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SUMMARYStrain partitioning between strike-slip faults in mountains and thrust faults in the foreland is a typical mountain building process to accommodate oblique plate convergence. Studying the geometry and movement of such strain-partitioned fault systems is key to understanding the mountain building process and related seismic hazards. The 2022 Mw 6.6 Menyuan earthquake is the largest strike-slip earthquake to have ruptured the northern Qilian Shan fault system in the modern geodetic era. We combined satellite and field observations to determine the fault geometry and coseismic slip distribution in the Menyuan earthquake, and link the distribution of coseismic slip with the pattern of interseismic strain accumulation within the northern Qilian Shan from our geodetic slip model. We find that the Menyuan earthquake ruptured a 25 km-long section of the left-lateral Longlongling Fault between the surface and 7 km depth. The maximum slip was 4 m at 3–4 km depth. Damage to a high-speed railway tunnel recorded a fault offset of 2.7 m at a depth of 200 m compared to 2.5–3.0 m on the surface, suggesting that dispersion of the rupture through unconsolidated shallow sediments was limited, at least at the tunnel site. We also determined the pattern of interseismic deformation prior to the earthquake using Interferometric Synthetic Aperture Radar and Global Navigation Satellite System data. We found the interseismic geodetic data can be explained by the oblique movement of a low-angle décollement beneath the Qilian Shan rather than a strain partitioning fault system. We suggested that the strike-slip faults and foreland thrusts are separated by a creeping décollement, which would act as a barrier to stop the cascading rupture of the strike-slip and thrust fault.

Background Therapeutic monoclonal antibodies targeting complement C5 have proven to be a very effective approach for the treatment of complement-associated diseases including paroxysmal nocturnal hemoglobinuria (PNH). However, C5 antibody alone often cannot sufficiently block the alternative pathway (AP) of the complement system, nor reduce the deposition of C3b on the cell surface produced by C3 activation, and even increase the deposition, which is considered to be the cause of extravascular hemolysis in PNH patients treated with C5 antibody. As a natural and powerful complement inhibitor, CR1 has potential for drug development, but shows poor druggability due to low yield, short PK etc. Here, by fusing different CR1 fragments with the C5 antibody, we tried to obtain a fusion protein with good yield, purity and activity. Methods Candidate fusion proteins were generated by transient transfection expression and purified via Protein A affinity chromatography. Their bioactivities were investigated by in vitro classical pathway (CP)- and AP-mediated hemolysis assays. C3b deposition was calculated by flow cytometry. The PK/PD characteristics of optimized fusion proteins were tested in wildtype and human C5 transgenic mice, as well as cynomolgus monkeys. The therapeutic effect of the final product for complement-associated diseases was examined in collage antibody induced arthritis (CAIA) model mice. Results By fusing the mutated short consensus repeat (SCR) 1–5 fragment of CR1 to N-terminal of the heavy chain of C5 antibody, modifying surface charge and attaching linkers, we finally obtained a bifunctional complement inhibitory fusion protein with higher yield and superior CP and AP inhibitory activities. It showed a capability to inhibit C3 fragment deposition and therapeutic potential for CAIA, with one-week in vivo sustained bioactivity. Conclusions The fusion protein has the potential to become a more comprehensive complement activity-inhibiting drug, which may overcome the inefficiency of C5 antibody therapy.

