Miracle-dz/UniFAR-FTUs huggingface dataset:
Servitization for the Environment? The Impact of Data-Centric Product-Service Models

ABSTRACT Recent developments in data-centric technologies (e.g., big data, Internet of Things, cloud computing) have given rise to the data-centric models, such as servitization. Servitization here refers to firms selling a product as a service instead of selling product ownership, which has been viewed as a green business model that can benefit the environment. Despite the potential environmental superiority of servitization, previous studies and empirical observations have shown that the servitization model may generate lower profits than the conventional product sales model, which poses challenges for firms to choose their business models. However, the existing literature has not considered the role of data-centric technologies that are increasingly embedded in the servitization model, in which firms can co-create value with consumers by leveraging product usage data to improve service offerings. In this study, we build an analytical model to scrutinize the economic and environmental performance of the data-centric servitization model compared to the product model. We find that the data-centric servitization model is more profitable than the product model only when a firm’s service improvement capability is relatively high. Unfortunately, a high service improvement capability may exacerbate the negative environmental impact, resulting in the servitization model being less environmentally friendly than the product model. We discuss the circumstances under which using the servitization model can yield win-win outcomes in terms of profitability and environmental impact. The findings can help managers and policymakers reconcile the tension between firm profitability and environmental damage and make judicious decisions on business model choices and the application of emerging data-centric technologies.
How Appreciation and Attention Affect Contributions to Electronic Networks of Practice

ABSTRACT We conducted three studies to examine how two types of user-generated feedback, appreciation and attention, affect users’ decisions to make voluntary knowledge contributions to electronic networks of practice (ENPs). Appreciation is reflected in positive ratings, votes, and helpfulness evaluations. Attention is reflected in the number of views of contributed content. The first study used clickstream data from a college application ENP in China, where information seekers can read posted information asynchronously and request synchronous consultations with volunteers. The second study was a controlled online experiment in the United States where we assessed users’ willingness to answer questions in a college application ENP asynchronously. The third study examined knowledge contribution across a diverse set of topics using a well-established ENP that serves more than 100 countries. In all three studies, the results consistently show that greater appreciation increased continued knowledge contribution, but greater attention without sufficient appreciation negatively affected contributions. Our findings show the theoretically intertwined nature of attention and appreciation and offer insights for the design and management of ENP feedback systems to encourage user contributions.
Joint optimization algorithm of user association and power control based on spatial traffic distribution

5G networks must reduce network overhead while meeting user needs. Based on the flow model, this paper jointly optimizes the user association and power control in cellular networks, aiming at achieving a reasonable compromise between user delay and network energy consumption. Unlike previous snapshot models, flow models focus on the spatial distribution of traffic demand instead of the specific location of users. We consider a nonuniformity of spatial traffic distribution and load coupling among base stations (BSs). Firstly, an iterative algorithm is proposed to solve the optimal user association strategy under certain power of BSs. Then, a greedy power adjustment and user association algorithm (GPA‐UA) is proposed to further optimize the objective function. The simulation results show that the proposed algorithm can reduce both user delay and network energy consumption in most cases, and the performance of the proposed algorithm is approximate to the Optimal scheme while GPA‐UA has lower complexity.
On basic properties of convex functions and convex integrands

f_{n} arrow\inf f as narrow\infty with some conditions where the sequence \{f_{n}\} converges decreasingly to f, and each f_{n} and f belong to a certain class of convex functions. In addition, the \tau-convergence of convex functions was considered in [6], [7], and [13], and the equivalence between the \tau convergence of \{f_{n}\} and that of \{f_{n}^{*}\} was derived with some hypotheses. In this paper, we deal with only the pointwise convergence, and prove some results about the convergence of inf f_{n} and that of \{f_{n}^{*}\} with natural hypotheses. In Chapter 2, we deal with a type of convex integrands, and derive some formulas for them. In our preceding paper [4], we considered convex operators \overline{f} : R\supset D(\tilde{f})arrow S(\Omega) where R is the space of real numbers and S(\Omega) is the linear space of finite valued measurable functions on a finite measure space \Omega . We proved that \tilde{f} is represented by a convex integrand f(\cdot, \cdot) : R
Antigen presentation by clonally diverse CXCR5+ B cells to CD4 and CD8 T cells is associated with durable response to immune checkpoint inhibitors

