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Despite regulators’ allegations that digital technology giants misuse their market power to earn abnormal profits, there is a dearth of systematic work on (1) whether digital-tech firms in general, and tech giants in particular, earn excess profits or (2) whether their abnormal profitability, if any, is due to market power. We use the following two alternative measures of economic profitability in addition to accounting rate of return (ARR): internal rate of return (IRR), which equates current investments to their long-term payback, and return on invested capital (ROIC), whose numerator (profits) and denominator (invested capital) are adjusted for capitalized intangibles. Inferences based on IRRs differ from those based on ARRs and ROICs. IRRs show that the digital-tech sector is now the best-performing sector, and its gap between profitability and cost of capital has increased over time. We are unable to separate the contribution of market power and innovation to digital tech’s high IRRs. JEL Classifications: D43; L1; M21; M41.

Research on China’s volunteerism highlights the state as a major force in mobilizing volunteer participation. Nevertheless, limited quantitative research exists documenting the extent to which Chinese volunteers are connected to the state system. Using a nationally representative dataset, the 2012 Chinese General Social Survey, this study examines how an individual’s employment affiliation with state-controlled institutions influences their probability to volunteer. The results show that the Chinese government not only directly mobilizes employees of the state system to volunteer but also has significant influence over the general population’s volunteering. This influence is mainly through the existence of Chinese Communist Party chapters in every corner of society, as well as the state’s direct and indirect control over social organizations that organize volunteer activities. We thus question the extent to which volunteerism in China is truly voluntary and call for more critical analysis of this issue.

BACKGROUND: Bladder cancer (BC) is the most common malignant tumor in the urinary system with a high incidence, imposing a burden on the healthcare system worldwide. The participation of long non-coding RNAs (lncRNAs) in BC has attracted increasing attention. OBJECTIVE: The aim in the current study was to explore the potential mechanism involving SH3BP5-AS1 in modulating BC cell proliferation, apoptosis and ferroptosis. METHODS: qPCR and WB analysis measured the expression of RNAs and proteins. Functional and mechanism experiments were performed to investigate RNA impacts on cell proliferation, apoptosis and ferroptosis, and explore the correlation between RNA and protein expression. RESULTS: SH3BP5-AS1 was down-regulated in BC cells, and SH3BP5-AS1 overexpression could inhibit BC cell proliferation but facilitate the cell apoptosis. SH3BP5-AS1 was also found to facilitate the ferroptosis of BC cells. Additionally, SH3BP5-AS1 was confirmed to recruit IGF2BP2 to regulate VDAC2 expression in the m6A-dependent manner. VDAC2 was detected to be down-regulated in BC cells and was verified to inhibit BC cell growth. Moreover, it was indicated from rescue assays that SH3BP5-AS1 could modulate VDAC2 expression to promote the ferroptosis of BC cells. CONCLUSION: SH3BP5-AS1 could affect BC cell proliferation, apoptosis and ferroptosis via IGF2BP2/VDAC2, providing a novel molecular perspective for understanding BC.

Recent studies have shown that autophagy plays an important role in gynecologic tumors, and ubiquitin modification of autophagy regulatory components is essential to regulate autophagic flux. In this study, we found that the ubiquitin-conjugating enzyme E2C (UBE2C) affects endometrial cancer cell apoptosis and proliferation by inhibiting autophagy. Electron microscopy observation of cell ultrastructure and experimental biochemical analysis showed that endometrial cancer cells with UBE2C expression knocked down display typical autophagic characteristics. Cells were cotreated with the autophagy pharmacologic inhibitors chloroquine and/or bafilomycin A1, and mRFP-GFP-LC3 assays were performed to monitor autophagic flux and determine whether UBE2C suppresses the autophagy program. Investigation of the corresponding mechanism by which UBE2C inhibits autophagy revealed that UBE2C induces K48-linked SIRT1 ubiquitination and promotes ubiquitination-dependent degradation of SIRT1, subsequently reducing H4K16 deacetylation levels and epigenetically inhibiting the expression of autophagy-related genes. The results of cell counting kit-8, Hoechst staining, and immunofluorescence assays further indicated that deletion of the autophagy-related gene BECN1 significantly attenuates UBE2C knockdown–induced cell apoptosis. Moreover, overexpression of UBE2C promoted tumor growth in the xenograft mice model. While, the introduction of rapamycin, an agonist of autophagy, successfully reversed tumor growth and apoptosis inhibition mediated by UBE2C overexpression in vitro and in vivo. Taken together, our results suggested that UBE2C-mediated ubiquitination and degradation of SIRT1 contribute to the malignant progression of endometrial cancer through epigenetic inhibition of autophagy. Implications: Our study highlights the tumorigenic role and regulatory mechanism of UBE2C in endometrial cancer; UBE2C inhibits endometrial cancer cell apoptosis through autophagy-related mechanisms and our findings provide new insights into the treatment of endometrial cancer.

