How Labor Costs Affect Innovation Output in Pharmaceutical Companies: Evidence from China.

Existing literature generally suggests that rising labor costs lead to the substitution of capital for labor, prompting firms to save on labor costs through technological upgrades. However, as a typical human capital-intensive industry, the pharmaceutical sector finds it challenging to replace labor with capital through the introduction of advanced equipment. Therefore, compared to other industries, the pharmaceutical sector faces greater adverse impacts. Research on how pharmaceutical R&D behavior is influenced by labor costs is scarce. This paper analyzes the triple effects of rising labor costs on corporate innovation from the perspectives of human capital, physical capital, and financial capital. Based on empirical research using data from Chinese listed companies, we found that an increase in labor costs promotes innovation output in the pharmaceutical sector, but this effect is more pronounced in other sectors. Financing constraints play a negative role on corporate innovation in the pharmaceutical sector, while it is not significant in the other sectors. Factor substitution play a positive effect on corporate innovation in the other sectors, which is invalid in the pharmaceutical sector. This research contributes to a deeper understanding of the unique mechanisms by which labor costs impact innovation activities in the pharmaceutical industry.

Hindrance or facilitator? The economic consequences of national demonstration eco-industrial parks in China.

Many countries attach great importance to the green, low-carbon, and circular development of industrial parks. China is one of them and has entered an exploration journey of national demonstration eco-industrial parks (NDEIPs). However, the impact of the transformation of industrial parks into NDEIPs on local economic development still remains a mystery. To address this issue, we develop an empirical study using a combination of the multi-period difference-in-differences method and the propensity score matching method based on the panel data for 266 cities in China from 2001 to 2021. The results show that industrial parks becoming NDEIPs promotes cities' economic development. This conclusion still holds after a series of robustness tests, such as the reverse causality test and the placebo test. Moreover, the park heterogeneity tests show that the economic consequences vary according to differences in levels, industry types, life cycle phases, and the degree of foreign firm agglomeration. The city heterogeneity tests show that the economic consequences differ based on administrative levels, innovation capabilities, technology industrialization, and environmental friendliness. The spatial heterogeneity tests show that the economic consequences differ according to geographical location and whether situated in the Yangtze River Economic Belt. The policy upgrading heterogeneity tests show that the economic consequences differ during the process of policy upgrading and transformation. In addition, the mechanism tests reveal that green innovation, human capital level, and firm attractiveness mediate the relationship between industrial parks becoming NDEIPs and cities' economic development. This study provides a new perspective for understanding the economic effects of the transformation of industrial parks into NDEIPs, and provides a reference for the government on how to maximize these economic effects.

Bioinformatic Identification of Signaling Pathways and Hub Genes in Vascular Dementia.

BACKGROUND: Vascular dementia (VaD) is a prevalent neurodegenerative disease characterized by cognitive impairment due to cerebrovascular factors, affecting a significant portion of the aging population and highlighting the critical need to understand specific targets and mechanisms for effective prevention and treatment strategies. We aimed to identify pathways and crucial genes involved in the progression of VaD through bioinformatics analysis and subsequently validate these findings. METHODS: We conducted differential expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and Protein-Protein Interaction (PPI) analysis. We utilized pheochromocytoma 12 (PC12) cells to create an in vitro oxygen-glucose deprivation (OGD) model. We investigated the impact of overexpression and interference of adrenoceptor alpha 1D (ADRA1D) on OGD PC12 cells using TdT-mediated dUTP nick-end labeling (TUNEL), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot (WB), and Fluo-3-pentaacetoxymethyl ester (Fluo-3 AM) analysis. RESULTS: We found 187 differentially expressed genes (DEGs) in the red module that were strongly associated with VaD and were primarily enriched in vasoconstriction, G protein-coupled amine receptor activity, and neuroactive ligand-receptor interaction, mitogen-activated protein kinase (MAPK) signaling pathway, and cell adhesion. Among these pathways, we identified ADRA1D as a gene shared by vasoconstriction, G protein-coupled amine receptor activity, and neuroactive ligand-receptor interaction. The TUNEL assay revealed a significant decrease in PC12 cell apoptosis with ADRA1D overexpression (p < 0.01) and a significant increase in apoptosis upon silencing ADRA1D (p < 0.01). RT-qPCR and WB analysis revealed elevated ADRA1D expression (p < 0.001) and decreased phospholipase C beta (PLCß) and inositol 1,4,5-trisphosphate receptor (IP3R) expression (p < 0.05) with ADRA1D overexpression. Moreover, the Fluo-3 AM assessment indicated significantly lower intracellular Ca2+ levels with ADRA1D overexpression (p < 0.001). Conversely, interference with ADRA1D yielded opposite results. CONCLUSION: Our study provides a new perspective on the pathogenic mechanisms of VaD and potential avenues for therapeutic intervention. The results highlight the role of ADRA1D in modulating cellular responses to OGD and VaD, suggesting its potential as a target for VaD treatment.

