Search

Abstract The contribution of knowledge capital to firm value has increased significantly, from 25% in the 1970s to 45% in the 2010s (Belo et al. in Decomposing firm value J Financ Econ 143:619–639, 2022). However, what influences firms’ ability to maximize the effect of knowledge capital on firm value? Drawing on insights from upper echelons, agency, and behavioral agency theories, we show that CEO characteristics are crucial in enabling firms to take advantage of knowledge stock. We empirically demonstrate that short-term CEO compensation structures are detrimental to a firm’s ability to take advantage of its knowledge stock. We further show that CEO power enhances knowledge stock and R&D intensity. Our study provides direct empirical evidence of the importance of CEO compensation structure and corporate governance in understanding firm value in a knowledge economy.

Abstract Background Previous research on the lower gastrointestinal tract has proved that microbial dysbiosis can lead to intestinal barrier dysfunction and enhanced visceral sensitivity, thus triggering bowel symptoms. Whether esophageal microbial dysbiosis also contributes to the development of gastroesophageal reflux (GER) symptoms, which are known to be associated with impaired esophageal barrier integrity, remains to be explored. Methods Patients with GER symptoms (gastroesophageal reflux disease [GERD] and functional esophageal disorders [FED]), duodenal ulcer patients and healthy controls were prospectively included for esophageal microbial analysis. The expression of toll-like receptors (TLRs) and tight junction proteins and intercellular spaces were assessed through transcriptome analysis and immunohistochemistry. The human esophageal epithelial cell (HEEC) line was used to explore how esophageal microbial dysbiosis induced GER symptoms. Results Patients with GER symptoms, whether GERD or FED, had a very similar pattern of microbial composition, which showed a significantly increased proportion of Gram-negative bacteria than controls. Patients with GER symptoms (GERD and FED) also exhibited significantly higher TLR2 expression, reduced claudin-1 expression and dilated intercellular spaces (DIS). In vitro, exposure of HEECs to lipopolysaccharide resulted in marked up-regulation of TLR2 and interleukin (IL)-6, down-regulation of claudin-1 and DIS. These effects were mitigated by blocking TLR2 or IL-6. Conclusion This study demonstrated that regardless of objective evidence of reflux, patients with GER symptoms presented esophageal microbial dysbiosis characterized by an elevated proportion of Gram-negative bacteria. Enriched Gram-negative bacteria could induce esophageal barrier dysfunction via LPS-TLR2-IL-6-claudin-1-DIS pathway.

Abstract LC3-associated phagocytosis (LAP) is critical in host defense against invading pathogens, but the molecular mechanism for LAP activation is still unclear. Here, we find programmed cell death 6 (PDCD6) as a negative regulator of LAP. PDCD6 deficiency in mice and macrophages induces enhanced bactericidal activity and LAP formation. In parallel, lactate dehydrogenase A (LDHA) activity and lactate production is induced in macrophages challenged with bacteria, Zymosan or Pam3CSK4, while genetic ablation or pharmacological inhibition of LDHA reduces lactate levels and impairs bactericidal activity in vivo and in vitro. Mechanistically, PDCD6 interacts with LDHA to downregulate lactate metabolism, leading to reduced RUBCN lactylation at lysine33 (K33). By contrast, PDCD6-deficiency increases RUBCN lactylation, thereby promotes RUBCN interaction with VPS34, LAP formation, and protective responses. Our results thus suggest a PDCD6-LDHA-lactate-RUBCN axis of innate immunity regulation that may both contribute to protection from infectious diseases and serve as targets for therapeutic development.

Abstract Background The Plant-specific AP2/ERF gene family encodes proteins involved in various biological and physiological processes. Although the genome of Coptis chinensis Franch, a plant producing benzylisoquinoline alkaloids (BIAs), has been sequenced at the chromosome level, studies on the AP2/ERF gene family in C. chinensis are lacking. Thus, a genome-wide identification of AP2/ERF gene family in C. chinensis was conducted to explore its role in BIAs biosynthesis. Results A total of 96 CcAP2/ERF genes were identified and categorized into five subfamilies, including 43 ERFs, 32 DREBs, 17 AP2s, 3 RAVs, and 1 Soloist, based on their structural domains. These CcAP2/ERF genes were unevenly distributed across nine chromosomes. Analysis of gene duplication events identified 17 CcAP2/ERF gene pairs in the genome, with 7 involved in tandem duplication events and 10 involved in segmental duplicate events, indicating that both types of duplications contributed to the expansion of the AP2/ERF gene family. The Ka/Ks ratio analysis suggested that the CcAP2/ERF gene family underwent strong purifying selection. Two phytohormones, methyl jasmonate and abscisic acid, were identified as potential key inducers of BIAs biosynthesis due to the cis-acting element prediction. Analysis of the spatial transcriptomic data revealed that 28 differentially expressed AP2/ERF genes had the highest or relatively higher expression levels in the rhizome, 17 of which positively correlated with the tissue-specific accumulation of BIAs. Further real-time PCR verification and protein-protein interaction analysis indicated that DREB1B might be one of the central regulators in a highly complex BIAs biosynthesis network. Conclusion These findings provide significant insight into the function of AP2/ERF genes in C. chinensis, particularly in the regulatory network of BIAs biosynthesis in C. chinensis. This study also identifies candidate genes for metabolic engineering to increase BIAs content in C. chinensis.

Toxoplasma gondii is a globally significant zoonotic pathogen responsible for congenital disorders and opportunistic infections, primarily transmitted through foodborne pathways. Deer are considered high-risk hosts for T. gondii infection; however, data on its prevalence in their muscle tissues remain limited. This study assessed the prevalence of T. gondii in 168 fresh venison samples collected in Montreal in 2024. The sensitivity of conventional PCR and nested PCR methods for detecting the RE-529 fragment was compared. Nested PCR exhibited a detection limit of 2 fg/μL, which is 100 times more sensitive than that of conventional PCR. Using nested PCR, T. gondii DNA was detected in 73 out of 168 samples, indicating a high positivity rate of 43.45 %. These findings reveal the widespread prevalence of T. gondii in venison sold in Montreal and emphasize the importance of freezing or thoroughly cooking venison to mitigate the risk of foodborne toxoplasmosis. This study provides baseline data for health risk assessments and contributes to the development of food safety policies in Canada.

Abstract The large variation in net ecosystem productivity (NEP) with forest age was dominated by the dynamics of net primary productivity (NPP)–which in turn was determined by the different response slopes of gross primary productivity (GPP) and autotrophic respiration (Ra) with forest age. However, only few models can comprehensively represent the impacts of forest age and global changes including land‐use change, climate change, nitrogen deposition, and atmospheric CO2 from the perspective of ecological processes. Based on a process‐based model (CEVSA‐ES) that included these global changes, we developed an ecosystem carbon sink assessment model considering forest age dynamics (CEVSA‐AgeD) using satellite‐based relationships between GPP (or Ra) and forest age to constrain photosynthesis and autotrophic respiration processes. Subsequently, we used a model data‐fusion framework combined with carbon flux observations to calibrate the model. The calibrated CEVSA‐AgeD model performed well in simulating seasonal (R2 values for GPP, ecosystem respiration, and NEP were 0.86, 0.79, and 0.66, respectively) and annual carbon flux changes (R2 of GPP, ecosystem respiration, and NEP were 0.83, 0.77, and 0.67, respectively). The magnitude of average NEP in China estimated using this model was 0.35 ± 0.005 TgC/yr from 2001 to 2021, which was close to previous estimates, and the dynamics of forests age increased NEP by 87–92 TgC/yr. These results indicate that the CEVSA‐AgeD model performed well in simulating carbon fluxes at the site and regional scales and that it was necessary to incorporate the effect of forest age dynamics on carbon cycling processes into process‐based models.