The Western Qinling orogenic belt (WQOB) is one of the most important prospective gold districts in China, with widely distributed Indosinian intermediate–acidic intrusions. The Liziyuan Au deposit is a representative orogenic deposit in the northern WQOB, hosting several sections spatially associated with igneous rocks. The Au deposit is hosted by meta-sedimentary volcanic rocks of the Cambrian–Ordovician Liziyuan Group and the Tianzishan monzogranite. Two periods, including five stages of mineralization, are recognized in this area: an early metamorphic mineralization period (PI), including quartz–pyrite (Stage I) and banded quartz–polymetallic sulfide (Stage II) veins, and a later magmatic mineralization period (PII) including quartz–K-feldspar–pyrite–molybdenite veins (Stage III), quartz–polymetallic sulfide–chlorite ± calcite veinlets and stockwork (Stage IV), and late calcite–quartz veinlets (Stage V). Geochronological studies indicate a SHRIMP zircon U-Pb age of 236.1 Ma for the Tianzishan monzogranite, and our published ages of ore-bearing diorite porphyrite of the Suishizi section and granite porphyry of the Jiancaowan section being 213 and 212 Ma, respectively. Pyrites formed in association with PI and PII mineralization have well-defined Rb–Sr ages of 220 ± 7.5, 205.8 ± 8.7, and 199 ± 15 Ma, with close temporospatial coupling between mineralization and magmatism. The δ18O and δD values of fluid inclusions in Stage IV auriferous quartz veins range from −0.03‰ to +5.24‰ and −93‰ to −75‰, respectively, suggesting that mineralizing fluid was likely of magmatic origin. Three distinct ranges of δ34S values are identified in the studied sections (i.e., 7.04‰–9.12‰, −4.95‰ to −2.44‰, and 0.10‰–3.08‰), indicating a source containing multiple sulfur isotopes derived from magmatic and metamorphic fluids. The Liziyuan Au deposit is thus likely an orogenic deposit closely related to magmatism. Geochemical characteristics indicate that Tianzishan monzogranite is adakitic and was derived from thickened lower crust during Triassic orogenesis. The ore-bearing diorite porphyrite and granite porphyry formed in a post-collision extensional setting. Together with previous geological and geochemical data, our results indicate that the Liziyuan orogenic Au deposit was formed by early collisional–compressional metamorphism and late post-collision extensional magmatic fluids related to the evolution of the WQOB.

Objective: To observe the clinical effect of modified Yu Rong San gel eye mask in the treatment of dark circles. Methods: 96 cases of patients with dark circles were randomly divided into treatment group and control group. In the control group and the treatment group, the common eye mask and the modified Yu Rong San gel eye mask were applied to the black circle area respectively. After 15min, water was used to wash the face, the application of the mask for one time a day, four weeks, one course, and three courses were observed. Results: After three courses of treatment, the total effective rate of the treatment group was higher than that of the control group (P

Aims Woody plants are widely distributed in various grassland types along the altitudinal/climatic gradients in Xinjiang, China. Considering previously reported change in carbon (C) storage following woody plant encroachment in grasslands and the mediating effect of climate on this change, we predicted that a positive effect of woody plants on plant C storage in semiarid grasslands may revert to a negative effect in arid grasslands. We first investigated the spatial variation of aboveground C (AGC) and belowground C (BGC) storage among grassland types and then tested our prediction. Methods We measured the living AGC storage, litter C (LC) and BGC storage of plants in two physiognomic types, wooded grasslands (aboveground biomass of woody plants at least 50%) and pure grasslands without woody plants in six grassland types representing a gradient form semiarid to arid conditions across Xinjiang. Important Findings Living AGC, LC, BGC and total plant C storage increased from desert to mountain meadows. These increases could also be explained by increasing mean annual precipitation (MAP) or decreasing mean annual temperature (MAT), suggesting that grassland types indeed represented an aridity gradient. Woody plants had an effect on the plant C storage both in size and in distribution relative to pure grasslands. The direction and strength of the effect of woody plants varied with grassland types due to the mediating effect of the climate, with wetter conditions promoting a positive effect of woody plants. Woody plants increased vegetation-level AGC through their high AGC relative to herbaceous plants. However, more negative effects of woody plants on herbaceous plants with increasing aridity led to a weaker increase in the living AGC in arid desert, steppe desert and desert steppe than in the less arid other grassland types. Under greater aridity (lower MAP and higher MAT), woody plants allocated less biomass to roots and had lower BGC and had a more negative impact on herbaceous plant production, thereby reducing vegetation-level BGC in the desert, steppe desert and desert steppe. In sum, this resulted in a negative effect of woody plants on total plant C storage in the most arid grasslands in Xinjiang. As a consequence, we predict that woody plant encroachment may decrease rather than increase C storage in grasslands under future drier conditions.