Introduction Increased T cell infiltration and interferon gamma (IFNγ) pathway activation are seen in tumors of melanoma patients who respond to ICI (immune checkpoint inhibitor) or MAPK pathway inhibitor (MAPKi) therapies. Yet, the rate of durable tumor control after ICI is almost twice that of MAPKi, suggesting that additional mechanisms may be present in patients responding to ICI therapy that are beneficial for anti-tumor immunity. Methods We used transcriptional analysis and clinical outcomes from patients treated with ICI or MAPKi therapies to delineate immune mechanisms driving tumor response. Results We discovered response to ICI is associated with CXCL13-driven recruitment of CXCR5+ B cells with significantly higher clonal diversity than MAPKi. Our in vitro data indicate that CXCL13 production was increased in human peripheral blood mononuclear cells by anti-PD1, but not MAPKi, treatment. Higher B cell infiltration and B cell receptor (BCR) diversity allows presentation of diverse tumor antigens by B cells, resulting in activation of follicular helper CD4 T cells (Tfh) and tumor reactive CD8 T cells after ICI therapy. Higher BCR diversity and IFNγ pathway score post-ICI are associated with significantly longer patient survival compared to those with either one or none. Conclusions Response to ICI, but not to MAPKi, depends on the recruitment of CXCR5+ B cells into the tumor microenvironment and their productive tumor antigen presentation to follicular helper and cytotoxic, tumor reactive T cells. Our study highlights the potential of CXCL13 and B cell based strategies to enhance the rate of durable response in melanoma patients treated with ICI.
Multiple GC-biased repetitive ITS copies in the Hirsutella sinensis genome are 1 not generated by RIP mutagenesis involving transition point mutations 2 3

5 a State Key Laboratory of Plateau Ecology and Agriculture, Qinghai Academy of Animal and 6 Veterinary Sciences, Qinghai University, Xining, Qinghai 810016, China 7 b State Key Laboratory of Breeding Base of Dao-di Herbs, National Resource Center for Chinese 8 Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China 9 c Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, 10 Tsinghua University, Shenzhen 518055, China 11 12 * Corresponding author: 13
Evaluation of the Efficacy of the Hypocretin/orexin Receptor Agonists TAK-925 and ARN-776 in Narcoleptic Orexin/tTA; TetO-DTA Mice

The sleep disorder Narcolepsy, a hypocretin deficiency disorder thought to be due to degeneration of hypothalamic hypocretin/orexin neurons, is currently treated symptomatically. We evaluated the efficacy of two small molecule hypocretin/orexin receptor-2 (HCRTR2) agonists in narcoleptic male orexin/tTA; TetO-DTA mice. TAK- 925 (1-10 mg/kg, s.c.) and ARN-776 (1-10 mg/kg, i.p.) were injected 15 min before dark onset in a repeated measures design. EEG, EMG, subcutaneous temperature (Tsc) and activity were recorded by telemetry; recordings for the first 6-h of the dark period were scored for sleep/wake and cataplexy. At all doses tested, TAK-925 and ARN-776 caused continuous wakefulness and eliminated sleep for the first hour. Both TAK-925 and ARN-776 caused dose-related delays in NREM sleep onset. All doses of TAK-925 and all but the lowest dose of ARN-776 eliminated cataplexy during the first hour after treatment; the anti-cataplectic effect of TAK-925 persisted into the 2nd hour for the highest dose. TAK-925 and ARN-776 also reduced the cumulative amount of cataplexy during the 6-h post-dosing period. The acute increase in wakefulness produced by both HCRTR2 agonists was characterized by increased spectral power in the gamma EEG band. Although neither compound provoked a NREM sleep rebound, both compounds affected NREM EEG during the 2nd hour post-dosing. TAK-925 and ARN-776 also increased gross motor activity, running wheel activity and Tsc, suggesting that the wake-promoting and sleep-suppressing activities of these compounds could be a consequence of hyperactivity. Nonetheless, the anti-cataplectic activity of TAK-925 and ARN-776 is encouraging for the development of HcrtR2 agonists.
ROTACs leverage signaling-incompetent R-spondin for targeted protein degradation