Objective:. The Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure (PADN-5) study proved that pulmonary artery denervation (PADN) is associated with significant improvements in hemodynamic and clinical outcomes in patients with combined pre- and post-capillary pulmonary hypertension (CpcPH). This study aimed to assess the 3-year clinical results of PADN in patients who had heart failure with preserved ejection fraction (HFpEF) developing into CpcPH (HFpEF-CpcPH). Methods:. In this post hoc analysis of the PADN-5 trial, 38 patients with HFpEF were included in screening out of 98 patients with CpcPH who were randomly assigned to treatment with sildenafil and sham PADN (sham PADN (plus sildenafil) group, abbreviated as sham group) or PADN (PADN group). HFpEF in the PADN-5 trial was defined as a left ventricular ejection fraction ≥50%, and CpcPH was defined as a mean pulmonary arterial pressure ≥25 mmHg, a pulmonary arterial wedge pressure >15 mmHg, and a pulmonary vascular resistance >3.0 WU. The changes in the 6-minute walk distance (6-MWD) and the plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) at 6-month and 3-year follow-up, as well as the clinical endpoint of the occurrence of clinical worsening, defined as cardiopulmonary-related death, rehospitalization, or heart or lung transplantation at 3-year follow-up were examined. Results:. Thirty-eight patients with HFpEF-CpcPH were assigned to the PADN group (n = 19) or the sham group (n = 19). At the 6-month follow-up, 6-MWD (433 (275, 580)m vs. 342 (161, 552)m), and reductions in NT-proBNP (−47% (−99%, 331%) vs. −12% (−82%, 54%)) were significantly improved in the PADN group (all P < 0.05). Over the 3-year follow-up period, PADN treatment resulted in marked increases in 6-MWD (450 (186, 510)m vs. 348 (135, 435)m) and reductions in NT-proBNP (−55% (−99%, 38%) vs. −10% (−80%, 95%)) (all P < 0.05). Clinical worsening was experienced by 12 patients (63%) in the sham group, but by only 5 patients (26%) in the PADN group (hazard ratio = 0.149, 95% confidence interval: 0.038–0.584, P = 0.006). The 6-MWD and PADN treatments were independent predictors of clinical deterioration in patients with HFpEF-CpcPH. Conclusions:. PADN therapy is associated with improvements in exercise capacity and clinical outcomes. PADN therapy may have a potential role in patients with HFpEF-CpcPH for whom current treatment options are limited.

In order to solve the problems of low efficiency and cumbersome process of Pichia pastoris genetic manipulation, secretory genetic manipulation tools were constructed and optimized to improve their industrial production and application value. Firstly, the α-amylase was employed as the reporter protein, and the non-integrated expression plasmid was constructed by fusing the self-replicating sequence. Secondly, endogenous signal peptides that best match the target protein were quickly screened and evaluated using universal primers and POE-PCR. Finally, a nutrition-dependent screening marker was constructed with phosphite as the sole phosphorus source. The results indicate that non-integrated plasmids express α-amylase with 2-fold and 1.6-fold higher enzyme activity compared to integrated plasmids, respectively; The use of FLO10, EXG1, and MSB2 signal peptides results in 2.5-fold, 1.94-fold, and 1.75-fold higher α-amylase activity than the conventional signal peptide α-MF, respectively; Arecombinant strain for heterologous expression of α-amylase is successfully screened using the phosphite dehydrogenase gene (ptxD). The process of gene operation is simplified, the genetic operation tools are improved, and green, safe, and low-cost nutrition-dependent screening markers are provided, which lays a foundation for the application and promotion of the Pichia pastoris secretory expression system.

Study region: Yellow River Delta (YRD), China's youngest wetland ecosystem Study focus: Drastic land use and cover change (LUCC), along with environmental shifts, have significantly affected evapotranspiration (ET) in YRD. However, few studies have examined the spatiotemporal patterns and drivers of ET due to satellite-based data constraints. We used the PT-JPL model and Dalton formula based on high-resolution satellite data to simulate ET from 2000 to 2023 and quantified the relative contributions of LUCC and environmental factors. New hydrological insight for the region: ET in YRD has significantly increased over the past decades, with an annual rise of 2.13 × 10⁻² gigatons of water per year (P

F-box proteins play crucial roles in various developmental stages in plants, such as shoot branching. As an important ornamental and model plant, the branch development of petunia has always been a hot research topic. In our study, the homologous gene of SMALL LEAF AND BUSHY1 (SLB1) was isolated from Petunia ×hybrida cv. Mitchell Diploid. PhSLB1 contained a C-terminal WD40 repeat domain and an N-terminal F-box domain. An analysis of expression indicated that PhSLB exhibited the highest expression in roots, whereas expression levels were lowest in stems and leaves. Subcellular localization assays demonstrated that PhSLB1 was localized on the nucleus. Furthermore, RNA interference (RNAi) of PhSLB1 in petunia significantly increased the branch number. Quantitative real-time polymerase chain reaction showed that PhSLB1 not only regulated cytokinin and strigolactone pathway but also affected the expression of some key branching-related genes, such as PhBRC1, PhKNOX, PhH2A, and PhL27. Our research establishes a theoretical groundwork for revealing the mechanism by which SLB1 regulates branch development.

The stability of future carbon sinks is crucial for accurately predicting the global carbon cycle. However, the future dynamics and stability of carbon sinks remain largely unknown, especially in China, a significant global carbon sink region. Here, we examined the dynamics and stability of carbon sinks in China’s terrestrial ecosystems from 2015 to 2,100 under two CMIP6 scenarios (SSP245 and SSP585), using XGBoost and SHAP models to quantify the impact of climatic drivers on carbon sink stability. China’s future terrestrial ecosystems will act as a “carbon sink” (0.27–0.33 PgC/yr), with an initial increase that levels off over time. Although the carbon sink capacity increases, its stability does not consistently improve. Specifically, the stability of carbon sinks in future China’s terrestrial ecosystems transitions from strengthening to weakening, primarily occurring in areas with higher carbon sink capacity. Further analysis revealed that atmospheric vapor pressure deficit (VPD) and temperature (Tas) are the two primary factors influencing carbon sink stability, with significant differences in their impacts across different scenarios. Under the SSP245 scenario, variations in VPD (VPD.CV) regulate water availability through stomatal conductance, making it the key driver of changes in carbon sink stability. In contrast, under the SSP585 scenario, although VPD.CV still plays an important role, temperature variability (Tas.CV) becomes the dominant factor, with more frequent extreme climate events exacerbating carbon cycle instability. The study highlights the differences in driving factors of carbon sink stability under different scenarios and stresses the importance of considering these differences, along with the scale and stability of carbon sinks, when developing long-term carbon management policies to effectively support carbon neutrality goals.