CRISPR-Cas9 screening identifies INTS3 as an anti-apoptotic RNA-binding protein and therapeutic target for colorectal cancer.

Growing evidences indicate that RNA-binding proteins (RBPs) play critical roles in regulating the RNA splicing, polyadenylation, stability, localization, translation, and turnover. Abnormal expression of RBPs can promote tumorigenesis. Here, we performed a CRISPR screen using an RBP pooled CRISPR knockout library and identified 27 potential RBPs with role in supporting colorectal cancer (CRC) survival. We found that the deletion/depletion of INTS3 triggered apoptosis in CRC. The in vitro experiments and RNA sequencing revealed that INTS3 destabilized pro-apoptotic gene transcripts and contributed to the survival of CRC cells. INTS3 loss delayed CRC cells growth in vivo. Furthermore, delivery of DOTAP/cholesterol-mshINTS3 nanoparticles inhibited CRC tumor growth. Collectively, our work highlights the role of INTS3 in supporting CRC survival and provides several novel therapeutic targets for treatment.

Rodenticide poisoning leading to cerebral hemorrhage: A case report.

RATIONALE: Anticoagulant rodenticides (ARs) are a substantial fraction of murine types. AR poisoning causes bleeding from the skin, mucous membranes, and multiple organs. However, reports of AR-induced cerebral hemorrhage are scarce. PATIENT CONCERNS: A 40-year-old male presented with dizziness, headache, and limb weakness for 5 days and with coagulopathy. Two days prior to the onset of these symptoms, the patient was exposed to dead mice. DIAGNOSES: Rodenticide intoxication-induced cerebral hemorrhage. INTERVENTIONS: Vitamin K1 infusion, administration of dehydrating agents to reduce intracranial pressure, and correction of acid-base and electrolyte imbalances. OUTCOMES: After 9 days of treatment, the patient's symptoms were relieved, and reexamination revealed that coagulation parameters returned to normal levels. The patient was eventually discharged for observation with oral vitamin K1. CONCLUSIONS: Rodenticide poisoning can lead to intracerebral hemorrhage, and treatment with vitamin K1 infusion is effective. LESSON: Rodenticide poisoning-induced cerebral hemorrhage is rarely reported. Because its symptoms are nonspecific, it is easy to miss the diagnosis or misdiagnose. When patients present with direct and indirect symptoms such as dizziness, headache, and limb weakness, rodenticide poisoning should be considered. Coagulation function and head computed tomography or magnetic resonance imaging examination should be performed at the earliest to confirm the diagnosis and provide timely treatment.

Bioinformatic Identification of Signaling Pathways and Hub Genes in Vascular Dementia