The difference in equilibrium cations of the two compounds results in a big distinction in the dense hydrogen grid. This distinction further leads to the disparity in the proton conductivity of both compounds.

Supramolecular Cu(i) complexes are synthesized from 2,2′-bipyridine derivatives containing anion binding 1H-pyrazole and their applications in halogen sensing are studied.

Coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has escalated into a global tragedy afflicting human health, life, and social governance. Through the increasing depth of research and a better understanding of this disease, it has been ascertained that, in addition to the lungs, SARS-CoV-2 can also induce injuries to other organs including the liver. Liver injury is a common clinical manifestation of COVID-19, particularly in severe cases, and is often associated with a poorer prognosis and higher severity of COVID-19. This review focuses on the general existing information on liver injury caused by COVID-19, including risk factors and subpopulations of liver injury in COVID-19, the association between preexisting liver diseases and the severity of COVID-19, and the potential mechanisms by which SARS-CoV-2 affects the liver. This review may provide some useful information for the development of therapeutic and preventive strategies for COVID-19-associated liver injury.

Although CRISPR-Cas12a [clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 12a] combining pre-amplification technology has the advantage of high sensitivity in biosensing, its generality and specificity are insufficient, which greatly restrains its application range. Here, we discovered a new targeting substrate for LbaCas12a (Lachnospiraceae bacterium Cas12a), namely double-stranded DNA (dsDNA) with a sticky-end region (PAM−SE+ dsDNA). We discovered that CRISPR-Cas12a had special enzymatic properties for this substrate DNA, including the ability to recognize and cleave it without needing a protospacer adjacent motif (PAM) sequence and a high sensitivity to single-base mismatches in that substrate. Further mechanism studies revealed that guide RNA (gRNA) formed a triple-stranded flap structure with the substrate dsDNA. We also discovered the property of low-temperature activation of CRISPR-Cas12a and, by coupling with the unique DNA hybridization kinetics at low temperature, we constructed a complete workflow for low-abundance point mutation detection in real samples, which was fast, convenient and free of single-stranded DNA (ssDNA) transformation. The detection limits were 0.005–0.01% for synthesized strands and 0.01–0.05% for plasmid genomic DNA, and the mutation abundances provided by our system for 28 clinical samples were in accordance with next-generation sequencing results. We believe that our work not only reveals novel information about the target recognition mechanism of the CRISPR-Cas12a system, but also greatly broadens its application scenarios.

Refereed/Peer-reviewed Background: Upper arm lymphedema is a common complication one year after breast cancer surgery, which profoundly impacts patients' quality of life. Case summary: We reported a case of lymphedema induced by prolonged sun exposure 11 years after breast cancer surgery. Conclusion: Breast screening, patient education and follow-up after hospital discharge could help to prevent upper-arm lymphedema.

This article engages with the field of social work's role in humanitarian and criminal legal responses to sex work in the United States over the last century. Our historical review reveals that, through interdisciplinary collaboration in the criminalization and rehabilitation of sex workers, social workers have contributed to the transformation of “prostitution” from an issue of sex workers’ rights to a psychological, criminal legal, and medical phenomenon. This has exacerbated the harm and stigma experienced by sex workers. In exploring social work interventions on sex work from the Progressive Era through the rise of neoliberalism, this article places its modern iteration, prostitution diversion programming, within the context of social work's carceral history with sex workers. We choose these periods not for their chronicity, but rather for the salient themes in these historical interventions that characterize modern diversion programming: power and control, punitive service provision, patriarchal rescue, and carceral feminism. To align with social work's mandate for social justice and client self-determination, this article offers policy and practice implications grounded in the decriminalization of sex work and divestment from the police and courts. Alternative service approaches spearheaded by sex workers are explored and placed within the context of labor, racial, gender, and immigration justice.

SUMMARY Abnormal seismic activities near reservoirs usually show a strong spatiotemporal correlation with the water filling history. Reservoir-induced seismicity is thought to be related to crustal pore pressure and stress changes caused by water impounded behind the dams. Though the Coulomb-type stress analysis helps illuminate areas that would be under risk following reservoir impoundment, it lacks the ability to explain the temporal characteristics of reservoir-induced seismicity. We present a numerical investigation of the seismicity rate evolution of reservoir-induced earthquakes. Our modelling employs a fully coupled 2-D poroelastic model to calculate the pore pressure and stress changes caused by water impoundment and incorporates the rate- and state-dependent friction law to investigate the seismicity rate. We demonstrate that shallow earthquakes are mainly caused by pore pressure increase, while poroelastic stress transfer takes the dominant role at depth. Whether a fault would be brought close to failure depends on its geometrical properties and its relative location to the reservoir. The temporal evolution of reservoir-induced earthquakes is primarily controlled by tectonic environment instead of the diffusion of pore pressure.