Background Interleukin-18 (IL-18), or interferon (IFN)-γ-inducing factor, potentiates T helper 1 and natural killer cell activation as well as CD8+ T-cell proliferation. Recombinant IL-18 has displayed limited clinical efficacy in part due to the expression of the decoy receptor, IL-18 binding protein (IL-18BP). A series of IL-18 variants that are devoid of IL-18BP binding, termed DR18 (decoy-resistant IL-18), was developed via directed evolution. We tested DR18 using oncolytic adenovirus (oAd) as a platform for delivery in syngeneic mouse tumor models.Methods oAd harboring wild-type IL-18 or DR18 (oAdDR18) was constructed by inserting IL-18 mutant into modified oAd backbone with Ad5/3 chimeric fiber. The delivery effect and IFN-γ induction were determined by ELISA. The antitumor efficiency of oAdDR18 was tested in CT26, B16BL6 and 4T1 tumor-bearing mice, or athymic nude mice and compared with recombinant DR18 protein (rDR18). 4T1 lung metastasis model was used to evaluate the antitumor efficiency of local and distant tumors. Antitumor memory and synergistic effect with an anti-programmed cell death protein-1 (PD-1) antibody was evaluated. The phenotypes of the immune cells in tumor microenvironment were analyzed by flow cytometry and immunohistochemistry.Results Mice received oAdDR18 maintained stable production of IL-18 and IFN-γ compared with those received rDR18. Intratumoral delivery of oAdDR18 significantly reduced tumor growth across several tumor models, but not in the athymic nude mouse model. Mice that had tumor remission showed antitumor memory. The antitumor effect was associated with intratumor infiltration of CD4+ and CD8+ T cells. DR18 delivered by oAd demonstrated long-lasting and enhanced antitumor activities against local and distant tumors compared with that received rDR18 or wild-type IL-18 delivered by oAd (oAdwtIL-18). oAdDR18 treatment also reduced 4T1 lung metastasis. In addition, combination of this virotherapy with immune checkpoint inhibitors (ICIs)like the anti-PD-1 antibody further enhanced the antitumor activity as compared with respective monotherapy.Conclusions oAdDR18 demonstrates enhanced antitumor activities through the induction of stronger local and system immunities and modulation of the tumor microenvironment compared with those of oAdwtIL-18 and rDR18. A combination of oncolytic virotherapy with cytokine engineering would lead to cytokine-based therapeutics for cancer and other diseases.

Ecosystem water-use efficiency (WUE) is a crucial indicator for evaluating carbon and water cycles. Although greening and climate change have significantly altered the WUE in Chinese terrestrial ecosystems, the roles of physiological and ecological processes are not fully understood. To address this, WUE is broken down into two key ratios: gross primary productivity to transpiration (GPP/T), which mainly reflects the effect of plant physiological processes, and transpiration to evapotranspiration (T/ET), which primarily indicates the impact of vegetation changes. Both ratios are influenced by climate change. This study employed a newly developed satellite-based ecosystem service process model Carbon and Exchange between Vegetation, Soil, and Atmosphere-ecosystem service (CEVSA-ES) to examine the impact of GPP/T and T/ET on WUE in China's terrestrial ecosystems from 2000 to 2022, alongside an analysis of the environmental variables affecting these ratios. This study revealed a general increase in WUE during the study period with significant interdecadal differences. Between 2000 and 2010, WUE was relatively stable (slope = 0.0023 g C kg−1 H2O a−1, p > 0.05), primarily because the decrease in GPP/T (p 0.05). Factors affecting GPP/T and T/ET showed considerable variability. Precipitation had the main influence on GPP/T, accounting for 70 % of its variation. The initial decade of the 21st century experienced an overall precipitation deficiency, followed by a sustained surplus in the subsequent years, resulting in interdecadal fluctuations in GPP/T. In contrast, T/ET was affected by a combination of factors, including the leaf area index, temperature, and precipitation, contributing 39 %, 29 %, and 32 %, respectively. The present study advances our understanding of the interaction of terrestrial ecosystem with the atmosphere amid global changes, offering crucial insights for forecasting the future dynamics of carbon and water cycles.

Adoptive cell therapy (ACT) has revolutionized the treatment of patients with cancer. The success of ACT depends largely on transferred T cell status, particularly their less-differentiated state with stem cell-like properties, which enhances ACT effectiveness. Stem cell-like memory T (TSCM) cells exhibit continuous self-renewal and multilineage differentiation similar to pluripotent stem cells. TSCM cells are promising candidates for cancer immunotherapies, whereas maintenance of a more stem-cell-like state before transfer is challenging. Here, we established a highly efficient protocol for generating CD8+ TSCM cells from peripheral blood mononuclear cells (PBMCs). The process involved activating PBMCs using anti-CD3 monoclonal antibody and RetroNectin, followed by a transient-resting culture period (24 h) and subsequent long-term expansion in vitro with interlukien-2. We report that this transient-resting culture after activation preserves CD8+ T cells in a stem memory phenotype (CD95+ CD45RA+ CCR7+) compared to the conventional culture method. Further, this approach reduces the expression of T cell immunoglobulin mucin-3, an exhaustion marker, and increases the expression of T cell factor-1, a master regulator of stemness even after long-term culture compared to the conventional culture method. In conclusion, our study presents a simplified and cost-effective method for generating and expanding CD8+ TSCM cells ex vivo. This approach streamlines the optimization of cancer immunotherapy using ACT.

Objectives. The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. Methods. The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. Results. miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. Conclusion. Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.

Abstract Neoantigens derived from somatic mutations in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), the most frequently mutated oncogene, represent promising targets for cancer immunotherapy. Recent research highlights the potential role of human leukocyte antigen (HLA) allele A*11:01 in presenting these altered KRAS variants to the immune system. In this study, we successfully generate and identify murine T-cell receptors (TCRs) that specifically recognize KRAS8–16 G12V from three predicted high affinity peptides. By determining the structure of the tumor-specific 4TCR2 bound to KRASG12V-HLA-A*11:01, we conduct structure-based design to create and evaluate TCR variants with markedly enhanced affinity, up to 15.8-fold. This high-affinity TCR mutant, which involved only two amino acid substitutions, display minimal conformational alterations while maintaining a high degree of specificity for the KRASG12V peptide. Our research unveils the molecular mechanisms governing TCR recognition towards KRASG12V neoantigen and yields a range of affinity-enhanced TCR mutants with significant potential for immunotherapy strategies targeting tumors harboring the KRASG12V mutation.

Microrobots with different structures can exhibit multiple propulsion mechanisms under external magnetic fields. Swarms dynamically assembled by microrobots inherit the advantages of single microrobots, such as degradability and small dimensions, while also offering benefits like scalability and high flexibility. With control of magnetic fields, these swarms demonstrate diverse propulsion mechanisms and can perform precise actions in complex environments. Therefore, the relationship between single microrobots and their swarms is a significant area of study. This paper reviews the relationship between single microrobots and swarms by examining the structural design, control methods, propulsion mechanisms, and practical applications. At first, we introduce the structural design of microrobots, including materials and manufacturing methods. Then, we describe magnetic field generation systems, including gradient, rotating, and oscillating magnetic fields, and their characteristics. Next, we analyze the propulsion mechanisms of individual microrobots and the way microrobots dynamically assemble into a swarm under an external magnetic field, which illustrates the relationship between single microrobots and swarms. Finally, we discuss the application of different swarm propulsion mechanisms in water purification and targeted delivery, summarize current challenges and future work, and explore future directions.

Interannual variability (IAV) of terrestrial carbon uptake is a major contributor to the variation of atmospheric CO _2 . With the influence of the East Asian monsoon, future climate variability would significantly increase in China. However, how these future changes will modulate the IAV of China’s terrestrial carbon sinks remains unclear. Here, we analyzed the IAV of China’s terrestrial net ecosystem productivity (NEP _IAV ) and investigated the potential impacts of climate change under various scenarios during the 21st century using the outputs from nine Coupled Model Intercomparison Project Phase 6 models. The results reveal that China’s terrestrial NEP _IAV would be enhanced under higher emissions scenarios from 2015 to 2100. The standard deviation of national NEP _IAV under the SSP585 scenario rises by 12% compared with SSP126. The most prominent contribution to this enhancement in the total NEP _IAV comes from a larger NEP IAV in summer (10%), particularly in the subtropical–tropical monsoonal climate zone in China. Moreover, the enhancement is largely attributed to the intensified IAV in temperature and precipitation in the monsoonal climate zones as well as the heightened sensitivity to them, especially in the ecosystems of the subtropical–tropical monsoonal zone. Compared with monsoonal precipitation, IAV of temperature in the subtropical–tropical monsoonal climate zone also plays an important role in NEP _IAV under higher emissions scenarios. Our results highlight the crucial influence of future fluctuations in monsoon climate systems on terrestrial carbon sink IAV and the urgency of reducing the uncertainties of Earth system models in predicting both climate in monsoon regions and the responses of carbon cycling processes to temperature.

