-contaminated soil, rocks, and black sand, instead of glacial niches. This study provides insights into the ecological traits, stress responses, and temporary survival of culturable heterotrophic bacteria in a newly exposed moraine with variable environmental conditions and the relationship of these communities with the non-glacial environment. This study may help to understand the evolution, competition, and selective growth of bacteria in the transition regions between glaciers and retreats in the context of glacier melting and retreat owing to global warming.

A long-series mass balance (MB) of glaciers can be used to study glacier–climate relationships. Using a distributed simplified energy balance model (SEBM) and an enhanced temperature-index model (ETIM), the MB of Laohugou Glacier No. 12 (LHG12) was reconstructed from 1980 to 2020, driven by a calibrated ERA5 reanalysis dataset. The simulation of SEBM performs better than that of ETIM. The results showed that the annual MB of LGH12 is a fluctuating trend of declining from 1980 to 2020, with annual means of −0.39 ± 0.28 m w.e. a−1 and cumulative value of −16 ± 4 m w.e. During 1980–1990, the annual MB fluctuated in a small range, while after 1990, LHG12 accelerated melting owing to rising air temperature, with annual means of −0.48 m w.e. a−1, three times as large as that of 1980–1990. The largest mass loss occurred during 2001–2010 at an average rate of −0.57 m w.e. a−1. The average equilibrium line altitude (ELA) was 4976 m a.s.l., and since 1980, the ELA has been increasing at a rate of 37.5 m/10 a. LHG12 is most sensitive to air temperature, and the MB sensitivity reaches −0.51 m w.e. a−1 with air temperature increase of 1 °C. The sensitivity of MB to incoming shortwave radiation (+10%) simulated by SEBM is −0.30 m w.e. a−1, three times larger than that simulated by ETIM. This is mainly because the two models have different conditions for controlling melting. Melting is controlled only by air temperature for ETIM, while for SEBM, it is controlled by air temperature and incoming shortwave radiation.

The current wastewater treatment method shows low efficiency in treating wastewater with high concentrations of chemical mechanical pulp (CMP). Therefore, a chlorine dioxide Pretreatment Anaerobic Treatment (DPAT) was developed and applied to treat the CMP wastewater to obtain higher efficiency, obtaining the following results: The biodegradability of CMP wastewater improved after chlorine dioxide pretreatment. The COD of wastewater treated with chlorine dioxide was reduced from 5634 mg/L to 660 mg/L. The removal rate for chemical oxygen demand (COD) was 88.29%, 29.13% higher than the common anaerobic treatment. The reasons for the high efficiency of the DPAT treatment were that chlorine dioxide pretreatment removed the toxic substances in the original wastewater and thereby promoted the proliferation and growth of the anaerobe. The results show that pretreatment with chlorine dioxide can effectively enhance the biodegradability of high-concentration CMP wastewater. Therefore, DPAT treatment of high-concentration CMP wastewater is beneficial to environmental protection.

The prevention of metastasis is a central goal of cancer therapy. Caveolin-1 (Cav-1) is a structural membrane and scaffolding protein shown to be a key regulator of late-stage breast cancer metastasis. However, therapeutic strategies targeting Cav-1 are still lacking. Here, we demonstrate that the pharmacological activation of potassium channel Kv11.1, which is uniquely expressed in MDA-MB-231 triple negative breast cancer cells (TNBCs) but not in normal MCF-10A cells, induces the dephosphorylation of Cav-1 Tyr-14 by promoting the Ca2+-dependent stimulation of protein tyrosine phosphatase 1B (PTP1B). Consequently, the dephosphorylation of Cav-1 resulted in its disassociation from β-catenin, which enabled the accumulation of β-catenin at cell borders, where it facilitated the formation of cell–cell adhesion complexes via interactions with R-cadherin and desmosomal proteins. Kv11.1 activation-dependent Cav-1 dephosphorylation induced with NS1643 also reduced cell migration and invasion, consistent with its ability to regulate focal adhesion dynamics. Thus, this study sheds light on a novel pharmacological mechanism of promoting Cav-1 dephosphorylation, which may prove to be effective at reducing metastasis and promoting contact inhibition.