Although resting-state fMRI studies support that human brain is topographically organized regarding localized and distributed processes, it is still unclear about the task-modulated cortical hierarchy in terms of distributed functional connectivity and localized timescales. To address, current study investigated the effect of cognitive load on cortical connectivity gradients and local timescales in the healthy brain using resting state fMRI as well as 1- and 2-back working memory task fMRI. The results demonstrated that (1) increased cognitive load was associated with lower principal gradient in transmodal cortices, higher principal gradient in primary cortices, decreased decay rate and reduced timescale variability; (2) global properties including gradient variability, timescale decay rate, timescale variability and network topology were all modulated by cognitive load, with timescale variability related to behavioral performance; and (3) at 2-back state, the timescale variability was indirectly and negatively linked with global network integration, which was mediated by gradient variability. In conclusion, current study provides novel evidence for load-modulated cortical connectivity gradients and local timescales during cognitive states, which could contribute to better understanding about cognitive load theory and brain disorders with cognitive dysfunction.

Electroacupuncture (EA) is a popular therapeutic therapy for premature ovarian insufficiency (POI). However, little has been known about the underlying processes of EA therapy. To investigate the benefit of EA and reveal the mechanism, thirty SD female rats were allocated into the control, model, sham, EA, and GnRHa groups at random. Vaginal smears were used to monitor the rats’ estrous cycle. Serum liver and renal function (ALT, AST, BUN, and Cr), sex hormone (FSH, E2, and AMH), oxidative stress markers (SOD, GSH, and MDA), and inflammatory cytokine (IL6, IL1β, and TNFα) levels were measured by enzyme-linked immunosorbent assay (ELISA). Their ovary morphology was observed by hematoxylin-eosin staining. Transmission electron microscope was used to remark the ultrastructure of the granulocytes. Protein and gene expressions of Keap1/Nrf2/HO-1 pathway were detected by western blot and RT-PCR. Compared with the model group, in the EA group, the levels of serum sex hormones recovered to normal levels. Moreover, it reduced oxidative stress in rats, as demonstrated by increased SOD and GSH levels and decreased MDA levels. Meanwhile, Keap1 mRNA and protein expression dropped considerably in the EA group, while the mRNA and protein expressions of Nrf2 and HO-1 increased. We found that preventive EA might rescue rats with CTX-induced ovarian dysfunction. The anti-inflammatory and antioxidative stress properties of EA, which elevated the Keap1/Nrf2/HO-1 signaling pathway, might be the underlying mechanism. Furthermore, as compared to GnRHa, electroacupuncture did not raise the burden of the liver (ALT and AST) or the kidney (BUN and Cr). Electroacupuncture has a meaningful impact and a sufficient level of safety, making it useful for therapeutic setting in POI.

Nomograms specifically used to predict the prognosis of ascending type nasopharyngeal carcinoma (NPC) have not been constructed.Data of ascending type (T3-4N0-1M0) NPC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were extracted.Altogether 862 patients with ascending type NPC were enrolled, including 603 in training cohort and 259 in validation cohort. Age, marital status, pathology, grade, tumor size, T classification, and chemotherapy were the independent prognostic factors for overall survival (OS). Age, marital status, pathology, grade, and chemotherapy were the independent prognostic factors for cancer-specific survival (CSS). In training cohort, the concordance index of the OS and CSS nomograms were 0.694 (95% confidence interval [CI], 0.677-0.711) and 0.678 (95%CI, 0.659-0.697), respectively, while those in validation cohort were 0.740 (95%CI, 0.715-0.765) and 0.708 (95%CI, 0.679-0.737), separately.The as-constructed nomograms for ascending type NPC could provide accurate prognostic predictions of OS and CSS.

Objective The most used drug for the treatment of rheumatoid arthritis (RA) remains methotrexate (MTX). Unfortunately, up to 50% of patients do not achieve a clinically adequate outcome. Here we study whether the gut microbiota patterns can aid in the prediction of MTX efficacy for RA. Method To dissect gut microbiome profiles of RA patients (n = 145), 16S rRNA gene sequencing was performed. Dirichlet multinomial mixture (DMM) clustering was used to identify enterotypes at genus level. The relationships between enterotypes and clinical measures (such as lymphocyte subsets and cytokines detected by flow cytometry) were explored. Then, enterotype stability was evaluated by the stratification of the RA patient cohort (n = 66) in Shanghai, China, using the same method. Finally, the enterotype-based gut microbial human index classifier was applied to another independent RA patient cohort (n = 27) to identify the factors associated with MTX clinical response. Results Our analysis revealed that the RA patients always displayed two different dysbiotic microbiota patterns: RA E1 comprised predominantly Prevotella and RA E2 comprised predominantly Bacteroides. Among all of the lymphocyte subsets and cytokines, only the number of CD8+ T cells showed a significant difference between RA E1 and RA E2. These results were validated in the RA patient cohort in Shanghai, China. Significant associations of RA E1 with clinical response to subsequent MTX treatment were confirmed by another independent RA patient cohort. Conclusion Together, the enterotype-based gut microbial human index (EGMI) classifier was useful to precisely and effectively identify enterotypes of individual RA patients, which could effectively evaluate MTX clinical responses.

