Development of a business model reflecting the impact of the fourth industrial revolution: The case of the Chinese pharmaceutical companies

This dissertation aims to systematically summarize the efforts and attempts of ten leading Chinese companies in order to propose a Canvas Business Model that can be applied as a reference for change in all the Chinese pharmaceutical companies that are conservative about Industry 4.0. The three research questions that were introduced provided guidance to the literature review and to the development of a final canvas business model that fully satisfies the initial research curiosities. This summary model was based on ten intermediate Canvas ones developed from the secondary data concerning the change processes of ten leading Chinese pharmaceutical companies. The most important findings of this research are, as follows: i) identification of the eight technologies more used within an Industry 4.0 approach; ii) specification of the structural change to be engaged by the Chinese pharmaceutical companies addressing a digital technology push; and, iii) description of the expected advantages for Chinese pharmaceutical firms from the related transformation process. In summary, the literature confirms the interest in the empirical canvas model developed in this thesis by supporting it. Finally, the research outcomes should be further studied despite already being relevant to both researchers and practitioners. In fact, Chinese pharmaceutical companies can establish their own transformation strategies according to their status quo by referring to this business model.Esta dissertação visa resumir sistematicamente os esforços e tentativas de dez empresas chinesas líderes a fim de propôr um Modelo de Negócio do tipo CANVAS que possa ser aplicado como referência de mudança em todas as empresas farmacêuticas chinesas que são conservadoras sobre a Indústria 4.0. As três questões de investigação que foram introduzidas orientaram a revisão da literatura e o desenvolvimento de um modelo final de negócio do tipo CANVAS que satisfaça plenamente as curiosidades iniciais de investigação. Este modelo resumo foi baseado em dez modelos intermédios desenvolvidas a partir dos dados secundários relativos aos processos de mudança de dez empresas farmacêuticas chinesas líder. As conclusões mais importantes desta investigação são: i) identificação das oito tecnologias mais utilizadas numa abordagem I4.0; ii) especificação da mudança estrutural a ser empreendida pelas empresas farmacêuticas chinesas, endereçando um impulso tecnológico digital; e, iii) descrição das vantagens esperadas para as empresas farmacêuticas chinesas envolvidas num processo de transformação deste tipo. Em resumo, a literatura confirma o interesse no modelo emírico de negócio do tipo CANVAS desenvolvido nesta tese, apoiando-o. Finalmente, os resultados da investigação devem ser posteriormente investigados, apesar de já serem relevantes tanto para investigadores como para profissionais. De facto, as empresas farmacêuticas chinesas podem estabelecer as suas próprias estratégias de transformação de acordo com o seu status quo e tendo como referência o modelo de negócio desenvolvido e apresentado nesta dissertação

Case report: A rare case of desmoid-type fibromatosis originating in the small intestine

BackgroundDesmoid-type fibromatosis (DF) is characterized by a rare monoclonal fibroblast proliferation that exhibits variable and unpredictable clinical presentation. DF can be classified into sporadic and hereditary types. Despite extensive research efforts, the exact etiology of DF remains elusive.Case descriptionA 31-year-old male patient presented to the hospital with a progressively growing mass in the right lower abdomen, accompanied by abdominal discomfort. Symptoms are discovered 1 week before admission. Enteroscopy revealed no evidence of colonic abnormalities, and blood tests did not indicate any abnormalities. Due to the indeterminate nature of the mass during surgery, a partial resection of the ileum and cecum was performed, followed by ileocolonic end-to-end anastomosis, with no postoperative complications. The final pathological diagnosis confirmed primary desmoid-type fibromatosis of the distal ileum (invasive fibromatosis). To effectively manage DF, we recommend a follow-up schedule for patients. This includes appointments every 3 months in the first year following surgery, followed by appointments every 6 months up to the fifth year, and then once a year thereafter. The follow-up examinations should include collection of the patient’s medical history, physical examination, blood tests, ultrasounds, CT scans, and other relevant assessments. During the first year of the follow-up period, no further treatment was administered, and the patient remained disease-free.ConclusionDesmoid-type fibromatosis (DF) originating from the small intestine is an extremely rare condition that exhibits local invasiveness and can be life-threatening. Despite its benign histology, DF has a high local recurrence rate and lacks metastatic potential. Diagnosis of DF remains challenging, especially in cases where surgical intervention is not feasible due to asymptomatic patients or partial organ impairment. In such cases, a “watchful waiting” approach is recommended as the initial treatment strategy. However, when preoperative diagnosis is difficult, surgery is typically considered the best option. Given the potential for local recurrence and the uncertain long-term prognosis, regular follow-up is necessary