The human genome harbors many endogenous retroviral elements, known as human endogenous retroviruses (HERVs), which have been integrated into the genome during evolution due to infections by exogenous retroviruses. Accounting for up to 8% of the human genome, HERVs are tightly regulated by the host and are implicated in various physiological and pathological processes. Aberrant expression of HERVs has been observed in numerous studies on exogenous viral infections. In this review, we focus on elucidating the potential roles of HERVs during various exogenous viral infections and further discuss their implications in antiviral immunity.

ObjectiveTo assess the effectiveness and tolerability of both PD-1 and PD-L1 inhibitors in advanced cervical cancer (CC), focusing on varying PD-L1 levels.MethodsA comprehensive exploration was carried out on EMBASE, PubMed, Cochrane Library databases as well as Web of Science up to May 25, 2024, for studies involving advanced CC patients receiving PD-1/PD-L1 inhibitors. Inclusion criteria were studies reporting objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), as well as median overall survival (OS). Data extraction and quality assessment were performed by two reviewers using the JBI Case Series Critical Appraisal Checklist, followed by a meta-analysis via STATA/MP 16.0.ResultsFive eligible studies comprising 223 patients were chosen. ORR and DCR were 42% (95% CI: 17%-66%, P = 0.00) and 70% (95% CI: 22%-117%, P = 0.00), respectively, in the PD-L1 positive patients and were 36% (95% CI: 17%-54%, P = 0.00) and 47% (95% CI: 30%-63%, P = 0.00), respectively, in patients with PD-L1 negativity. For patients exhibiting PD-L1 positivity, median PFS and median OS were 3.98 months (95% CI: 0.80–7.16, P = 0.01) and 11.26 months (95% CI: 3.01–12.58, P = 0.00), respectively.ConclusionWith PD-1/PD-L1 inhibitors, PD-L1 positive CC patients demonstrate superior ORR, DCR, median PFS, and median OS, underscoring PD-L1 as one biomarker for immunotherapy response.

Abstract Background Immune‐checkpoint inhibitors are now used more commonly in combination than monotherapy as the first‐line choice in patients with unresectable advanced melanoma. Nevertheless, for cases that progressed after the initial combination therapy, the subsequent regimen option can be very difficult. Herein, we reported the efficacy and safety of a triple combination regimen in Chinese unresectable advanced melanoma patients who had poor responses to the first‐line immune therapy. Methods We reviewed the clinical profiles of patients diagnosed with stage IIIC‐IV melanoma between June 1, 2020, and September 30, 2023. The patients who failed the prior immune therapies and received anti‐PD‐1 mono antibody plus interferon(IFN)‐alpha 1b and anlotinib hydrochloride as the second‐line therapy were enrolled in the retrospective analysis. Additionally, we examined the exhaustion of T‐cells using mIHC staining in available tumor samples. Results Fifty‐five patients were included in this study. The median follow‐up period was 13.6 months. The objective response rate evaluated by the investigators was 9.1%(1CR, 4PR). The disease control rate was 47.3%. The median overall survival was 17.6 months, and the median progression‐free survival was 2.8 months. The adverse events rate of any grade was 100%. Grade 3 or 4 irAEs were observed in 29.1% of cases. Multiplex immunohistochemical staining revealed an increased trend of TIM3 expression on tumor‐infiltrating T cells in patients without objective response. Conclusion PD‐1 monoclonal antibody plus interferon‐alpha 1b plus anlotinib showed acceptable tolerability and anticancer benefits in Chinese metastatic melanoma patients as a second‐line therapy.

Abstract Ovarian cancer is the most lethal gynecologic neoplasm, and most patients experience recurrence and chemoresistance. Even the promising immunotherapy showed limited efficacy in ovarian cancer, probably due to the immunosuppressive microenvironment. However, the behind mechanisms of the immune exclusion or cold phenotype in ovarian cancer still remain to be explored. As a cancer dominated by copy number variations instead of mutations, ovarian cancer contains a high fraction of aneuploid, which might correlate with immune inhibition. Nevertheless, whether or how aneuploid affects ovarian cancer is still unclear. For exploring the role of aneuploid cancer cells and the potential ploidy-immune relationship, herein, the ploidy information was first comprehensively analyzed combining the karyotype data and copy number variation data obtained from Mitelman and cBioPortal databases, respectively. Ovarian cancer showed strong ploidy heterogeneity, with high fraction of aneuploid and recurrent arm-level and whole chromosome changes. Furthermore, clinical parameters were compared between the highly-aneuploid and the near-diploid ovarian cancers. Aneuploid indicated high grade, poor overall survival and poor disease-free survival in ovarian cancer. To understand the biofunction affected by aneuploid, the differentially expressed genes between the highly-aneuploid and the near-diploid groups were analyzed. Transcription data suggested that aneuploid cancer correlated with deregulated MHC expression, abnormal antigen presentation, and less infiltration of macrophages and activated T cells and higher level of T cell exclusion. Furthermore, the ploidy-MHC association was verified using the Human Protein Atlas database. All these data supported that aneuploid might be promising for cancer management and immune surveillance in ovarian cancer.

Abstract Full quantification of Positron Emission Tomography (PET) requires an arterial input function (AIF) for measurement of certain targets, or using particular radiotracers, or for the quantification of specific outcome measures. The AIF represents the measurement of radiotracer concentrations in the arterial blood plasma over the course of the PET examination. Measurement of the AIF is prone to error as it is a composite measure created from the combination of multiple measurements of different samples with different equipment, each of which can be sources of measurement error. Moreover, its measurement requires a high degree of temporal granularity for early time points, which necessitates a compromise between quality and quantity of recorded samples. For these reasons, it is often desirable to fit models to this data in order to improve its quality before using it for quantification of radiotracer binding in the tissue. The raw observations of radioactivity in arterial blood and plasma samples are derived from radioactive decay, which is measured as a number of recorded counts. Count data have several specific properties, including the fact that they cannot be negative as well as a particular mean-variance relationship. Poisson regression is the most principled modelling strategy for working with count data, as it both incorporates and exploits these properties. However, no previous studies to our knowledge have taken this approach, despite the advantages of greater efficiency and accuracy which result from using the appropriate distributional assumptions. Here, we implement a Poisson regression modelling approach for the AIF as proof-of-concept of its application. We applied both parametric and non-parametric models for the input function curve. We show that a negative binomial distribution is a more appropriate error distribution for handling overdispersion. Furthermore, we extend this approach to a hierarchical non-parametric model which is shown to be highly resilient to missing data. We thus demonstrate that Poisson regression is both feasible and effective when applied to AIF data, and propose that this is a promising strategy for modelling blood count data for PET in future.

As one lethal malignancy in women’s reproductive systems, ovarian cancer (OC) is frequently detected at an advanced phase during diagnosis. when the disease has spread widely. The absence of obvious symptoms and powerful screening tools in the early stages makes treatment difficult and the prognosis poor. Despite the clinical remission that can be achieved in some patients after initial treatment, the recurrence rate is conspicuous, posing a considerable challenge in treating recurrent OC (ROC). In the retrospective analysis, we compared the effects of two treatment regimens, aqupla combined with paclitaxel liposome (NP group) versus aqupla combined with docetaxel (ND group), on survival and biomarkers in patients with ROC. The study included 121 OC patients, and clinical data were collected through an electronic medical record system, outpatient review records, and a follow-up record system. The results revealed a notably higher overall remission rate in the ND group than the NP group, but revealed no notable inter-group discrepancy in toxicities, implying that the aqupla combined with docetaxel regimen may be more effective in platinum-sensitive ROC patients. Additionally, post-treatment CA125 levels were lower in patients in the ND group, suggesting that the regimen may be more effective in reducing tumour load. Survival analysis further revealed that treatment regimen, FIGO stage, number of recurrent lesions, and pretreatment CA125 level were independent prognostic factors affecting patients’ 5-year OS and PFS. Overall for ROC patients, especially platinum-sensitive patients, the aqupla in combination with docetaxel regimen provided an improved survival benefit with a comparable safety profile, highlighting the importance of individualised treatment strategies.