Background: Vascular dementia (VaD) is a prevalent neurodegenerative disease characterized by cognitive impairment due to cerebrovascular factors, affecting a significant portion of the aging population and highlighting the critical need to understand specific targets and mechanisms for effective prevention and treatment strategies. We aimed to identify pathways and crucial genes involved in the progression of VaD through bioinformatics analysis and subsequently validate these findings. Methods: We conducted differential expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and Protein-Protein Interaction (PPI) analysis. We utilized pheochromocytoma 12 (PC12) cells to create an in vitro oxygen-glucose deprivation (OGD) model. We investigated the impact of overexpression and interference of adrenoceptor alpha 1D (ADRA1D) on OGD PC12 cells using TdT-mediated dUTP nick-end labeling (TUNEL), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot (WB), and Fluo-3-pentaacetoxymethyl ester (Fluo-3 AM) analysis. Results: We found 187 differentially expressed genes (DEGs) in the red module that were strongly associated with VaD and were primarily enriched in vasoconstriction, G protein-coupled amine receptor activity, and neuroactive ligand-receptor interaction, mitogen-activated protein kinase (MAPK) signaling pathway, and cell adhesion. Among these pathways, we identified ADRA1D as a gene shared by vasoconstriction, G protein-coupled amine receptor activity, and neuroactive ligand-receptor interaction. The TUNEL assay revealed a significant decrease in PC12 cell apoptosis with ADRA1D overexpression (p < 0.01) and a significant increase in apoptosis upon silencing ADRA1D (p < 0.01). RT-qPCR and WB analysis revealed elevated ADRA1D expression (p < 0.001) ... (AU)

Spatial analysis of the influence on "microplastic communities" in the water at a medium scale.

The issue of microplastics in freshwater has been growing in concern. Besides their abundance, the characteristics of microplastics are also important issues. The concept of "microplastic communities" has been utilized to assess differences in microplastic characteristics. In this study, we utilized the "microplastic community" approach to evaluate the impact of land use on microplastic characteristics in water at a provincial scale in China. The abundance of microplastics in water bodies in Hubei Province varied between 0.33 items/L and 5.40 items/L, with an average of 1.74 items/L. Microplastics were significantly more abundant in rivers than in lakes and reservoirs, and their abundance was negatively correlated with the distance from the nearest residential district of sampling sites. Similarities of microplastic communities were significantly different in mountainous and plain areas. Anthropogenic surfaces increased microplastic abundance and tended to decrease the size of microplastics, whereas natural vegetation had the opposite effect. The effect of land use on microplastic community similarity was greater than that of geographic distance. However, spatial scale limits the effect of various factors on microplastic community similarity. This study revealed the comprehensive influence of land use on microplastic characteristics in water and emphasized the importance of spatial scale in the study of microplastic characteristics.

mcPGK1-dependent mitochondrial import of PGK1 promotes metabolic reprogramming and self-renewal of liver TICs.

Liver tumour-initiating cells (TICs) contribute to tumour initiation, metastasis, progression and drug resistance. Metabolic reprogramming is a cancer hallmark and plays vital roles in liver tumorigenesis. However, the role of metabolic reprogramming in TICs remains poorly explored. Here, we identify a mitochondria-encoded circular RNA, termed mcPGK1 (mitochondrial circRNA for translocating phosphoglycerate kinase 1), which is highly expressed in liver TICs. mcPGK1 knockdown impairs liver TIC self-renewal, whereas its overexpression drives liver TIC self-renewal. Mechanistically, mcPGK1 regulates metabolic reprogramming by inhibiting mitochondrial oxidative phosphorylation (OXPHOS) and promoting glycolysis. This alters the intracellular levels of α-ketoglutarate and lactate, which are modulators in Wnt/ß-catenin activation and liver TIC self-renewal. In addition, mcPGK1 promotes PGK1 mitochondrial import via TOM40 interactions, reprogramming metabolism from oxidative phosphorylation to glycolysis through PGK1-PDK1-PDH axis. Our work suggests that mitochondria-encoded circRNAs represent an additional regulatory layer controlling mitochondrial function, metabolic reprogramming and liver TIC self-renewal.