Enhanced plastic deformation ability of copper matrix composites through synergistic strengthening of nano-Al2O3 and Cr particles

The commercial application of Al2O3/Cu composites (ODS copper) with high Al2O3 content is consistently restricted by their plastic deformability. In order to synergistically improve the plastic deformability of Al2O3/Cu composites, Al2O3/Cu–Cr composites with different Cr contents are prepared by internal oxidation combined with heat treatment by replacing part of the Al2O3 particles with Cr phases heat treatment. The effects of Cr content on the microstructure and plastic deformability of Al2O3/Cu–Cr composites are investigated. It is found that the nano-Al2O3 (8 nm) and Cr (25 nm) particles are uniformly distributed in the copper matrix, and both reach a semi-congruent interface with copper matrix. Meanwhile, the copper matrix undergoes a transition from a [111]Cu hard orientation to a [100]Cu soft orientation, and the increase in Cr content leads to a more pronounced degree of recrystallization in the Al2O3/Cu–Cr composites. The results of geometric phase analysis (GPA) show that the coordinated deformability between Cr and Cu is better than that between Al2O3 and Cu. The elongation of 2.5Al2O3/Cu-0.3Cr composite increased to 24.48 % from 22.47 % of the Cr-free 2.8Al2O3/Cu composite. The results of tensile strength calculations show that the tensile strength of Al2O3/Cu–Cr composites is mainly dominated by matrix strengthening and Orowan strengthening induced by Al2O3 particles, while grain strengthening, dislocation strengthening, and Orowan strengthening induced by Cr particles play a secondary role. The correlation coefficient (R2) is 0.95 after fitting the experimental and theoretical values of tensile strength of Al2O3/Cu–Cr composites

Dietary Lysozyme Alters Sow’s Gut Microbiota, Serum Immunity and Milk Metabolite Profile

The aim of current study was to determine variations in sow’s gut microbiota, serum immunity, and milk metabolite profile mediated by lysozyme supplementation. Twenty-four pregnant sows were assigned to a control group without supplementation and two treatments with 0.5 kg/t and 1.0 kg/t lysozyme provided in formula feed for 21 days (n = 8 per treatment). Microbiota analysis and metagenomic predictions were based on 16s RNA high-throughput sequencing. Milk metabolome was assessed by untargeted liquid chromatography tandem mass spectrometry. Serum biochemical indicators and immunoglobulins were also determined. Gut microbial diversity of sows receiving 1.0 kg/t lysozyme treatment was significantly reduced after the trial. Spirochaetes, Euryarchaeota, and Actinobacteria significantly increased while Firmicutes showed a remarkable reduction in 1.0 kg/t group compared with control. Lysozyme addition rebuilt sow’s gut microbiota to beneficial composition identified by reduced richness of Escherichia coli and increased abundance of Lactobacillus amylovorus. Accordingly, microbial metabolic functions including pyrimidine metabolism, purine metabolism, and amino acid related enzymes were significantly up-regulated in 1.0 kg/t group. Microbial metabolic phenotypes like the richness of Gram-positive bacteria and oxidative stress tolerance were also significantly reduced by lysozyme treatment. Serum alanine transaminase (ALT) activity and IgA levels were significantly down-regulated in the 1.0 kg/t group compared with control, but IgM levels showed a significantly increase in 1.0 kg/t group. Milk metabolites such as L-glutamine, creatine, and L-arginine showed significantly dose-dependent changes after treatment. Overall, lysozyme supplementation could effectively improve the composition, metabolic functions, and phenotypes of sow’s gut microbiota and it also benefit sows with better serum immunity and milk composition. This research could provide theoretical support for further application of lysozyme in promoting animal gut health and prevent pathogenic infections in livestock production