Colon and rectal cancers are the leading causes of cancer-related deaths in the United States and effective targeted therapies are in need for treating them. Our genomic analyses show hemizygous deletion of TP53, an important tumor suppressor gene, is highly frequent in both cancers, and the 5-year survival of patients with the more prevalent colon cancer is significantly reduced in the patients with the cancer harboring such deletion, although such reduction is not observed for rectal cancer. Unfortunately, direct targeting TP53 has been unsuccessful for cancer therapy. Interestingly, POLR2A, a gene essential for cell survival and proliferation, is almost always deleted together with TP53 in colon and rectal cancers. Therefore, RNA interference (RNAi) with small interfering RNAs (siRNAs) to precisely target/inhibit POLR2A may be an effective strategy for selectively killing cancer cells with TP53 deficiency. However, the difficulty of delivering siRNAs specifically into the cytosol where they perform their function, is a major barrier for siRNA-based therapies. Here, metformin bicarbonate (MetC) is synthesized to develop pH-responsive MetC-nanoparticles with a unique “bomb” for effective cytosolic delivery of POLR2A siRNA, which greatly facilitates its endo/lysosomal escape into the cytosol and augments its therapeutic efficacy of cancer harboring TP53 deficiency. Moreover, the MetC-based nanoparticles without functional siRNA show notable therapeutic effect with no evident toxicity or immunogenicity.

Aims We have found a positive effect of woody plants on total plant carbon (C) storage in less arid grassland was shifted to a negative effect in arid grasslands in Xinjiang, a typical arid region in China. In this study, we further assessed the effects of woody plants on aboveground primary productivity (ANPP) and soil organic C (SOC) storage and explored the mediation of climate conditions on these effects. We also aimed to elucidate the reasons for the effects on SOC storage in terms of ANPP and belowground biomass C (BGC). Methods We compared the difference in ANPP and SOC content between pure and wooded grasslands and evaluated the relation between SOC content and ANPP and BGC in six grassland types along the altitude (climatic) gradients. Results In three arid types, woody plants had a negative effect on ANPP due to their more negative impacts on herbaceous plants and lower ANPP. The negative effect on ANPP and BGC led to that on SOC storage in these types. In less arid types, there had a positive effect on ANPP because woody plants had weaker negative impacts on herbaceous plants and higher ANPP. A positive effect on ANPP combined with a neutral impact on BGC contributed to a positive effect on SOC storage in these types. Conclusions Woody plants had a negative effect on ANPP and SOC storage in most arid grasslands in Xinjiang. We predicted that increasing aridity may reduce ANPP and SOC storage with woody plant encroachment in the future.

A simple and efficient biphasic system consisting of H2O, tetrahydrofuran (THF), cyclohexane (CHX) and Al2(SO4)3 was employed to convert cellulose into 5-hydroxymethylfurfural (HMF) with high yield of 71.2%. The real volumes of organic phase (Vorg) and aqueous phase (Vaque) of the biphasic system at reaction temperature were measured to found out that over 80% of the added H2O was dissolved into the organic phase at reaction temperature, leading to high Vorg/Vaque (over 44/1) and high concentration of Al2(SO4)3 (over 0.34 g/mL) in aqueous phase. The high concentration of Al2(SO4)3 in aqueous phase could efficiently catalyze the conversion of cellulose into HMF, while the high Vorg/Vaque could protect the formed HMF from rehydration, all of which are responsible for the high efficiency of the system on conversion of cellulose into HMF. The addition of CHX into reaction mixture could decrease the solubility of Al2(SO4)3 and H2O in the organic phase, which could improve the stability of HMF in the reaction system, resulting higher yield of HMF from cellulose. Because of the high Vorg/Vaque of the reaction system, one microemulsion-like system and liquid film catalytic model are proposed for the cellulose-to-HMF process.

The association between biodiversity and belowground biomass (BGB) remains a central debate in ecology. In this study, we compared the variations in species richness (SR) and BGB as well as their interaction in the top (0–20 cm), middle (20–50 cm) and deep (50–100 cm) soil depths among 8 grassland types (lowland meadow, temperate desert, temperate desert steppe, temperate steppe desert, temperate steppe, temperate meadow steppe, mountain meadow and alpine steppe) and along environmental gradients (elevation, energy condition (annual mean temperature (AMT) and potential evapotranspiration (PET)), and mean annual precipitation (MAP)) based on a 2011–2013 survey of 379 sites in Xinjiang, Northwest China. The SR and BGB varied among the grassland types. The alpine steppe had a medium level of SR but the highest BGB in the top soil depth, whereas the lowland meadow had the lowest SR but the highest BGB in the middle and deep soil depths. The SR and BGB in the different soil depths were tightly associated with elevation, MAP and energy condition; however, the particular forms of trends in SR and BGB depended on environmental factors and soil depths. The relationship between SR and BGB was unimodal in the top soil depth, but SR was positively related with BGB in the middle soil depth. Although elevation, MAP, energy condition and SR had significant effects on BGB, the variations in BGB in the top soil depth were mostly determined by elevation, and those in the middle and deep soil depths were mainly affected by energy condition. These findings highlight the importance of environmental factors in the regulations of SR and BGB as well as their interaction in the grasslands in Xinjiang.

