Engineered extracellular vesicles carrying let-7a-5p for alleviating inflammation in acute lung injury.

BACKGROUND: Acute lung injury (ALI) is a life-threatening respiratory condition characterized by severe inflammation and lung tissue damage, frequently causing rapid respiratory failure and long-term complications. The microRNA let-7a-5p is involved in the progression of lung injury, inflammation, and fibrosis by regulating immune cell activation and cytokine production. This study aims to use an innovative cellular electroporation platform to generate extracellular vesicles (EVs) carring let-7a-5p (EV-let-7a-5p) derived from transfected Wharton's jelly-mesenchymal stem cells (WJ-MSCs) as a potential gene therapy for ALI. METHODS: A cellular nanoporation (CNP) method was used to induce the production and release of EV-let-7a-5p from WJ-MSCs transfected with the relevant plasmid DNA. EV-let-7a-5p in the conditioned medium were isolated using a tangential flow filtration (TFF) system. EV characterization followed the minimal consensus guidelines outlined by the International Society for Extracellular Vesicles. We conducted a thorough set of therapeutic assessments, including the antifibrotic effects using a transforming growth factor beta (TGF-ß)-induced cell model, the modulation effects on macrophage polarization, and the influence of EV-let-7a-5p in a rat model of hyperoxia-induced ALI. RESULTS: The CNP platform significantly increased EV secretion from transfected WJ-MSCs, and the encapsulated let-7a-5p in engineered EVs was markedly higher than that in untreated WJ-MSCs. These EV-let-7a-5p did not influence cell proliferation and effectively mitigated the TGF-ß-induced fibrotic phenotype by downregulating SMAD2/3 phosphorylation in LL29 cells. Furthermore, EV-let-7a-5p regulated M2-like macrophage activation in an inflammatory microenvironment and significantly induced interleukin (IL)-10 secretion, demonstrating their modulatory effect on inflammation. Administering EVs from untreated WJ-MSCs slightly improved lung function and increased let-7a-5p expression in plasma in the hyperoxia-induced ALI rat model. In comparison, EV-let-7a-5p significantly reduced macrophage infiltration and collagen deposition while increasing IL-10 expression, causing a substantial improvement in lung function. CONCLUSION: This study reveals that the use of the CNP platform to stimulate and transfect WJ-MSCs could generate an abundance of let-7a-5p-enriched EVs, which underscores the therapeutic potential in countering inflammatory responses, fibrotic activation, and hyperoxia-induced lung injury. These results provide potential avenues for developing innovative therapeutic approaches for more effective interventions in ALI.

Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis.

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

Study on the Consistency Between Automatic Measurement Based on Convolutional Neural Network Technology and Manual Visual Evaluation in Intracavitary Ultrasonic Cine of Anterior Pelvic.

OBJECTIVES: This study was to evaluate the application of automatic measurement based on convolutional neural network (CNN) technology in intracavitary ultrasound cine of anterior pelvic. METHODS: A total of 500 patients who underwent pelvic floor ultrasound examination at Peking University Shenzhen Hospital from July 2021 to February 2022 were retrospectively retrieved by the picture archiving and communication system (PACS) system, and 300 cases were used as a training set. The training set was labeled by three experienced ultrasound physicians to train CNN models and develop an automatic measurement software. The remaining 200 cases were used as a test set. Automatic measurement software identified relevant anatomical structures frame by frame and determined the two frames with the greatest difference, calculated the bladder neck descent (BND), urethral rotation angle (URA), and retrovesical angle (RA). Meanwhile, two experienced ultrasound physicians evaluated the resting frame and the maximum Valsalva frame on the cines by manual visual evaluation, labeled the anatomical structures in the corresponding frame, such as the inferoposterior margin of pubic symphysis, the mid-axis of pubic symphysis, bladder contour, and urethra in the front, and calculated BND, URA, and RA. Considering that the residual urine volume (RUV) in the bladder may affect the results, enrolled patients were grouped according to the RUV (10-50 mL, 50-100 mL, and >100 mL). The consistency of the results by automatic measurement and manual visual evaluation was evaluated using the intraclass correlation coefficient (ICC) and the Bland-Altman graph. RESULTS: Of the 200 cases in the test set, 120 cases were successfully identified by the CNN automatic software with a 60% recognition rate. In the case of successful identification, the ICC of manual visual evaluation measurement and automatic measurement was 0.936 (BND), 0.911 (URA), 0.756 (RA in rest), and 0.877 (RA at maximum Valsalva), respectively. In addition, the RUV had a negligible effect on the consistency. The Bland-Altman plot shows the proportion of samples outside the limit was below 5%. CONCLUSIONS: CNN-based automatic measurement software exhibited high reliability in anterior pelvic measurement, which results in a significantly enhanced measurement efficiency.