Enhanced high-temperature mechanical properties of the Cu–1.16Ni–0.36Cr alloy owing to interactions between metastable precipitates and dislocations

Herein, an alloy Cu–1.16Ni–0.36Cr with outstanding high-temperature mechanical properties was obtained, and the underlying mechanism was discussed. The properties were compared with those of commercial Cu–Fe–P alloys. The alloy exhibited a high-temperature softening temperature of 674.7 °C. Tensile tests conducted at high temperatures revealed that at 700 °C, the alloy maintained a tensile strength of 131.3 MPa, whereas Cu–Fe–P alloys only exhibited a tensile strength of 58.7 MPa. Microstructural analysis revealed the formation of nanoscale Ni3Cr7 precipitates near fractures at high temperatures, with the average size being approximately 10 nm. These nanoscale precipitates hindered the coarsening of Cr particles and dislocation slips, forming dislocation rings and substantially enhancing the high-temperature mechanical properties of the alloy. Furthermore, the nanoscale precipitates considerably impeded the growth and expansion of recrystallized grains. After a high-temperature treatment at 700 °C, a portion of the microstructure in the alloy remained stretched, with the small-angle grain boundaries being high (68.2%) and the recrystallization degree being only 50.4%

PPARγ/mTOR Regulates the Synthesis and Release of Prostaglandins in Ovine Trophoblast Cells in Early Pregnancy

Trophoblast cells synthesize and secrete prostaglandins (PGs), which are essential for ruminants in early gestation to recognize pregnancy. Hormones in the intrauterine environment play an important role in regulating PGs synthesis during implantation, but the underlying mechanism remains unclear. In this study, co-treatment of sheep trophoblast cells (STCs) with progesterone (P4), estradiol (E2), and interferon-tau (IFN-τ) increased the ratio of prostaglandin E2 (PGE2) to prostaglandin F2α (PGF2α) and upregulated peroxisome proliferator-activated receptor γ (PPARγ) expression, while inhibiting the mechanistic target of rapamycin (mTOR) pathway and activating cellular autophagy. Under hormone treatment, inhibition of PPARγ activity decreased the ratio of PGE2/PGF2α and cellular activity, while activating expression of the mTOR downstream marker—the phosphorylation of p70S6K (p-p70S6K). We also found that the PPARγ/mTOR pathway played an important role in regulating trophoblast cell function. Inhibition of the mTOR pathway by rapamycin increased the ratio of PGE2/PGF2α and decreased the expression of apoptosis-related proteins after inhibiting PPARγ activity. In conclusion, our findings provide new insights into the molecular mechanism of prostaglandin regulation of trophoblast cells in sheep during early pregnancy, indicating that the PPARγ/mTOR pathway plays an important role in PGs secretion and cell viability