Phytic acid derived carbons provide an excellent dual functionality for lithium- and sodium-ion batteries under tuned pyrolysis temperature. The acquired carbon at 800 °C is suitable to lithium-ion batteries due to its high surface area (1426.75 m2 g−1) and hierarchical porous structure. Tested against Li, it delivers a high capacity of 1787 mA h g−1 and coulombic efficiency of 82%. Another obtained carbon at 950 °C is suitable to sodium-ion batteries due to its large lattice spacing (0.4115 nm), defect density and phosphorus content (1.12%). Tested against Na, it delivers the initial specific capacity of 387 mA h g−1 with coulombic efficiency of 50.6%, and maintains a high reversible capacity of 300 mA h g−1 after 300 cycles at a current rate of 100 mA g−1. High energy density and power density are also acquired in lithium- and sodium-ion batteries. The effects of pyrolysis temperature on microstructure and electrochemical behaviours of carbons are discussed detailedly. It is proved that the carbons with tuned pyrolysis temperature behave differently due to a synergistic effect among the lattice spacing, graphitization degree, defect density, phosphorus concentration and porous structure.

TP53 is the most frequently mutated or deleted gene in triple negative breast cancer (TNBC). Both the loss of TP53 and the lack of targeted therapy are significantly correlated with poor clinical outcomes, making TNBC the only type of breast cancer that has no approved targeted therapies. Through in silico analysis, we identified POLR2A in the TP53-neighboring region as a collateral vulnerability target in TNBC tumours, suggesting that its inhibition via small interfering RNA (siRNA) may be an amenable approach for TNBC targeted treatment. To enhance bioavailability and improve endo/lysosomal escape of siRNA, we designed pH-activated nanoparticles for augmented cytosolic delivery of POLR2A siRNA (siPol2). Suppression of POLR2A expression with the siPol2-laden nanoparticles (siPol2@NPs) leads to enhanced growth reduction of tumours characterised by hemizygous POLR2A loss. These results demonstrate the potential of the pH-responsive nanoparticle and the precise POLR2A targeted therapy in TNBC harbouring the common TP53 genomic alteration.

Bacteria plays a crucial role in soil biogeochemical cycles, bacterial elevational patterns have been well studies over the past decade, but the elevational pattern and its driver poorly understood. To determine the distribution patterns of bacterial composition and diversity across narrow– and broad–scale elevational gradients, we collected soil samples from 22 sites in the grasslands of Mt. Tianshan along three elevational transects and the whole elevation transect: (1) 6 sites at 1047 m – 1587 m, (2) 8 sites at 876 m – 3070 m, and (3) 8 sites at 1602 m – 2110 m. We found a hump pattern of the bacterial community diversity on the whole elevation transect, while not have observed consistent patterns in separately elevation transect. Bacterial community composition based on phylum differed with transects and elevation sites. Furthermore, heatmap analysis showed that pH and MAT significantly (P

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 12 pre-microRNAs (pre-miRNAs). Current studies have shown that these miRNAs are involved in regulation of viral and host gene expression, implicating a role in the maintenance of viral latency and suppression of antiviral innate immunity. However, the functions of these miRNAs remain largely unknown. On the basis of the sequence homology between oncogenic miR-155 and KSHV-encoded miR-K12-11, we hypothesized that miR-K12-11 could attenuate transforming growth factor β (TGF-β) signaling, facilitating viral infection and tumorigenesis. In the present study, we demonstrated that ectopic expression of miR-K12-11 in Ramos, a TGF-β-sensitive cell line, downregulated TGF-β signaling and facilitated cell proliferation upon TGF-β treatment by directly targeting SMAD5, an important mediator in TGF-β signaling. In addition, the downregulation of SMAD5 by miR-K12-11 was further confirmed in a de novo KSHV infection system or latently infected KSHV-positive B-lymphoma cell lines. More importantly, repression of miR-K12-11 by a specific sponge inhibitor restored the expression of SMAD5 in both de novo-infected and latently infected cells. Finally, we found that restoration of SMAD5, in addition to the TGF-β type II receptor, which was epigenetically silenced by the latent viral protein latency-associated nuclear antigen, sensitized BC3 cells to the cytostatic effect of TGF-β signaling. Taken together, our findings highlight a novel mechanism in which miR-K12-11 downregulates TGF-β signaling and suggest that viral miRNAs and proteins may exert a dichotomy regulation in virus-induced oncogenesis by targeting the same signaling pathway.