PRC1 and RACGAP1 are Diagnostic Biomarkers of Early HCC and PRC1 Drives Self-Renewal of Liver Cancer Stem Cells.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths across the world. Due to the lack of reliable markers for early HCC detection, most HCC patients are diagnosed in middle/late stages. Liver cancer stem cells (CSCs), which are drivers of liver tumorigenesis, usually emerge in the early HCC stage and are also termed as liver tumor initiation cells (TIC). Liver CSCs contribute to initiation, propagation, and metastasis of HCC and also play a key role in tumor therapy. Taking advantage of online-available data sets, bioinformatic analyses, and experimental confirmation, here we have screened out PRC1 and RACGAP1 as reliable markers for early HCC detection. PRC1 or RACGAP1 knockdown dramatically inhibited the proliferation, migration, and invasion capacities of HCC cells, conferring PRC1 and RACGAP1 as predominant modulators for HCC propagation and metastasis. Moreover, the sphere formation capacity of HCC cells was impaired after PRC1 knockdown, revealing the function of PRC1 as a modulator for liver CSC self-renewal. Furthermore, the inhibitor of PRC1 had same phenotypes as PRC1 knockdown in HCC cells. Altogether, PRC1 and RACGAP1 are identified both as prognosis markers for early HCC detection and therapeutic targets for liver cancer and liver CSCs, adding additional layers for the early prognosis and therapy of HCC.

Screening and predicted value of potential biomarkers for breast cancer using bioinformatics analysis.

Breast cancer is the most common cancer and the leading cause of cancer-related deaths in women. Increasing molecular targets have been discovered for breast cancer prognosis and therapy. However, there is still an urgent need to identify new biomarkers. Therefore, we evaluated biomarkers that may aid the diagnosis and treatment of breast cancer. We searched three mRNA microarray datasets (GSE134359, GSE31448 and GSE42568) and identified differentially expressed genes (DEGs) by comparing tumor and non-tumor tissues using GEO2R. Functional and pathway enrichment analyses of the DEGs were performed using the DAVID database. The protein-protein interaction (PPI) network was plotted with STRING and visualized using Cytoscape. Module analysis of the PPI network was done using MCODE. The associations between the identified genes and overall survival (OS) were analyzed using an online Kaplan-Meier tool. The redundancy analysis was conducted by DepMap. Finally, we verified the screened HUB gene at the protein level. A total of 268 DEGs were identified, which were mostly enriched in cell division, cell proliferation, and signal transduction. The PPI network comprised 236 nodes and 2132 edges. Two significant modules were identified in the PPI network. Elevated expression of the genes Discs large-associated protein 5 (DLGAP5), aurora kinase A (AURKA), ubiquitin-conjugating enzyme E2 C (UBE2C), ribonucleotide reductase regulatory subunit M2(RRM2), kinesin family member 23(KIF23), kinesin family member 11(KIF11), non-structural maintenance of chromosome condensin 1 complex subunit G (NCAPG), ZW10 interactor (ZWINT), and denticleless E3 ubiquitin protein ligase homolog(DTL) are associated with poor OS of breast cancer patients. The enriched functions and pathways included cell cycle, oocyte meiosis and the p53 signaling pathway. The DEGs in breast cancer have the potential to become useful targets for the diagnosis and treatment of breast cancer.

AKH-FOXO pathway regulates starvation-induced sleep loss through remodeling of the small ventral lateral neuron dorsal projections.

Starvation caused by adverse feeding stresses or food shortages has been reported to result in sleep loss in animals. However, how the starvation signal interacts with the central nervous system is still unknown. Here, the adipokinetic hormone (AKH)-Fork head Box-O (FOXO) pathway is shown to respond to energy change and adjust the sleep of Drosophila through remodeling of the s-LNv (small ventral lateral neurons) dorsal projections. Our results show that starvation prevents flies from going to sleep after the first light-dark transition. The LNvs are required for starvation-induced sleep loss through extension of the pigment dispersing factor (PDF)-containing s-LNv dorsal projections. Further studies reveal that loss of AKH or AKHR (akh receptor) function blocks starvation-induced extension of s-LNv dorsal projections and rescues sleep suppression during food deprivation. FOXO, which has been reported to regulate synapse plasticity of neurons, acts as starvation response factor downstream of AKH, and down regulation of FOXO level considerably alleviates the influence of starvation on s-LNv dorsal projections and sleep. Taking together, our results outline the transduction pathways between starvation signal and sleep, and reveal a novel functional site for sleep regulation.

Greater Performance of Exotic Elodea nuttallii in Response to Water Level May Make It a Better Invader Than Exotic Egeria densa During Winter and Spring.