The purpose of the present study was to investigate the effects of different levels of a Chinese herbal medicine formulation combined with JM113 (CHM-JM113) on growth performance, antioxidant capacity, organ index, and intestinal health of AA broilers. The AA broiler chicks were randomly allocated to 5 treatments as follows: a basic diet for the control group, the basic diet supplemented with 0.25% CHM-JM113, 0.5% CHM-JM113, 1% CHM-JM113 and 2% CHM-JM113 for the treatment group, respectively. The results showed that the addition of CHM-JM113 to the diet significantly reduced the mortality (p 0.05). Comparing the control group, 0.5 and 1% CHM-JM113 group significantly improved the organ index of liver, spleen and bursa (p

Pediococcus acidilactici was mutated by space mutagenesis technology, and the strains with high production of exopolysaccharide (EPS) were screened. The functional characteristics of the EPS were also investigated. EPS production and genetic stability of the strains were measured, and a stable mutant strain L21-49 with high production of EPS was selected. Meanwhile, the self-aggregation and hydrophobicity of the mutant strain and the original strain were investigated, and the tolerances of the strains to acid, bile salts, and artificial simulated gastrointestinal fluid were compared. The anti-biofilm, anti-oxidant, and the inhibitory activities on α-amylase and α-glucosidase of EPS were also analyzed. The results showed that the EPS yield of the mutant strain was 196.23 mg/L, which was 26.54% higher than that of the original strain L21. The strain showed good self-aggregation, hydrophobicity and tolerance in vitro. The viable cell number could be maintained at 107 CFU/mL after being cultured in pH2.0 and 3.0 for 3 h. When treated with 4.00 g/L bile salt for 24 h, the number of viable cells were 107 CFU/mL. The viable count could be maintained at 106 CFU/mL after the treatment of the artificial simulated gastrointestinal fluid. The EPS presented good antioxidant capacity in vitro. When the concentration of EPS was 8.0 mg/mL, the clearance rates on DPPH, OH, ABTS+ and \begin{document}${\rm{O}}_2^- $\end{document} were 91.75%, 38.44%, 54.71% and 58.84%, respectively. The inhibition rates of L21-49 EPS on the biofilms of Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Pseudomonas aeruginosa were 40.04%, 60.04%, 50.59% and 33.68%, respectively. It inhibited the activities of α-amylase and α-glucosidase by 23.52% and 51.15%, respectively. In this study, the effects of space mutagenesis on the probiotic characteristics and EPS production of lactic acid bacteria were investigated, so as to provide reference for the research and development of lactic acid bacteria and the EPS.

Foodborne pathogen is an important factor affecting food safety. With the biotechnology development and the improved requirements for food safety, the detection methods of foodborne pathogens are constantly updated and improved. By microfluidic technology, the processes of sample pretreatment, separation and detection are integrated on a tiny chip, and a variety of functions are completed. As an important branch, droplet microfluidic technology can be used for high-throughput detection with the dispersed microdroplets formed by two insoluble liquids. In this paper, according to the different ways of nucleic acid amplification, the characteristics of droplet microfluidic-digital polymerase chain reaction, droplet microfluidic-digital loop-mediated isothermal amplification, and droplet microfluidic-digital recombinase polymerase amplification are compared and summarized. The applications of these methods in the detections of foodborne pathogens are also presented. In addition, the future developments of these technologies are prospected. The intelligent, continuous, precise and miniaturized rapid detections of foodborne pathogens are realized by droplet microfluidic technology combined with digital nucleic acid amplification. This paper would provide references for the development of the technology in the field of rapid detection of foodborne pathogens.

In plant-pathogen interactions, Magnaporthe oryzae causes blast disease on more than 50 species of 14 monocot plants, including important crops such as rice, millet, and most 15 recently wheat. M. oryzae is a model fungus for studying plant-microbe interaction, and the main source for fungal pathogenesis in the field. Here we report that MoJMJD6 is required for conidium germination and appressorium formation in M. oryzae. We obtained MoJMJD6 mutants (ΔMojmjd6) using a target gene replacement strategy. The MoJMD6 deletion mutants were delayed for conidium germination, glycogen, and lipid droplets utilization and consequently had decreased virulence. In the ΔMojmjd6 null mutants, global histone methyltransferase modifications (H3K4me3, H3K9me3, H3K27me3, and H3K36me2/3) of the genome were unaffected. Taken together, our results indicated that MoJMJD6 function as a nuclear protein which plays an important role in conidium germination and appressorium formation in the M. oryzae. Our work provides insights into MoJMJD6-mediated regulation in the early stage of pathogenesis in plant fungi.

Corn silage is the main feed in the diet of dairy cows and other ruminant livestock. Silage corn feed is very susceptible to spoilage and corruption due to the influence of aerobic secondary fermentation during the silage process. At present, silage quality testing of corn feed mainly relies on the combination of sensory evaluation and laboratory measurement. The sensory review method is difficult to achieve precision and objectivity, while the laboratory determination method has problems such as cumbersome testing procedures, time-consuming, high cost, and damage to samples. In this study, the external sensory quality grading model for different qualities of silage corn feed was established using hyperspectral data. To explore the feasibility of using hyperspectral data for external sensory quality grading of corn silage, a hyperspectral system was used to collect spectral data of 200 corn silage samples in the 380–1004 nm band, and the samples were classified into four grades: excellent, fair, medium, and spoiled according to the German Agricultural Association (DLG) standard for sensory evaluation of silage samples. Three algorithms were used to preprocess the fodder hyperspectral data, including multiplicative scatter correction (MSC), standard normal variate (SNV), and S–G convolutional smoothing. To reduce the redundancy of the spectral data, variable combination population analysis (VCPA) and competitive adaptive reweighted sampling (CARS) were used for feature wavelength selection, and linear discriminant analysis (LDA) algorithm was used for data dimensionality reduction, constructing random forest classification (RFC), convolutional neural networks (CNN) and support vector machines (SVM) models. The best classification model was derived based on the comparison of the model results. The results show that SNV-LDA-SVM is the optimal algorithm combination, where the accuracy of the calibration set is 99.375% and the accuracy of the prediction set is 100%. In summary, combined with hyperspectral technology, the constructed model can realize the accurate discrimination of the external sensory quality of silage corn feed, which provides a reliable and effective new non-destructive testing method for silage corn feed quality detection.

Using swine manure biochar and biogas slurry in agriculture proves to be an effective strategy for soil improvement and fertilization. In this study, a pot trial on the growth of lotus root was conducted to investigate the persistent effects of applying 350°C swine manure biochar (1% and 2%) and biogas slurry (50% and 100%) on soil nitrogen nutrient and lotus root quality. The results showed that compared to chemical fertilizer alone (A0B0), swine manure biochar significantly increased soil nitrogen content after one year of application. The contents of total nitrogen (TN), alkali-hydrolyzed nitrogen (AHN), ammonium nitrogen (NH4+-N), and nitrate nitrogen (NO3− −N) increased by 17.96% to 20.73%, 14.05% to 64.71%, 17.76% to 48.68% and 2.22% to 8.47%, respectively, during the rooting period. When swine manure biochar was present, the application of biogas slurry further elevated soil nitrogen content. The co-application of swine manure biochar and biogas slurry significantly increased soil nitrogen content, and the 100% nitrogen replacement with biogas slurry combined with 2% swine manure biochar (A2B2) treatment exhibited the most significant enhancement effect during whole plant growth periods. Soil enzyme activities, including soil protease (NPT), leucine aminopeptidase (LAP), b-glucosidase (β-GC) and dehydrogenase (DHA), showed a tendency to increase and then decrease with the prolongation of lotus root fertility period, reaching the maximum value during the rooting period. Compared to A0B0, the treatment with 2% swine manure biochar had the most significant effect on enzyme activities and increased the lotus root’s protein, soluble sugar, and starch contents. Nitrate content decreased with the application of 2% swine manure biochar as the amount of biogas slurry increased. In conclusion, swine manure biochar effectively improved soil nitrogen content, enzyme activity, and lotus root quality. Even after one year of application, 2% swine manure biochar had the best enhancement effect.