Cystic fibrosis (CF) is a chronic disease causing severe impairment to the respiratory system and digestive tracts. Currently, CF is incurable. As an autosomal recessive disorder, the morbidity of CF is significantly higher among Caucasians of European descent, whereas it is less pervasive among African and Asian populations. The disease is caused by identical mutations (homozygosity) or different mutations (heterozygosity) of an autosomal recessive mutation at position 7q31.2‑q31.1 of chromosome 7. Diagnostic criteria and guidelines work concurrently with laboratory detection to facilitate precise CF detection. With technological advances, the understanding of CF pathogenesis has reached an unprecedented level, allowing for increasingly precise carrier screening, more effective early stage CF intervention and improved prognostic outcomes. These advances significantly increase the life quality and expectancy of patients with CF. Given the numerous improvements in the field of CF, the current review summarized the technical advances in the study of the molecular mechanisms underlying CF, as well as how these improvements facilitate the clinical outcomes of CF. Furthermore, challenges and obstacles to overcome are discussed.

Chromosome 17q23 amplification occurs in ~11% of human breast cancers. Enriched in HER2+ breast cancers, the 17q23 amplification is significantly correlated with poor clinical outcomes. In addition to the previously identified oncogene WIP1, we uncover an oncogenic microRNA gene, MIR21, in a majority of the WIP1-containing 17q23 amplicons. The 17q23 amplification results in aberrant expression of WIP1 and miR-21, which not only promotes breast tumorigenesis, but also leads to resistance to anti-HER2 therapies. Inhibiting WIP1 and miR-21 selectively inhibits the proliferation, survival and tumorigenic potential of the HER2+ breast cancer cells harboring 17q23 amplification. To overcome the resistance of trastuzumab-based therapies in vivo, we develop pH-sensitive nanoparticles for specific co-delivery of the WIP1 and miR-21 inhibitors into HER2+ breast tumors, leading to a profound reduction of tumor growth. These results demonstrate the great potential of the combined treatment of WIP1 and miR-21 inhibitors for the trastuzumab-resistant HER2+ breast cancers., The 17q23 amplicon containing the WIP1 oncogene is frequently amplified in HER2+ breast cancer. Here they find MIR21 to be present in WIP1-containing amplicons, and report nanoparticle based co-delivery of WIP1 and miR-21 inhibitors to be effective in trastuzumab-resistant HER2+ breast cancer.

Heterozygous deletion of chromosome 17p (17p) is one of the most frequent genomic events in human cancers. Beyond the tumor suppressor TP53, the POLR2A gene encoding the catalytic subunit of RNA polymerase II (RNAP2) is also included in a ~20-megabase deletion region of 17p in 63% of metastatic castration-resistant prostate cancer (CRPC). Using a focused CRISPR-Cas9 screen, we discovered that heterozygous loss of 17p confers a selective dependence of CRPC cells on the ubiquitin E3 ligase Ring-Box 1 (RBX1). RBX1 activates POLR2A by the K63-linked ubiquitination and thus elevates the RNAP2-mediated mRNA synthesis. Combined inhibition of RNAP2 and RBX1 profoundly suppress the growth of CRPC in a synergistic manner, which potentiates the therapeutic effectivity of the RNAP2 inhibitor, α-amanitin-based antibody drug conjugate (ADC). Given the limited therapeutic options for CRPC, our findings identify RBX1 as a potentially therapeutic target for treating human CRPC harboring heterozygous deletion of 17p., Heterozygous loss of chromosome 17p is a common genomic event in castration-resistant prostate cancers (CRPC). Here, the authors use CRISPR-based screen to identify RBX1 as a target gene for CRPC with 17p loss and targeting RBX1 sensitizes CRPC to the treatment of α-amanitin antibody conjugates.