The strategy of producing rapid initial growth and establishing early in the growing season is important, and it is employed by invasive macrophytes. Elodea nuttallii and Egeria densa, two Hydrocharitaceae species, became weeds after invading many countries in recent years. Comparative studies on their invasive traits in relation to native species during winter and spring are limited. In the present study, we compared the growth performance of these two exotic species with a perennial native species, Potamogeton maackianus, in different water depths (1, 2, and 3 m) during winter (January and February) and spring (March and April). Three morphological traits (shoot number, root number and shoot length), total biomass, relative growth rate (RGR) and two physiological photosynthetic traits (total chlorophyll content and the maximum quantum yield of PSII [Fv/Fm]) were measured for each macrophyte. All three species could overwinter as entirely leafy plants. Biomass, RGR, morphological traits and physiological traits were all different among species. However, water depths had a significant effect only on morphological traits. At all water depths, E. nuttallii had significantly higher values for morphological traits, total biomass and RGR than P. maackianus, while E. densa had significantly fewer roots and a lower total chlorophyll content than P. maackianus. Except for Fv/Fm at a 3 m water depth, morphological and physiological photosynthetic traits, biomass and RGR of E. nuttallii were significantly higher than those of E. densa. In addition, a large number of adventitious roots developed from E. nuttallii but not from the other two species. These results indicate that the advantages of E. nuttallii to grow in winter and spring may make it more prone to expansion than E. densa in China.

Effects of Water Quality Adjusted by Submerged Macrophytes on the Richness of the Epiphytic Algal Community.

Submerged macrophytes and epiphytic algae play significant roles in the functioning of aquatic ecosystems. Submerged macrophytes can influence the epiphytic algal community by directly or indirectly modifying environmental conditions (nutrients, light, etc.). From December to June of the following year, we investigated the dynamics of the dominant winter species Potamogeton crispus, its epiphytic algae, and water quality parameters in the shallow Liangzi Lake in China. The richness of epiphytic algae had a trend similar to that of P. crispus coverage, which increased in the first four months and then decreased in the following three months. The structural equation model (SEM) showed that P. crispus affected the richness of epiphytic algae by reducing nutrient concentrations (reduction in total organic carbon, total nitrogen and chemical oxygen demand) and enhancing water transparency (reduction in turbidity and total suspend solids) to enhance the richness of epiphytic algae. The results indicated that high amounts of submerged macrophyte cover can increase the richness of the epiphytic algal community by changing water quality.

Circadian Rhythm Neuropeptides in Drosophila: Signals for Normal Circadian Function and Circadian Neurodegenerative Disease.

Circadian rhythm is a ubiquitous phenomenon in many organisms ranging from prokaryotes to eukaryotes. During more than four decades, the intrinsic and exogenous regulations of circadian rhythm have been studied. This review summarizes the core endogenous oscillation in Drosophila and then focuses on the neuropeptides, neurotransmitters and hormones that mediate its outputs and integration in Drosophila and the links between several of these (pigment dispersing factor (PDF) and insulin-like peptides) and neurodegenerative disease. These signaling molecules convey important network connectivity and signaling information for normal circadian function, but PDF and insulin-like peptides can also convey signals that lead to apoptosis, enhanced neurodegeneration and cognitive decline in flies carrying circadian mutations or in a senescent state.

SUPPRESSING A PEROXIDASE GENE REDUCES SURVIVAL IN THE WHEAT APHID Sitobion avenae.

Peroxidases (POXs) make up a large superfamily of enzymes that act in a wide range of biological mechanisms, including maintaining appropriate redox balances within cells, among other actions. In this study, we cloned a sequence that encodes a POX protein, SaPOX, from wheat aphids, Sitobion avenae. Amino acid sequence alignment showed the SaPOX sequence was conserved with POXs from other insect species. SaPOX mRNA accumulations were present in all nymphal and adult stages, at higher levels during the first and second instar, and lower during later stages in the life cycle. Ingestion of dsRNA specific to POX led to reduced SaPOX mRNA accumulation. Sitobion avenae nymphs continuously exposed to dietary dsPOX via an artificial diet led to reduced survival rate and ecdysis index. We infer that POX is important to maintain the growth and development of S. avenae.