Meropenem is an ultrabroad-spectrum antimicrobial agent that is often recommended for the treatment of bacterial meningitis (BM) in children. However, a subtherapeutic phenomenon occurred in BM children complicated with augmented renal clearance (ARC) at the recommended dose of meropenem. To support its pharmacokinetics, a sensitive, fast and robust ultra-liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed to measure meropenem concentrations in serum and cerebrospinal fluid (CSF). The method involved protein precipitation, and samples were diluted with a large proportion of water to eliminate solvent effects. The separation of samples was performed on a Waters Acquity™ BEH C18 column (2.1 × 50 mm i.d., 1.7 μm) with a gradient profile. The mobile phases were formic acid–water (1:1000, v/v) and acetonitrile. The linear range was good, with a concentration range of 0.100–100 μg/mL for serum and 0.0400–20.0 μg/mL for CSF. The intra-day and inter-day precisions were less than 8.0%, and the intra-day and inter-day accuracies varied −6.6% from 6.5% for the both serum and CSF. The selectivity, carry-over, dilution integrity, matrix effect, recovery and stability were validated according to international guidelines. The developed UPLC–MS/MS method successfully determined the meropenem concentrations in the serum and CSF of children with BM complicated with ARC. The results indicated that under the recommended dosing regimen (40 mg/kg every 8 h), the time to reach the effective treatment target of 50%T > MIC was only approximately 3 h and lower CSF concentrations of meropenem were observed in children with BM with ARC.

With increasing global awareness of soil health, attention must be paid to fluorine exposure in soils, which poses a threat to human health. Therefore, this study aimed to study the fluorine adsorption characteristics of swine manure and straw biochars and their impact on fluorine adsorption-desorption in soil with batch experiments. The biochar samples originated from high-temperature anaerobic cracking of swine manure (350°C, 500°C, and 650°C) and straw (500°C). Results indicated that the adsorption of soil fluorine reached adsorption equilibrium at around 4 h after the mixing of swine manure and straw biochar. Fluorine adsorption kinetics using these biochars conformed to the quasi-two-stage kinetic model. The fluorine adsorption kinetics for biochar-treated soils conformed to the double-constant equation and the Elovich equation, and the soil treated with straw biochar showed the fastest fluorine adsorption rate. The adsorption isotherms of fluorine for biochars and biochar-treated soils could be fitted by the isothermal adsorption model of Langmuir and Freundlich. The maximal equilibrium quantity of fluorine was 73.66 mg/g for swine manure biochar. The soil, adding with 2% of swine manure biochar achieved with showed at 650°C had the smallest adsorption. This study also shows that the adsorption of fluorine by biochar gradually decreased with the increase of pH. Comparing with other factors, the mixture pH with biochars added had a significant effect on fluorine adsorption. The decreased fluorine adsorption capacities for soils treated with swine manure and straw biochars were closely related to the increased pH in soils after adding biochars. Considering the fluorine threat in soil, this study provides a theoretical basis for the application of biochars on soil fluorine adsorption.

Abstract Adipose derived stem cells (ADSCs) are popular in regenerative medicine due to their easy availability, low immunogenicity and lack of controversy regarding their ethical debate use. Although ADSCs can repair nerve damage, the oxidative microenvironment of damaged tissue can induce apoptosis of transplanted stem cells, which weakens the therapeutic efficacy of ADSCs. Resveratrol (Res) is a type of natural polyphenol compound that regulates the proliferation, senescence and differentiation of stem cells. Therefore, we investigated whether incubation of ADSCs with Res improves their to promote peripheral nerve regeneration. ADSCs were cultured in vitro and treated with H2O2 to establish an apoptosis model. The control, H2O2 and Res groups were set up. The cell survival rate was detected by the CCK-8 method. The TUNEL assay was used to detect the apoptosis of the cells. qRT‒PCR was used to analyze the expression of apoptosis-related mRNA, and the effect of Res on the proliferation of ADSCs was investigated. In vivo, 40 SD rats were randomly divided into the control, model, ADSCs and ADSC + Res groups, with 13 rats in each group. The sciatic nerve injury rat model was established by the clamp method. Gait was observed on Days 7, 14, 21, and 28. Sciatic nerve regeneration was detected on Day 28. Res had no effect on the proliferation of ADSCs, and the TUNEL assay confirmed that Res pretreatment could significantly improve H2O2-induced apoptosis in ADSCs. Compared with the control group, caspase-3, Bax and Bcl-2 expression levels were significantly increased in the H2O2 group. Compared with the H2O2 group caspase-3 and Bax expression levels were significantly decreased, and Bcl-2 expression levels were significantly increased in ADSCs + Res group. At 4 weeks after surgery, the functional index of the sciatic nerve in the ADSCs + Res group was significantly higher than that in the model group. On Day 28, the average density of the sciatic nerve myelin sheath in the ADSCs + Res group was significantly increased compared with that in the model group, and Nissl staining showed that the number of motor neurons in the spinal cord was significant compared with that in the model group. Compared with the control group, the wet weight ratio of gastrocnemius muscle and muscle fiber area in ADSCs + Res group were significantly increased. Res enhanced the ability of ADSCs to promote sciatic nerve regeneration in rats.

The lactic acid bacteria (LAB) strains that inhibited the quorum sensing (QS) and biofilm formation of Vibrio parahaemolyticus were screened and their probiotic properties were studied. The effects of quenching the QS and inhibiting biofilm formation of V. parahaemolyticus of ten strains of LAB were determined by Vibrio harveyi BB170 bioluminescence assay and crystal violet staining method. Furthermore, the self-aggregation, coagulation, hydrophobicity, biofilm formation ability and antibacterial spectrum were analyzed. The results showed that there were significant differences in the inhibitory effects of ten strains on the biofilm formation of V. parahaemolyticus, and the inhibitory effects of the strains on AI-2 activities were correlated with those on biofilm formation of V. parahaemolyticus. The inhibition rates of A10 strain on the AI-2 and biofilm of V. parahaemolyticus were 82.92% and 87.70%, respectively. B11 and L18 strains that promoted the activity of AI-2 had no inhibitory effect on biofilm formation. The self-aggregation rate and hydrophobic rate of MS1 strain were both above 80%, and the biofilm-forming ability was strong. Moreover, MS1 strain exhibited obvious inhibitory effects on the QS and biofilm formation of V. parahaemolyticus, the inhibition rates were 69.54% and 77.32% respectively, with strong antibacterial effect. This study would provide reference for the research and development of LAB derived QS inhibitors, and has positive significance for the full utilization of LAB resources.

Coal gangue is a by-product of the production of coal-associated minerals, and belongs to bulk solid waste material. coal gangue concrete is an important practice for its resource utilization. Carbon neutrality and carbon peaks require all industries to make corresponding plans for the sustainable development of green ecology. In terms of resource utilization of building materials, coal gangue was used as aggregates to develop high-performance concrete, which started a new material innovation in the construction and civil engineering industries. At the same time, it can accelerate the process of carbon neutralization as the backbone of the indispensable treatment of low-carbon resources. Scholars at home and abroad have done a lot of theoretical and experimental research on the mechanical properties and engineering application of coal gangue concrete, and have made significant progress in improving the performance of coal gangue concrete, engineering practical application and production technology innovation, and established a relatively complete research system. Based on the differences in chemical and physical properties of coal gangue in different regions, this paper elaborates on the mechanical and durability properties of coal gangue concrete prepared with different aggregates, analyzes the feasibility and current research limitations of coal gangue application in civil engineering, and looks forward to the resource utilization prospects of coal gangue as aggregate to prepare new concrete in road engineering and building structures, provide a new perspective and reference for the large-scale recycling and utilization of coal gangue and further research on coal gangue concrete.