Proteolysis-targeting chimeras (PROTACs) are an emerging technology for therapeutic intervention but options to target cell surface proteins and receptors remain limited. Here we introduce ROTACs, bispecific WNT- and BMP signaling-disabled R-spondin (RSPO) chimeras, which leverage the specificity of these stem cell growth factors for ZNRF3/RNF43 E3 transmembrane ligases, to target degradation of transmembrane proteins. As proof of concept, we targeted the immune checkpoint protein programmed death ligand 1 (PD-L1), a prominent cancer therapeutic target, with a bispecific RSPO2 chimera, R2PD1. The R2PD1 chimeric protein bound PD-L1 and at picomolar concentration induced its lysosomal degradation. In three melanoma cell lines, R2PD1 induced between 50-90% PD-L1 protein degradation. PD-L1 degradation was strictly dependent on ZNRF3/RNF43. We conclude that signaling-disabled ROTACs represent a novel strategy to target cell surface proteins for degradation.
Random genetic drift sets an upper limit on mRNA splicing accuracy in metazoans

Most eukaryotic genes undergo alternative splicing (AS), but the overall functional significance of this process remains a controversial issue. It has been noticed that the complexity of organisms (assayed by the number of distinct cell types) correlates positively with their genome-wide AS rate. This has been interpreted as evidence that AS plays an important role in adaptive evolution by increasing the functional repertoires of genomes. However, this observation also fits with a totally opposite interpretation: given that ‘complex’ organisms tend to have small effective population sizes (Ne), they are expected to be more affected by genetic drift, and hence more prone to accumulate deleterious mutations that decrease splicing accuracy. Thus, according to this “drift barrier” theory, the elevated AS rate in complex organisms might simply result from a higher splicing error rate. To test this hypothesis, we analyzed 3,496 transcriptome sequencing samples to quantify AS in 53 metazoan species spanning a wide range of Ne values. Our results show a negative correlation between Ne proxies and the genome-wide AS rates among species, consistent with the drift barrier hypothesis. This pattern is dominated by low abundance isoforms, which represent the vast majority of the splice variant repertoire. We show that these low abundance isoforms are depleted in functional AS events, and most likely correspond to errors. Conversely, the AS rate of abundant isoforms, which are relatively enriched in functional AS events, tends to be lower in more complex species. All these observations are consistent with the hypothesis that variation in AS rates across metazoans reflects the limits set by drift on the capacity of selection to prevent gene expression errors.
Lipid remodeling by hypoxia aggravates migratory potential in pancreatic cancer while maintaining membrane homeostasis

Membranes are crucial cell components underlying optimal cellular functioning under diverse conditions including cancer. The membrane physiology requires acute maintenance of biophysical properties and a regulation of cellular lipidome. Homeostatic adaptation of membranes to temperature, pressure and anti-cancer drugs is a well-recognized. However, how the same is regulated under the influence of oxygen deprivation in pancreatic cancers-highly hypoxic cancer- is not known. Here, we report robust lipidomic remodelling in response to HIF-1α induction in pancreatic cancer cells and significant accumulation of lipid droplets. The lipidome rewiring span changes across various lipid classes, levels of unsaturation and acyl chain lengths. Interestingly, despite extensive lipidome alteration, cellular membrane homeostatic response ensures no major modulation of membrane biophysical properties underlying enhanced migratory potential. The correlation of lipidome changes, with pathway analysis and proteomics provide the basis for mutually exclusive regulation of lipidome and membrane properties. These findings help to understand the hypoxic regulation of pancreatic membrane homeostasis.
Circadian reprogramming of adipose progenitor cells regulates intermittent fasting-mediated adipose tissue remodeling and metabolic improvement