Comparative Study on Anti-Inflammatory Effect of Polysaccharides from Vinegar-Baked Radix Bupleuri Using Different Methods.

The impact of the extraction method on the physiochemical characteristics and anti-inflammatory effect of polysaccharides from vinegar-baked Radix Bupleuri (VBCPs) was studied. Five extraction methods were employed to obtain the VBCPs: hot water extraction (HW), ultrasound-assisted extraction (UA), enzyme-assisted extraction (EA), citric acid-assisted extraction (CA), and ammonia-assisted extraction (KA). The results showed that the extraction method affects the yield, characteristics, and anti-inflammatory effect of the polysaccharides significantly. KA produced the highest yield, Ara content, and the strongest effect of enhancing IL-10 secretion. VBCP-EA exhibited the largest molecular weight (Mw), the highest Man content, and the poorest effect on inhibiting NO, VBCP-UA possessed more Gal than other VBCPs, the lowest Mw, and a comparable effect on inhibiting NO and TNF-α with VBCP-KA and VBCP-CA. All VBCP self-assembled into nanoparticles in solutions, and VBCP-KA presented the lowest particle size. The structure-activity analysis showed that Mw and Man content are negatively correlated and Ara content is positively correlated with the NO inhibition and IL-10 secretion effects; Rha and Gal A content are positively correlated and Glu is negatively correlated with the TNF-α inhibiting effect. The above results indicated that KA is an efficient method for obtaining anti-inflammatory VBCP, which provides new insight into the extraction of VBCP.

An Oral Microbial Biomarker for Early Detection of Recurrence of Oral Squamous Cell Carcinoma.

Changes in the oral microbiome are associated with oral squamous cell carcinoma (OSCC). Oral microbe-derived signatures have been utilized as markers of OSCC. However, the structure of the oral microbiome during OSCC recurrence and biomarkers for the prediction of OSCC recurrence remains unknown. To identify OSCC recurrence-associated microbial biomarkers for the prediction of OSCC recurrence, we performed 16S rRNA amplicon sequencing on 54 oral swab samples from OSCC patients. Differences in bacterial compositions were observed in patients with vs without recurrence. We found that Granulicatella, Peptostreptococcus, Campylobacter, Porphyromonas, Oribacterium, Actinomyces, Corynebacterium, Capnocytophaga, and Dialister were enriched in OSCC recurrence. Functional analysis of the oral microbiome showed altered functions associated with OSCC recurrence compared with nonrecurrence. A random forest prediction model was constructed with five microbial signatures including Leptotrichia trevisanii, Capnocytophaga sputigena, Capnocytophaga, Cardiobacterium, and Olsenella to discriminate OSCC recurrence from original OSCC (accuracy = 0.963). Moreover, we validated the prediction model in another independent cohort (46 OSCC patients), achieving an accuracy of 0.761. We compared the accuracy of the prediction of OSCC recurrence between the five microbial signatures and two clinicopathological parameters, including resection margin and lymph node counts. The results predicted by the model with five microbial signatures showed a higher accuracy than those based on the clinical outcomes from the two clinicopathological parameters. This study demonstrated the validity of using recurrence-related microbial biomarkers, a noninvasive and effective method for the prediction of OSCC recurrence. Our findings may contribute to the prognosis and treatment of OSCC recurrence.