The Jinchangyu deposit is the largest Au lode deposit in eastern Hebei Province of China and is located along the northern margin of the North China Craton. It was previously thought that this deposit was a greenstone belt-type as the orebodies are controlled by ductile shear structures in amphibolite units of the Archean Zunhua Group. However, new geological and petrographic observations presented here show that the mineralization was actually controlled by the brittle schistosity in the amphibolite and the ore-bearing quartz–albite veins are actually albite-rich granite porphyry dikes that coexist with graphic pegmatite dikes. Based on geological and geochemical features, we propose that the Jinchangyu Au deposit is actually a magmatic–hydrothermal type formed by melt–fluid derived from a highly fractionated magma. The ore-bearing albite-rich granite porphyry and pegmatite dikes are metaluminous to weakly peraluminous, and belong to the low-K tholeiitic to shoshonitic and subalkaline series. All the samples have high SiO2, K2O + Na2O contents and differentiation index values, low CaO, MgO, P2O5, and TiO2 contents, are enriched in Th, U, Ta, Nb, Sr, Zr, and Hf, depleted in Ba, K, P, Ti, and δEu, and exhibit the tetrad rare earth element effect. The mineralogy and geochemistry indicate the dikes are highly fractionated I-type granites, and that the Jinchangyu Au deposit was generated during magmatic differentiation. δ34S values of pyrite vary from –6.3‰ to 4.2‰, and H–O isotopic compositions of quartz from quartz–pyrite veins indicate the mineralizing fluid had a predominantly magmatic source. Lead isotope ratios (206Pb/204Pb = 15.65–16.18, 207Pb/204Pb = 15.16–15.29) of pyrite in the quartz–pyrite veins indicate the ore-forming materials were derived from a mixed source containing mantle and crustal materials. Geochemical features indicate that the dikes formed in a post-collsional extensional tectonic setting during the Late Triassic, after closure of the Paleo-Asian Ocean. Combined with data from previous studies, we propose that the parental magma and ore-forming materials of the Jinchangyu Au deposit were derived from a mixed source containing mantle and crustal material, underwent extensive differentiation, and then sequentially formed the ore-bearing albite-rich granite porphyry dike dikes, graphic pegmatite dikes, and quartz–albite, quartz–pyrite, and quartz–carbonate veins.

The development of efficient and earth abundant catalyst for the oxygen evolution reaction (OER) is a key challenge for the renewable energy research community. Here, we report a facile and ultrafast route to immobilize nickel-iron layered double hydroxide (NiFe-LDH) nanoparticles on nickel foam (NF) via soaking the direct electroless deposited prussian blue analogue (PBA) on NF in 1 M KOH. This NiFe-LDH/NF electrode can be prepared in a few seconds without further treatments. It has three-dimensional interpenetrating network originated from its PBA precursor which facilitate the diffusion and ad/desorption of the reactants and producing for OER. And further characterization of the Faradaic efficiency and forced convection tests show direct evidence to demonstrate the formation of free intermediate(s) in the OER process. This electrode (typically NiFe-LDH-20s/NF) exhibits outstanding electrocatalytic activity with low overpotential of ∼0.240 V at 10 mA cm−2, low Tafel slope of 38 mV dec−1, and great stability. This feasible strategy affords a new strategy for the large scale manufacture of low-cost, effective and robust OER electrodes.

Systematic spatial variations of anisotropic characteristics are revealed beneath the eastern U.S. using seismic data recorded between 1988-2016 by 785 stations. The resulting fast polarization orientations of the 5613 measurements are generally subparallel to the absolute plate motion (APM), and are inconsistent with the strike of major tectonic features. This inconsistency, together with the results of depth estimation using the spatial coherency of the splitting parameters, suggests a mostly asthenospheric origin of the observed azimuthal anisotropy. The observations can be explained by a combined effect of APM-induced mantle fabric and a flow system deflected horizontally around the edges of the keel of the North American continent. Beneath the southern and northeastern portions of the study area, the E-W keel-deflected flow enhances APM-induced fabric and produces mostly E-W fast orientations with large splitting times, while beneath the southeastern U.S., anisotropy from the N-S oriented flow is weakened by the APM.