Cryoconite is a dark-coloured granular sediment that contains biological and mineralogical components, and it plays a pivotal role in geochemistry, carbon cycling and glacier mass balance. In this work, we collected cryoconite samples from Laohugou Glacier No. 12 (LHG) on the north-eastern Tibetan Plateau during the summer of 2015 and measured the spectral albedo. To explore the impacts of this sediment on surface ablation, the ice melting differences between the cryoconite-free (removed) ice and the intact layers were compared. The results showed that the mean concentrations of black carbon (BC), organic carbon (OC) and total iron (Fe) in the LHG cryoconite were 1.28, 11.18 and 39.94 mg g−1, respectively. BC was found to play a stronger role in solar light adsorption than OC and free Fe. In addition, ice covered by cryoconite exhibited the lowest mean reflectance (i.e.,

Laohugou glacier No. 12 (LHG12), located in the northeast of the Qinghai–Tibet Plateau, is the largest valley glacier in the Qilian mountains. Since 1957, LHG12 has shrunk significantly. Due to the limitations of in situ observations, simulations and investigations of LHG12 have higher levels of uncertainty. In this study, consumer-level, low-altitude microdrones were used to conduct repeated photogrammetry at the lower part of LHG12, and a digital orthophoto map (DOM) and a digital surface model (DSM) with a resolution at the centimeter scale were generated, from 2017 to 2021. The dynamic parameters of the glacier were detected by artificial and automatic extraction methods. Using a combination of GNSS and drone-based data, the dynamic process of LHG12 was analyzed. The results show that the terminus of LHG12 has retreated by 194.35 m in total and by 19.44 m a−1 on average during 2008–2021. The differential ablation leading to terminus retreat distance markedly increased during the study period. In 2019–2021, the maximum annual surface velocity was 6.50 cm day−1, and during ablation season, the maximum surface velocity was 13.59 cm day−1, 52.17% higher than it is annually. The surface parameters, motion, and mass balance characteristics of the glacier had significant differences between the west and east branches. The movement in the west branch is faster than it is in the east branch. Because of the extrusion of the two ice flows, there is a region with a faster surface velocity at the ablation area. The ice thickness of LHG12 is decreasing due to intensified ablation, leading to a deceleration in the surface velocity. In large glaciers, this phenomenon is more obvious than it is in small glaciers in the Qilian mountains.

Linking snow cover frequency (SCF) and atmospheric circulation is vital for comprehension of hemispheric-scale change mechanisms and for accurate forecasting. This study combined MODIS imagery with meteorological observations to investigate the variation of annual SCFs in the Qilian Mountains. Results indicated that more than 80% of annual SCF is distributed at high elevations and mostly on northern slopes, and that SCF is greater in the west than in the east. Abrupt change in the increase in annual SCF was not detected; however, significant (0.05 confidence level) variation with quasi-3-year and quasi-5-year periods indicated potential connection with monsoons. Topographically, SCF increased at high elevations and decreased in valleys. Moreover, SCF increased significantly with a rise in slope below 23° and then decreased between 23° and 45°, and it decreased with a change in aspect from 70° to 200° and then increased from 200° to 310°. Annual SCF variation in the Qilian Mountains is dominated by precipitation rather than by temperature. In the years with high SCFs, southeasterly winds associated with an anticyclone over southeastern China and southwesterly winds associated with the cyclone over the Iranian Plateau brought warm moisture across northwestern China, favoring snowfall in the Qilian Mountains. Meanwhile, cold moisture outbreaks from the Arctic into the mid-latitudes are conducive to maintaining snow cover. However, in the years with low SCFs, the cold air might be difficultly transporting out of the Arctic region due to the strengthening polar vortex. Moreover, the water vapor was less than that of the mean state and divergence over the Qilian Mountains, which difficultly conduced snowfall over the Qilian Mountains.