Mollanol A is the first isolated member of the mollane-type grayanoids which possesses an unprecedented C-nor-D-homograyanane carbon skeleton and an 5,8-epoxide. Due to its transcriptional activation effects on the

This paper is concerned with the finite frequency H-/H∞ memory fault detection filtering problem for discretetime Takagi-Sugeno (T-S) fuzzy affine systems with normbounded uncertainties. The objective is to design a piecewise affine memory filter by using system historical information such that the resulting closed-loop filtering error system is asymptotically stable with the prescribed finite frequency H-/H∞ performance. Based on the generalized Kalman-YakubovicPopov (GKYP) lemma combined with the celebrated S-procedure, new sufficient conditions for the fuzzy affine filtering error system to have the finite frequency H-/H∞ performance are given at first. By further using piecewise fuzzy quadratic Lyapunov functions (PFQLFs) and Projection lemma, the filtering analysis results for the filtering error system to be asymptotically stable with the prescribed finite frequency H-/H∞ performance are obtained. Then the filtering synthesis is carried out with the aid of matrix inequality convexification techniques, and the synthesis results are described in terms of linear matrix inequalities (LMIs). It is further shown that better filtering performance can be achieved by using more system historical information. Finally, simulation is provided to verify the effectiveness of the proposed approach.

Place recognition is an essential spatial intelligence capability for robots to understand and navigate the world. However, recognizing places in natural environments remains a challenging task for robots because of resource limitations and changing environments. In contrast, humans and animals can robustly and efficiently recognize hundreds of thousands of places in different conditions. Here, we report a brain-inspired general place recognition system, dubbed NeuroGPR, that enables robots to recognize places by mimicking the neural mechanism of multimodal sensing, encoding, and computing through a continuum of space and time. Our system consists of a multimodal hybrid neural network (MHNN) that encodes and integrates multimodal cues from both conventional and neuromorphic sensors. Specifically, to encode different sensory cues, we built various neural networks of spatial view cells, place cells, head direction cells, and time cells. To integrate these cues, we designed a multiscale liquid state machine that can process and fuse multimodal information effectively and asynchronously using diverse neuronal dynamics and bioinspired inhibitory circuits. We deployed the MHNN on Tianjic, a hybrid neuromorphic chip, and integrated it into a quadruped robot. Our results show that NeuroGPR achieves better performance compared with conventional and existing biologically inspired approaches, exhibiting robustness to diverse environmental uncertainty, including perceptual aliasing, motion blur, light, or weather changes. Running NeuroGPR as an overall multi–neural network workload on Tianjic showcases its advantages with 10.5 times lower latency and 43.6% lower power consumption than the commonly used mobile robot processor Jetson Xavier NX.

Ferroptosis is a form of programmed cell death with important biological functions in the progression of various diseases, and targeting ferroptosis is a new tumor treatment strategy. Studies have shown that sodium butyrate plays a tumor-suppressing role in the progression of various tumors, however, the mechanism of NaBu in endometrial cancer is unclear. Cell viability, clone formation, proliferation, migration, invasion abilities and cell cycle distribution were assessed by CCK8 assay, Clone formation ability assay, EdU incorporation, Transwell chambers and flow cytometry. The level of ferroptosis was assayed by the levels of ROS and lipid peroxidation, the ratio of GSH/GSSG and the morphology of mitochondria. Molecular mechanisms were explored by metabolome, transcriptome, RNA-pulldown and mass spectrometry. The in-vivo mechanism was validated using subcutaneous xenograft model. In this study, NaBu was identified to inhibit the progression of endometrial cancer in vitro and in vivo. Mechanistically, RBM3 has a binding relationship with SLC7A11 mRNA. NaBu indirectly downregulates the expression of SLC7A11 by promoting the expression of RBM3, thereby promoting ferroptosis in endometrial cancer cells. In conclusion, Sodium butyrate can promote the expression of RBM3 and indirectly downregulate the expression of SLC7A11 to stimulate ferroptosis, which may be a promising cancer treatment strategy.

Figure S8

Table S1. Primers for qPCR

Figure S2