The subgenome Saccharum spontaneum contributes to sugar accumulation in sugarcane as revealed by full-length transcriptomic analysis.

INTRODUCTION: Modern sugarcane cultivars (Saccharum spp. hybrids) derived from crosses between S. officinarum and S. spontaneum, with high-sugar traits and excellent stress tolerance inherited respectively. However, the contribution of the S. spontaneum subgenome to sucrose accumulation is still unclear. OBJECTIVE: To compensate for the absence of a high-quality reference genome, a transcriptome analysis method is needed to analyze the molecular basis of differential sucrose accumulation in sugarcane hybrids and to find clues to the contribution of the S. spontaneum subgenome to sucrose accumulation. METHODS: PacBio full-length sequencing was used to complement genome annotation, followed by the identification of differential genes between the high and low sugar groups using differential alternative splicing analysis and differential expression analysis. At the subgenomic level, the factors responsible for differential sucrose accumulation were investigated from the perspective of transcriptional and post-transcriptional regulation. RESULTS: A full-length transcriptome annotated at the subgenomic level was provided, complemented by 263,378 allele-defined transcript isoforms and 139,405 alternative splicing (AS) events. Differential alternative splicing (DA) analysis and differential expression (DE) analysis identified differential genes between high and low sugar groups and explained differential sucrose accumulation factors by the KEGG pathways. In some gene models, different or even opposite expression patterns of alleles from the same gene were observed, reflecting the potential evolution of these alleles toward novel functions in polyploid sugarcane. Among DA and DE genes in the sucrose source-sink complex pathway, we found some alleles encoding sucrose accumulation-related enzymes derived from the S. spontaneum subgenome were differentially expressed or had DA events between the two contrasting sugarcane hybrids. CONCLUSION: Full-length transcriptomes annotated at the subgenomic level could better characterize sugarcane hybrids, and the S. spontaneum subgenome was found to contribute to sucrose accumulation.

Generation of induced pluripotent stem cells from Bornean orangutans.

Introduction: Orangutans, classified under the Pongo genus, are an endangered non-human primate (NHP) species. Derivation of induced pluripotent stem cells (iPSCs) represents a promising avenue for conserving the genetic resources of these animals. Earlier studies focused on deriving orangutan iPSCs (o-iPSCs) from Sumatran orangutans (Pongo abelii). To date, no reports specifically target the other Critically Endangered species in the Pongo genus, the Bornean orangutans (Pongo pygmaeus). Methods: Using Sendai virus-mediated Yamanaka factor-based reprogramming of peripheral blood mononuclear cells to generate iPSCs (bo-iPSCs) from a female captive Bornean orangutan. In this study, we evaluate the colony morphology, pluripotent markers, X chromosome activation status, and transcriptomic profile of the bo-iPSCs to demonstrate the pluripotency of iPSCs from Bornean orangutans. Results: The bo-iPSCs were successfully derived from Bornean orangutans, using Sendai virus-mediated Yamanaka factor-based reprogramming of peripheral blood mononuclear cells. When a modified 4i/L/A (m4i/L/A) culture system was applied to activate the WNT signaling pathway in these bo-iPSCs, the derived cells (m-bo-iPSCs) manifested characteristics akin to human naive pluripotent stem cells, including high expression levels of KLF17, DNMT3L, and DPPA3/5, as well as the X chromosome reactivation. Comparative RNA-seq analysis positioned the m-bo-iPSCs between human naive and formative pluripotent states. Furthermore, the m-bo-iPSCs express differentiation capacity into all three germlines, evidenced by controlled in vitro embryoid body formation assay. Discussion: Our work establishes a novel approach to preserve the genetic diversity of endangered Bornean orangutans while offering insights into primate stem cell pluripotency. In the future, derivation of the primordial germ cell-like cells (PGCLCs) from m-bo-iPSCs is needed to demonstrate the further specific application in species preservation and broaden the knowledge of primordial germ cell specification across species.