Marine target detection and recognition depend on the characteristics of marine targets and sea clutter. Therefore, understanding the essential features of marine targets based on the measured data is crucial for advancing target detection and recognition technology. To address the issue of insufficient data on the scattering characteristics of marine targets, the Sea-Detecting Radar Data-Sharing Program (SDRDSP) was upgraded to obtain data on marine targets and their environment under different polarizations and sea states. This upgrade expanded the physical dimension of radar target observation and improved radar and auxiliary data acquisition capabilities. Furthermore, a dual-polarized multistate scattering characteristic dataset of marine targets was constructed, and the statistical distribution characteristics, time and space correlation, and Doppler spectrum were analyzed, supporting the data usage. In the future, the types and quantities of maritime targets will continue to accumulate, providing data support for improving marine target detection and recognition performance and intelligence.

Objective Peritoneal dialysis (PD) requires high patient conscientiousness. Therefore, we aimed to investigate the relationship between conscientiousness score and prognosis in PD patients.Methods The ten-item Big Five Personality Inventory’s Chinese version was used to assess the conscientiousness score. Basic clinical information, prior medical history, hematological examination results, the occurrence of the first peritonitis and catheter-related infection, the start of hemodialysis, and the time of renal transplantation were collected. The patients were split into two groups, high and low conscientiousness groups, based on the mean value of the conscientiousness score. The differences in prognostic indicators were compared between groups, and the association between conscientiousness score and prognostic indicators in PD patients was assessed.Results Enrolled PD patients were divided into low conscientiousness group 103 and high conscientiousness group 98. There were significant differences in serum albumin (p = 0.021) and iPTH (p = 0.045) between the two groups. Multivariate Cox regression analysis identified conscientiousness score as an independent risk factor for the development of first peritonitis (HR = 0.558, 95% CI 0.400–0.779, p = 0.001) and first catheter-related infection (HR = 0.544, 95% CI 0.308–0.962, p = 0.036) in PD patients. Conscientiousness score (HR = 2.377, 95% CI 1.109–5.095, p = 0.026) was independently associated with renal transplantation.Conclusion Conscientiousness personality is closely related to the prognosis of PD patients.

Porcine circovirus type 2 (PCV2) infection can cause immunosuppressive diseases in pigs. Vascular endothelial cells (VECs), as the target cells for PCV2, play an important role in the immune response and inflammatory regulation. Endothelial IL-8, which is produced by porcine hip artery endothelial cells (PIECs) infected with PCV2, can inhibit the maturation of monocyte-derived dendritic cells (MoDCs). Here, we established a co-culture system of MoDCs and different groups of PIECs to further investigate the PCV2-induced endothelial IL-8 signaling pathway that drives the inhibition of MoDC maturation. The differentially expressed genes related to MoDC maturation were mainly enriched in the NF-κB and JAK2-STAT3 signaling pathways. Both the NF-κB related factor RELA and JAK2-STAT3 signaling pathway related factors (IL2RA, JAK, STAT2, STAT5, IL23A, IL7, etc.) decreased significantly in the IL-8 up-regulated group, and increased significantly in the down-regulated group. The expression of NF-κB p65 in the IL-8 up-regulated group was reduced significantly, and the expression of IκBα was increased significantly. Nuclear translocation of NF-κB p65 was inhibited, while the nuclear translocation of p-STAT3 was increased in MoDCs in the PCV2-induced endothelial IL-8 group. The results of treatment with NF-κB signaling pathway inhibitors showed that the maturation of MoDCs was inhibited and the expression of IL-12 and GM-CSF at mRNA level were lower. Inhibition of the JAK2-STAT3 signaling pathway had no significant effect on maturation, and the expression of IL-12 and GM-CSF at mRNA level produced no significant change. In summary, the NF-κB signaling pathway is the main signaling pathway of MoDC maturation, and is inhibited by the PCV2-induced up-regulation of endothelial-derived IL-8.

Abstract Abnormal coagulation and increased risk of thrombosis are some of the symptoms associated with COVID-19 severity. Anti-phospholipid antibodies (aPLs) present in critically ill COVID-19 patients contribute to systemic thrombosis. The aim of this study was to identify key common genes to characterize genetic crosstalk between COVID-19 and antiphospholipid syndrome (APS) using bioinformatics analysis and explore novel mechanisms of immune-mediated thrombosis in critically ill COVID-19 patients. The transcriptome data of mononuclear cells from severe COVID-19 patients and APS patients were evaluated to obtain the common genes. The protein–protein interaction network and cytoHubba module analysis in Cytoscape software were used to find the associated hinge genes and hub genes. Among the common differentially expressed genes, TIMELESS depletion was identified only in patients with severe COVID-19 and not in patients with mild COVID-19, and it was validated with the GSE159678 dataset. Functional analyses using gene ontology terms and the Kyoto Encyclopedia of Genes and Genomes pathway suggested that TIMELESS might contribute to the production of antiphospholipid antibody and thrombosis in both COVID-19 and APS patients. The potential role of TIMELESS and autophagy genes in momonuclear cells were further investigated, and GSK3B was found to be associated with TIMELESS. Autophagy targeting agents have a therapeutic potential against COVID-19 and thrombogenesis in APS, which may be related to the role of autophagy genes in the modification of circadian clock proteins. Interference with TIMELESS and other genes associated with it to regulate autoantibody expression may be a potential strategy for immunotherapy against thrombogenesis in severe COVID-19 patients.

The world is facing an ever-growing global energy crisis with unprecedented depth and complexity. The sustainable development of high energy density lithium-ion batteries for electric vehicles and portable electric devices has become a feasible way to deal with this problem. Silicon suboxides (SiOx) have been deemed as one of the most promising anode materials because of their ultrahigh theoretical lithium storage capacity, proper working potential, natural abundance, and environmental friendliness. However, the mass utilization of SiOx-based anodes is severely obstructed by their low electrical conductivity and inevitable volume expansion. While lithium silicate and lithium oxide formed in the first lithiation process act as buffer layers to some extent, it is urgent to address the accompanying low initial Coulombic efficiency and unsatisfactory cycling stability. In this review, we summarized recent advances in the synthesis methods of SiOx-based materials. Besides, the benefits and shortcomings of the various methods are briefly concluded. Then, we discussed the effective combination of SiOx with carbon materials and designs of porous structure, which could considerably enhance the electrochemical performance in detail. Furthermore, progresses on the modified strategies, advanced characteristics and industrial applications for SiOx-based anodes are also mentioned. Finally, the remaining challenges encountered and future perspectives on SiOx-based anodes are highlighted.

The karst region of southwest China showed a significant increase in vegetation cover and vegetation carbon stocks under the implementation of a series of ecological restoration projects. However, the relative contribution of ecological restoration projects to terrestrial carbon sequestration in the context of climate change has yet to be well quantified. Here, we used the Community Land Model (CLM4.5) to investigate the trend of net ecosystem productivity (NEP) and attribution to multiple environmental factors in the karst region of southwest China during 2000–2018. The result showed that ecosystems with a significant increasing trend of NEP covered about 46% of the study region, which were mainly located in the peak forest plain region, colliculus region, peak cluster depression region, and middle-high hill region. The simulation experiments suggested that land use change associated with ecological restoration projects caused a large contribution of 53% to the increasing NEP trend, followed by CO2 fertilization (72%), while climate factors and nitrogen deposition showed minor negative effects. Especially, the NEP trend induced by land use change in the 100 pilot counties with the implementation of rocky desertification control project was significantly higher than that in the other karst area. Moreover, moderate and high levels of restoration efforts invested into recovery led to a larger increasing trend (0.66 gC/m2/yr2 and 0.48 gC/m2/yr2) in NEP than the low efforts level (0.22 gC/m2/yr2). Our results highlight the important role of ecological restoration projects in the enhanced terrestrial carbon sequestration in the karst region of southwest China, and recommend a comprehensive assessment of ecological restoration projects for policymaking.