White adipose tissue (WAT) fibrosis is a hallmark of dysfunctional WAT that is directly linked to metabolic abnormalities. Recent studies have highlighted the role of dysfunctional adipose progenitor cells (APCs) in WAT fibrosis and impaired adaptive tissue plasticity, leading to systemic insulin resistance. However, therapeutic options for WAT fibrosis are limited. Intermittent fasting (IF) is an effective dietary regimen for weight control and metabolic improvement through various mechanisms, including healthy remodeling of WAT. However, whether IF is effective in improving age-associated WAT fibrosis and metabolic homeostasis is unknown. Here, we show that IF confers therapeutic benefits in aged and obese mice through reduction of WAT fibrosis. Single-cell analyses revealed that IF significantly reduces pro-fibrotic signatures within APCs along with upregulation of the circadian pathways, suggesting that the circadian clock of APCs mediates IF-induced WAT remodeling. Importantly, mice lacking core circadian gene exhibited increased fibrotic signatures in WAT and diminished beneficial response to IF, further supporting the importance of circadian rhythm in IF-mediated metabolic benefits. Lastly, insulin resistance in humans also presented with dysregulated circadian rhythm signatures in APC populations. Collectively, our findings highlight the novel role of the APC circadian rhythm in plasticity of WAT and metabolic response to IF.
The impact of sex and physical activity on the local immune response to muscle pain

Induction of muscle pain triggers a local immune response to produce pain and this mechanism may be sex and activity level dependent. The purpose of this study was to measure the immune system response in the muscle following induction of pain in sedentary and physically active mice. Muscle pain was produced via an activity-induced pain model using acidic saline combined with fatiguing muscle contractions. Prior to induction of muscle pain, mice (C57/BL6) were sedentary or physically active (24hr access to running wheel) for 8 weeks. The ipsilateral gastrocnemius was harvested 24hr after induction of muscle pain for RNA sequencing or flow cytometry. RNA sequencing revealed activation of several immune pathways in both sexes after induction of muscle pain, and these pathways were attenuated in physically active females. Uniquely in females, the antigen processing and presentation pathway with MHC II signaling was activated after induction of muscle pain; activation of this pathway was blocked by physical activity. Blockade of MHC II attenuated development of muscle hyperalgesia exclusively in females. Induction of muscle pain increased the number of macrophages and T-cells in the muscle in both sexes, measured by flow cytometry. In both sexes, the phenotype of macrophages shifted toward a pro-inflammatory state after induction of muscle pain in sedentary mice (M1+M1/2) but toward an anti-inflammatory state in physically active mice (M2+M0). Thus, induction of muscle pain activates the immune system with sex-specific differences in the transcriptome while physical activity attenuates immune response in females and alters macrophage phenotype in both sexes.
Genome-wide association reveals novel insights into the molecular mechanisms regulating stem volume in Pinus taeda

Pinus taeda (loblolly pine [LP]) is a long-lived tree species and one of the most economically significant forest species. Among growth traits, volume is the most widely considered trait in tree improvement programs. However, deciphering the genetic variants responsible for growth trait variations in conifers, such as LP, is particularly challenging due to the vast size and intricate complexity of Pinus genomes. We present a comprehensive genetic analysis of LP, focusing on markers associated with stem volume variation, to elucidate the molecular mechanisms governing high-performance phenotypes. We used a population of 1,692 individuals phenotyped for stem volume and genotyped these individuals using sequence capture probes. To conduct genome-wide associations, we utilized both genome-wide association study (GWAS) analysis and machine learning (ML) approaches. The markers identified in association with volume were found to be linked with the genes assembled from three distinct transcriptomes. These genes were subsequently used to construct gene coexpression networks, and through topological evaluations, we identified key genes with potential regulatory roles within stem volume configurations. Using a set of 31,589 SNPs, we defined 7 GWAS-associated SNPs and 128 ML-associated markers, all of which were correlated with multiple genes involved in diverse biological functions. Gene coexpression analysis revealed a group of 270 genes potentially associated with the regulation of genetic material. Key genes directly implicated in the regulation of growth and response to stress were identified, and inferences about their impact on pine development were subsequently elucidated. Our study not only offers insights into SNPs associated with stem volume but also elucidates a subset of genes characterized by unique regulatory features. These findings significantly advance our understanding of the genetic factors influencing growth traits, reveal candidate genes for future functional studies, and contribute to a broader comprehension of the genetic architecture underlying volume traits in LP.
Composition efficacy of Unsaturated Arachidonic acid, Diterpenoids, Malvin (C29H35ClO17), and Bergenin to neutralise venom from different venomous snake species