Nonalcoholic fatty liver disease (NAFLD) is a growing global public health concern and becoming the leading cause of liver disease worldwide. The estimated global prevalence of NAFLD is ∼25% depending on the country and the assessment method used to establish the diagnosis. Meta-analyses suggest that the highest prevalence is in the Middle East (31.8%) and South America (30.4%), and the lowest in Africa (13.5%). In the United States, between 75 and 100 million individuals were estimated to have NAFLD. This important disease is associated with increased incidence of liver-related deaths, hepatocarcinoma, and overall mortality. Fibrosis stage, among other histological characteristics, is the most critical factor in predicting all-cause and disease-specific mortality in NAFLD. The ability to detect fibrosis early in NAFLD patients is critical in controlling mortality associated with this highly prevalent disease. We present here an expert review on recent advances in novel blood biomarkers, for example, the Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP), type IV collagen 7S, chitinase 3 like 1 (CHI3L1; YKL-40), and insulin-like growth factor-1 (IGF-1). Algorithms using multiple biomarkers such as alpha-2-macroglobulin, mir34a, YKL-40, and hemoglobin A1c (HbA1c; NIS4), enhanced liver fibrosis (ELF), Hepascore, FibroMeter, FibroTest, FIBROSpect, FIB-C3, and ADPAPT are highlighted. Novel technologies such as tandem mass spectrometry to directly measure protein turnover rate of the key proteins involved in hepatic fibrosis, as an indicator of fibrogenesis, are also discussed. In conclusion, NAFLD is a growing global health problem that warrants long-term funding, research, and training of scholars across the fields of public health diagnostics, systems sciences, nutrition, hepatology, and clinical oncology.

Three-dimensional (3D) culture of multicellular spheroids, offering a desirable biomimetic microenvironment, is appropriate for recapitulating tissue cellular adhesive complexity and revealing a more realistic drug response. However, current 3D culture methods are suffering from low-throughput, poor controllability, intensive-labor, and variation in spheroid size, thus not ready for many high-throughput screening applications including drug discovery and toxicity testing. Herein, we developed a high-throughput multicellular spheroid fabrication method using acoustofluidics. By acoustically-assembling cancer cells with low-cost and disposable devices, our method can produce more than 12 000 multicellular aggregates within several minutes and allow us to transfer these aggregates into ultra-low attachment dishes for long-term culture. This method can generate more than 6000 tumor spheroids per operation, and reduce tumor spheroid formation time to one day. Our platform has advantages in forming spheroids with high throughput, short time, and long-term effectiveness, and is easy-to-operation. This acoustofluidic spheroid assembly method provides a simple and efficient way to produce large numbers of uniform-sized spheroids for biomedical applications in translational medicine, pharmaceutical industry and basic life science research.

The 2013 Mw6.8 Lushan, China earthquake occurred in the southwestern end of the Longmenshan fault zone. We jointly invert local strong motion data and geodetic measurements of coseismic surface deformation, including GPS and InSAR, to obtain a robust model of the rupture process of the 2013 Lushan earthquake. Our joint inversion best model involves the rupture of two opposing faults during the Lushan earthquake, a main fault and a secondary fault. It is only when the secondary fault is included that both the GPS and InSAR measurements are fit along with the near-field strong motion. Over 75% of the computed moment was released in slip on the main fault segment, a northwest dipping, listric thrust fault, with buried thrust and dextral strike-slip at hypocenter depths, and with only minor slip closer to the surface. The secondary fault mainly involved oblique thrust slip or pure dextral strike-slip at shallower depths, and accounts for just under 24% of the moment released in the Lushan earthquake. Coulomb stress changes of about 0.5 MPa on the secondary fault segment at the time coseismic slip initiated on that fault indicate that slip was likely triggered by the coseismic slip on the main blind thrust fault. Our coseismic slip model is consistent with a sub-horizontal and east–west to southeast–northwest trending most compressive stress. Our inferred coseismic slip model is also consistent with previous GPS derived models of strain accumulation on the Longmenshan fault system.

The Supplementary Information originally published with this Article was an older version, in which 'IFN-γ' was misspelled 'INF-γ' in Supplementary Fig. 9 and the β-Actin blot in Supplementary Fig. 13 was the wrong image. The Supplementary Information has now been replaced.