Advances in the study of new BCR-ABL kinase inhibitors / 药学学报

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

Effects and mechanism of Elafibranor on the proliferation, migration and apoptosis of human prostate cancer / 现代泌尿外科杂志

【Objective】 To investigate the effects and molecular mechanism of Elafibranor (ELA) on the proliferation, migration and apoptosis of human prostate cancer (PCa) cells. 【Methods】 After PCa DU145 cells were treated with culture media containing different dosages of ELA, the proliferation, migration and apoptosis were determined with MTT assay, wound healing assay and Transwell assay, respectively. The expressions of genes related to lipid metabolism were detected with real-time quantitative polymerase chain reaction (real-time qPCR). 【Results】 The relative cell proliferation rate at 48 h was 100% in the blank control group, (86.9±7.8)% in the low-dose (5 μmol/L) group and (58.5±9.4)% in the high-dose (15 μmol/L) group;the wound healing rate at 24 h was (74.7±3.2)%, (61.8±2.9)% and (53.2±3.3)%;the relative percentage of migrated cells at 24 h was 100%, (32.4±11.2)% and (15.4±3.2)%;the cell apoptosis rate at 48 h was (9.3±1.4)%, (11.3±0.3)%, and (15.2±4.5)%, respectively, all P<0.05. After ELA treatment for 48 h, the genes related to fatty acid intake (SCPX, PLTP) and fatty acid oxidation (PDK1, ACOX2) were significantly down-regulated in the high-dose group, while the gene related to fatty acid deposition (PLIN2) was significantly up-regulated, indicating that the lipid metabolism pathway of DU145 cells was seriously interfered by the ELA treatment. 【Conclusion】 ELA can inhibit the proliferation and migration, and promote the apoptosis of prostate cancer cells by interfering in the lipid metabolism pathway, which exhibits remarkable potential of clinical translation in the field of anti-tumor chemotherapy.

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents / 医学前沿

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents / 医学前沿

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Surfactant-Modified CdS/CdCO3 Composite Photocatalyst Morphology Enhances Visible-Light-Driven Cr(VI) Reduction Performance.

The surfactant modification of catalyst morphology is considered as an effective method to improve photocatalytic performance. In this work, the visible-light-driven composite photocatalyst was obtained by growing CdS nanoparticles in the cubic crystal structure of CdCO3, which, after surfactant modification, led to the formation of CdCO3 elliptical spheres. This reasonable composite-structure-modification design effectively increased the specific surface area, fully exposing the catalytic-activity check point. Cd2+ from CdCO3 can enter the CdS crystal structure to generate lattice distortion and form hole traps, which productively promoted the separation and transfer of CdS photogenerated electron-hole pairs. The prepared 5-CdS/CdCO3@SDS exhibited excellent Cr(VI) photocatalytic activity with a reduction efficiency of 86.9% within 30 min, and the reduction rate was 0.0675 min-1, which was 15.57 and 14.46 times that of CdS and CdCO3, respectively. Finally, the main active substances during the reduction process, the photogenerated charge transfer pathways related to heterojunctions and the catalytic mechanism were proposed and analyzed.

Effectiveness of calamine lotion as an adjunctive therapy to mometasone furoate ointment in the treatment of infant eczema: A retrospective study.

This retrospective study investigated the effectiveness of calamine lotion (CL) as an adjunctive therapy to mometasone furoate ointment (MFO) in the treatment of infant eczema (IE). This retrospective study analyzed the electronic medical records of 50 IE infants. They were allocated to a treatment group or a control group, with 25 subjects in each group. All infants in both groups received MFO. In addition, infants in the treatment group underwent CL. The outcomes were effectiveness based on the eczema area and severity index, lesion area, and pruritus severity. We analyzed the outcomes before and after treatment. The results of this study showed that infants in the treatment group had more effective in effectiveness based on eczema area and severity index (P < .01), lesion area (P < .01), and pruritus severity (P = .01) than those in the control group. However, no medical records reported any adverse events in either group. The results of this study showed that CL added to MFO was more effective than MFO alone in the treatment of infants with IE.