Snakebite envenomation is a serious problem in tropical and subtropical countries. Antivenom is the only treatment used to treat snake envenomation, however it is unable to neutralise local haemorrhage. Therefore, this study’s aim is to evaluate the efficacy of P. dulce leaf extract to neutralise local haemorrhage induced by three clinically important snake species, B. jararaca, C. atrox and E. carinatus. Moreover, to determine the active components which are responsible for this activity. The plant leaves were extracted using different solvents, however, only E/e extract showed the best neutralizing capacity. The increasing doses, DF-1:2; 1:4, of E/e extract allowed better neutralizing ability s.c. In contrast, the oral/ i.p. acute toxicity test revealed that the optimal doses for the administration of E/e were 1 and 8 mg/kg. In addition to that, E/e was tested for its anti-lathality of LD50 using B. jararaca venom (1.1mg/kg) i.p., where the higher doses of 16 and 24 mg/kg killed 75% of BALB/C mice. Consequently, the different components of E/e extract were isolated with HPLC. The different components were grouped and tested to uncover the active ones. The results revealed that only three fractions were active, Frc11, Frc13, and Frc14. The active fractions showed a disparity in neutralizing the individual venoms, however, the best neutralising capacity was scored for Frc11. When the same fractions were pooled together, they showed a complete neutralizing ability against individual venoms as well as the pooled venoms. That was confirmed with the anti-gelatinase activity test, where pooled fraction inhibited the SVMP enzyme which is responsible for gelatinase activity. The phytochemical characterisation showed that the active fractions consist mainly of secondary metabolites such as tannins and polyphenols. MALDI-TOF MS confirmed the presence of secondary metabolites in the active fractions. The same fractions were tested for their anti-lethal activity using the pooled venoms (LD100), the results were statistically not significant, as all mice died including the positive controls. Nevertheless, the active fractions showed a noticeable increasing in survival time period especially Frc13 with an average survival time of 37 minutes. The positive control, IAV, scored the longest survival period with a gap of 11 minutes from Frc13.
Dalpiciclib partially abrogates ER signaling activation induced by pyrotinib in HER2+HR+ breast cancer

Background Recent evidences from clinical trials (NCT04486911) revealed that the combination of pyrotinib, letrozole and dalpiciclib exerted optimistic therapeutic effect to treat HER2+HR+ breast cancer, however, the underlying molecular mechanism remained further investigation. Methods Through the drug sensitivity test, the drug combination efficacy of pyrotinib, tamoxifen and dalpiciclib to BT474 cells were tested. The underlying molecular mechanisms were investigated using immunofluorescence, western blot analysis, immunohistochemical staining and cell cycle analysis. Potential risk factor which may indicate the responsiveness to drug treatment in HER2+/HR+ breast cancer was selected out using RNA-sequence and tested using immunohistochemical staining and in vivo drug susceptibility test. Results We found that pyrotinib combined with dalpiciclib exerted better cytotoxic efficacy than pyrotinib combined with tamoxifen in BT474 cells. Degradation of HER2 could enhance ER nuclear transportation, activating ER signaling pathway in BT474 cells whereas dalpiciclib could partially abrogate this process. This may be the underlying mechanism by which combination of pyrotinib, tamoxifen and dalpiciclib exerted best cytotoxic effect. Furthermore, CALML5 was revealed to be a risk factor in the treatment of HER2+/HR+ breast cancer and the usage of dalpiciclib might overcome this. Conclusion Our study provided evidence that the usage of dalpiciclib in the treatment of HER2+/HR+ breast cancer could partially abrogate the estrogen signaling pathway activation caused by anti-HER2 therapy and revealed that CALML5 could serve as a risk factor in the treatment of HER2+/HR+ breast cancer. Funding This study was supported by the National Natural Science Foundation of China (#U20A20381, #81872159)