Modern sensor networks—those used for autonomous driving, security systems, human motion tracking, or smart city/smart factory applications—are shifting to a more centralized data processing approach to enable efficient multimodal sensor fusion for optimal environment perception in complex dynamic situations. Among lidars and cameras, radars are typical for these applications, but they generate huge amounts of data, which cannot be transmitted or stored effectively in current setups. Consequently, manufacturers usually have to process the data “on sensor.” This results in transmitting only a few extracted features as point clouds or object lists to a central processing unit, which usually causes a significant loss of information. With this approach, advanced processing—such as enhancement of resolution by coherent combination of sensors or ghost target removal with advanced algorithms—is hardly possible. To overcome this, we suggest an alternative method by using signal-based compression with defined losses. The following topology will be proposed: the sensors encode raw data without prior radar-specific processing and after transmission, a central unit decodes and processes the radar data, thus benefiting from its more powerful heterogeneous processing system. We will analyze lossless compression algorithms with rate savings of about 30% to 65%, but the focus is on lossy compression algorithms that incorporate higher compression ratios by allowing negligible errors. It is shown that state-of-the-art multimedia compression algorithms can obtain rate savings of 99%, and radar specific algorithms can add a 50-fold gain on top, reaching 99.98%. To assess the distortions of compressed data, we then present different radar-specific evaluation metrics.

Most studies on supply chain coordination assume that consumers are rational. However, with the development of e-commerce, consumer-bounded rationality has become an important issue with respect to supply chain coordination. Based on the assumption that some consumers are loyal to the offline shop and others are reference-dependent, this article examines the mechanism of vertical restraints and their competitive effects. This research study found that compared with the assumption of rational consumers used in previous literature, vertical restraints help internalize the “channel price gap externality” when consumers are loss averse. When separately operating, the offline shop will set a higher price due to its consumers’ higher loyalty and willingness to pay. However, given the positive externality of this price to the online retail sales, the offline price is still lower than the level under vertical integration. When the upstream manufacturer achieves supply chain coordination with vertical restraint contracts, the channel price gap externality is internalized, and the channel price gap expands to stimulate loss-averse consumers’ purchasing decisions.

Chemical epigenetic cultivation of the sponge-derived fungus Pestalotiopsis sp. SWMU-WZ04-1 contributed to the identification of twelve polyketide derivatives, including six new pestalotiopols E–J (1–6) and six known analogues (7–12). Their gross structures were deduced from 1D/2D NMR and HRESIMS spectroscopic data, and their absolute configurations were further established by circular dichroism (CD) Cotton effects and the modified Mosher’s method. In the bioassay, the cytotoxic and antibacterial activities of all compounds were evaluated. Chlorinated benzophenone derivatives 7 and 8 exhibited inhibitory effects on Staphylococcus aureus and Bacillus subtilis, with MIC values varying from 3.0 to 50 μg/mL. In addition, these two compounds were cytotoxic to four types of human cancer cells, with IC50 values of 16.2~83.6 μM. The result showed that compound 7 had the probability of being developed into a lead drug with antibacterial ability.

Reliable and fast active reset protocols are key to the functioning of quantum computing systems. Here, the authors use parametric driving to swap an excitation from a transmon qubit to its readout resonator within 34 ns, with negligible effects on neighboring qubits.

Abstract Background As a biennial plant, Secale cereale L is usually harvested in the autumn in the northern part of China where the temperature difference between day and night is of great disparity Through the pot experiment, the seedlings were cut to 2, 6 and 10 cm stubble height, and the simulated freeze-thaw (FT) stress (10/− 5 °C) was carried out after 6 days regrowth. The physiological effects of FT with different stubble height were revealed by analyzing the relative water content (RWC), osmotic adjustment substance concentration (soluble sugar and protein), membrane peroxidation (MDA) and catalase (CAT) activity. Results The results demonstrated that under freeze stress (− 5 °C), the content of soluble protein and MDA decreased and the seedlings of 2 cm treatment kept higher level of soluble protein and MDA, while the seedlings of 6 and 10 cm treatments kept higher level of the RWC, soluble sugar content, and CAT activity. After FT stress, the content of soluble sugar and protein, RWC in the 6 cm treatment were higher than those in 2 cm and 10 cm treatments, and the CAT activity in 10 cm treatment was the highest while the MDA content is lower. Conclusion These data suggest that keeping high stubble height is more adaptive for short-term FT stress.

The resistance and recovery rate of forest ecosystems to droughts vary with the severity of the drought. Studies on the impacts of severe droughts on forest ecosystems have suggested that evergreen forests have higher resistance than deciduous forests. However, whether the resistance and recovery rate of forest ecosystems vary under moderate droughts remained largely unknown. Here, we used the Standardized Precipitation Index to identify drought characteristics in China’s forest ecosystems from 2000 to 2018. We quantified the resistance and recovery rate to moderate droughts under different drought timings based on the Enhanced Vegetation Index. We then adopted random forest regression to evaluate the relative importance of climatic variables and species richness as drivers of resistance and recovery rate to moderate droughts. We found that China’s forest ecosystems mainly experienced moderate drought events, resulting in different resistance and recovery rate compared to severe droughts. Deciduous forests had high resistance (30.39 ± 21.32) and evergreen forests had high recovery rate (1.38 ± 1.10) due to their different response strategies under moderate droughts. The resistance and recovery rate of China’s forest ecosystems varied under different drought timings. The differences between deciduous and evergreen forests’ resistance (43.88 – 78.24 %) and recovery rate (-31.04 – −52.20 %) were remarkable in spring, autumn, and winter. In evergreen and deciduous forests, climatic variables were the main influencing factors of resistance and recovery rate to moderate droughts, similar to the leading role of climatic variables under severe droughts. Global radiation (41.06 %) and temperature (30.97 %) were the dominant factors contributing to resistance, whereas the recovery rate was primarily explained by global radiation (40.30 %) and precipitation (27.33 %). Thus, the high resistance in deciduous forests and the high recovery rate in evergreen forests under moderate droughts suggest that evergreen and deciduous forests can be mixed to improve the stability of forest ecosystems under climate change.

Abstract The umbilical–portal venous system (UPVS) plays an important role in embryonic development, as well as a significant blood circulation system to ensure the normal blood supply of fetal heart and brain and other vital organs. Congenital anomalies of UPVS contain many subtypes with a broad spectrum of manifestations and prognoses. Furthermore, because of fetal small lumen of UPVS, the sonographic evaluation remains difficult in utero. Appreciation of normal embryology and anatomy of UPVS is essential to an understanding of sonographic characteristics of anomalies of UPVS and fetal sequential changes. Through reviewing previous references and our experience with congenital abnormalities of UPVS, a new comprehensive classification is proposed. The new classification identifies three types of congenital abnormalities of UPVS based on morphological abnormalities and shunts. The embryology and etiology, sonographic, clinical and prognostic characteristics of each subtype of the new classification are described in detail. Knowledge of congenital abnormalities of UPVS can give sonographers a clue and aid prenatal sonographic diagnosis. The purpose of this article is to help the sonographers to understand the new classification of congenital abnormalities of UPVS, master the sonographic characteristics of each subtype and prenatal ultrasonographic screening strategy, and guide subsequent appropriate counseling and management.