Anti-Eavesdropping by Exploiting the Space–Time Coupling in UANs

Due to the space–time coupling access, we find that anti-eavesdropping opportunities exist in underwater acoustic networks (UANs), where packets can be successfully received only by the intended receiver, but collide at the unintended receivers. These opportunities are highly spatially dependent, and this paper studies the case that linearly deployed sensor nodes directly report data toward a single collector. We found an eavesdropping ring centered around these linearly deployed sensor nodes, where the eavesdropper could steal all the reported data. Since the typical receiving-alignment-based scheduling MAC (TRAS-MAC) will expose the relative spatial information among the sensor nodes with the collector, the eavesdropper can locate the eavesdropping ring. Although moving the collector into the one-dimensional sensor node chain can degrade the eavesdropping ring to a point that constrains the eavesdropping risk, the collector’s location will be subsequently exposed to the eavesdropper. To efficiently protect the reported data and prevent the exposure of the collector’s location, we designed a slotted- and receiving-alignment-based scheduling MAC (SRAS-MAC). The NS-3 simulation results showed the effectiveness of the SRAS-MAC and the TRAS-MAC in protecting data from eavesdropping, which protect 90% of the data from eavesdropping in the one-eavesdropper case and up to 80% of data from eavesdropping in ten-eavesdropper cases. Moreover, unlike TRAS-MAC, which will expose the collector’s location, SRAS-MAC provides multiple positions for the collector to hide, and the eavesdropper cannot distinguish where it is

The Impact of Air Pollution on Intestinal Microbiome of Asthmatic Children: A Panel Study

Air pollution could impact on the alteration of intestinal microbiome. Maturation of intestinal microbiome in early life played an important role in the development of allergic diseases, including asthma. Recent studies presented an increase in the evidence of association between the shift of gut microbiota and asthma. This article is aimed at exploring whether the alteration in the intestinal microbiome triggered by a short wave of air pollution could influence the colonization of bacteria that have been related to the immunological mechanisms of the asthma attack. The impact of air pollution on intestinal microbiome was assessed by longitudinal comparison. Fecal samples were collected twice for twenty-one children in clean and smog days, respectively, including eleven asthmatic children and ten healthy children. Intestinal bacteria were discriminated by using the method of 16S rRNA gene sequence. The results showed that the composition of intestinal microbiome changed between clean and smog days among all children (PERMANOVA, P=0.03). During smog days, Bifidobacteriaceae, Erysipelotrichaceae, and Clostridium sensu stricto 1 decreased, and Streptococcaceae, Porphyromonadaceae, Rikenellaceae, Bacteroidales S24-7 group, and Bacteroides increased in asthmatic children (Wilcoxon test, P<0.05), while Fusicatenibacter decreased and Rikenellaceae and Terrisporobacter increased in healthy children (Wilcoxon test, P<0.05). After controlling for food consumption, the relative abundance of some bacteria belonging to Firmicutes negatively associated with concentration of PM2.5, PM10, NO2, and SO2 (multiple linear regression, P<0.05). This study demonstrated that short wave of air pollution had an impact on the intestinal microbiome of asthmatic children. Intestinal bacteria, which have been related to immunological mechanisms of asthma attack, were also found to be associated with air pollution. This finding suggested that a short wave of air pollution may trigger asthma by impacting on intestinal bacteria

Effect of Calefaction and Stress Relaxation on Grain Boundaries/Textures of Cu–Cr–Ni Alloy

The Cu–Cr–Ni alloy is a key material for the manufacturing of connectors, which requires excellent resistance to stress relaxation. However, the inherent correlation among microstructure, texture, and properties is still unclear. In this study, we investigated the influence of calefaction and stress relaxation on the grain boundaries (GBs), textures, and properties of the Cu–Cr–Ni alloy. The results showed that calefaction and stress relaxation had opposite effects on GBs and textures. Calefaction led to a decrease in the proportion of low-angle grain boundaries (LAGBs), an increase in the Schmidt factor (SF) value of the grains, and a transition of texture from to . The grains with higher SF values were more susceptible to plastic deformation, which deteriorated the stress relaxation resistance. By comparison, stress relaxation led to an increase in the proportion of LAGBs, a decrease in SF values of the grains, and a transition of texture from to and . After stress relaxation, the variation trends of the GBs and textures were consistent with those of other plastic deformations, indicating that stress relaxation can be verified by the variations in GBs and textures. Our findings provide a theoretical basis for improvements in stress relaxation resistance of the Cu-based alloys used in connector industry