Fluorescent Eu3+/Tb3+ Metal-Organic Frameworks for Ratiometric Temperature Sensing Regulated by Ligand Energy.

This work presents three series of Eu/Tb metal-organic frameworks (MOFs) containing benzophenone-4,4'-dicarboxylic acid (H2BPNDC), 4,4'-dicarboxydiphenyl ether (H2OBA), and terephthalic acid (H2BDC) as the ligands. Eu/Tb MOFs have the same structural features in that their 3D frameworks are simplified as 2,3,10-connected {42.6}2{46.618.819.102}{4}2 topological networks. The solid-state fluorescence spectra of three Eu/Tb MOF series are attributed to the combined emissions of 5D0 → 7FJ (J = 1-4) transitions in Eu3+ and 5D4 → 7FJ (J = 6-5) transitions in Tb3+. The nEu:nTb of Eu/Tb MOFs is optimized as 1:69 based on the relationships between ITb(545)/IEu(614) and nEu:nTb; that is, Eu0.0143Tb0.9857-L (L = BPNDC2-, OBA2-, and BDC2-) were selected to carry out the following temperature (T)-sensing tests. The fluorescence mechanism of Eu0.0143Tb0.9857-L can be explained by a ligand-to-metal charge transfer combined with an intermetallic Tb3+ → Eu3+ energy transfer. The T-dependent fluorescence indicates linear relationships with sensitivities of 1.85% K-1 for Eu0.0143Tb0.9857-BPNDC, 6.49% K-1 for Eu0.0143Tb0.9857-OBA, and 0.28% K-1 for Eu0.0143Tb0.9857-BDC. The influence of T on the lowest excited triplet energy levels (T1 values) of the ligands reveals that the ligand energy regulation impacts their fluorescence properties, including the sensitivity, fluorescence quenching rate, quantum yield, and fluorescence lifetime. This shows that Eu0.0143Tb0.9857-BPNDC is sufficiently sensitive to T, making it applicable in noncontact T measurements.

Comparative Analysis of Chloroplast Genome in Saccharum spp. and Related Members of 'Saccharum Complex'.

High ploids of the sugarcane nuclear genome limit its genomic studies, whereas its chloroplast genome is small and conserved, which is suitable for phylogenetic studies and molecular marker development. Here, we applied whole genome sequencing technology to sequence and assemble chloroplast genomes of eight species of the 'Saccharum Complex', and elucidated their sequence variations. In total, 19 accessions were sequenced, and 23 chloroplast genomes were assembled, including 6 species of Saccharum (among them, S. robustum, S. sinense, and S. barberi firstly reported in this study) and 2 sugarcane relative species, Tripidium arundinaceum and Narenga porphyrocoma. The plastid phylogenetic signal demonstrated that S. officinarum and S. robustum shared a common ancestor, and that the cytoplasmic origins of S. sinense and S. barberi were much more ancient than the S. offcinarum/S. robustum linage. Overall, 14 markers were developed, including 9 InDel markers for distinguishing Saccharum from its relative species, 4 dCAPS markers for distinguishing S. officinarum from S. robustum, and 1 dCAPS marker for distinguishing S. sinense and S. barberi from other species. The results obtained from our studies will contribute to the understanding of the classification and plastome evolution of Saccharinae, and the molecular markers developed have demonstrated their highly discriminatory power in Saccharum and relative species.

Analysis of Equity Disputes in Listed Companies With Dispersed Ownership Structure and Protection of Small and Medium Shareholders' Interests.

This paper selected Vanke as the case to study the governance problems of Vanke and the protection of the interests of small and medium shareholders under the situation of equity disputes. At the same time, the study further explored the advantages and disadvantages of the dispersed ownership structure, the long-term impact on the company's development and the choice of the involved corporate governance methods under the current Chinese capital market conditions. This paper adopted the event research method and selected the period from June 2015 to June 2017 (24 months) as the observation period to analyze the market performance impact of Vanke in the equity disputes. At the same time, this paper also measured Vanke 's individual stock rate of return (R it ) and market rate of return (R mt ), and calculated Vanke 's normal rate of return [E(R i,t )], abnormal rate of return (AR i,t ), and cumulative abnormal rate of return (CAR i ) during different event windows ([-3,10]). Vanke 's shareholding was too dispersed and the stock price had been sluggish for a long time, which had greatly reduced the acquisition difficulty and cost of Baoneng , thus triggering the "barbarian invasion" of Baoneng . In the struggle for control, whether it was Vanke 's anti-takeover measures or China Resources , Baoneng , and Evergrande 's competition for equity, their actions had harmed the interests of small and medium shareholders. The market supervision department was too lenient to supervise and punish the interests of small and medium shareholders, and opportunism made behaviors that infringe on the interests of others more reckless. However, small and medium shareholders cannot actively participate in the company's management decision-making to safeguard their legitimate rights and interests, which intensifies the violations of all parties in the equity disputes, thus forming a vicious circle. Therefore, the protection of the interests of small and medium shareholders required the joint efforts and consciousness of regulators, small and medium shareholders, and acquirers.

Risk Assessment of Haier Group's Overseas Investment Under International Financial Reporting Standards.

With the development of economic globalization and the policy guidance of International Financial Reporting Standards (IFRS), the overseas investment of Chinese enterprises has been greatly affected. To study the overseas investment risks of Chinese enterprises, this paper applies a risk analysis model to summarize and analyze the results of overseas investment of Haier from 2008 to 2020. This paper defines the risk analysis model as risk identification, risk assessment, and risk response, and studies overseas investment risks including political, economic, cultural, legal, cost, epidemic, and business risks. (1) The existence of various risks is identified in the company's overseas investment projects; (2). The overseas investment risks of Haier are evaluated, through a comprehensive evaluation method combining qualitative and quantitative, financial data, and market response; (3). In view of the deficiencies of the existing risk prevention measures in the overseas investment of enterprises, some reasonable suggestions are purposed. The innovation of this paper are: This paper combines IFRS 9, IFRS 15, and IFRS 16, selects theories, and combines cases to evaluate the risks of overseas investment that are difficult to quantify, and analyzes the risks of overseas investment by Z-value models and market effects. This research method has pertinence and applicability to enterprises investing overseas.

Application of Business Intelligence in Decision Support to Hospital Management: An Example of Outpatient Clinic Schedule Arrangement.

There is a gap between medical resources and patient needs, Managers need to obtain productivity information to optimize resources allocation. The value of this research is that the information provided by the dashboard allows hospital managers problems respond to it quickly. We recommend the research could integrate more data (such as temperature data, national death population data record), so as to be closed to hospital operating cost control and to estimate patients' needs.

WITHDRAWN: LncRNA-PVT1 Inhibition Protects Neuron Injury During Cerebral Ischemia Injury through Targeting the miRNA-187-3p- MyD88 Signaling Pathway

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The Role of Nutrition in Osteoarthritis: A Literature Review.

A literature review to identify nutritional factors and the prevention and management of knee or hip osteoarthritis (OA) suggests that nutritional interventions offer some health benefits in OA through mechanisms such as weight loss, reduced inflammation, and antioxidant capacity. However, because data are limited with mixed results, high-quality evidence, including longitudinal studies and clinical trials, are needed to understand whether nutritional supplementation effectively prevents or manages OA. Therefore, healthcare professionals should consider promoting diets rich in fiber, including whole grains, fruit, vegetables, nuts, seeds, and legumes or dietary patterns such as the Mediterranean diet, to their patients to manage OA.