Study of Comparative Advantages of Chinese and Indian Pharmaceutical Industries under Globalization

The authors explore the background and major factors that have promoted the growth of Pharmaceutical industry in India. Government policy and globalization strategy have played critical roles in positioning India as a pharmaceutical powerhouse. China, facing similar challenges and opportunities in the global economy, could draw valuable lessons from India’s growth story. There are also synergy and strategic fit between the two emerging economy in the pharmaceutical industry. Key words: China; India; Intellectual Property Rights (IPR); Pharmaceutical industry; MN

Drug delivery systems for oral disease applications

There are many restrictions on topical medications for the oral cavity. Various factors affect the topical application of drugs in the oral cavity, an open and complex environment. The complex physical and chemical environment of the oral cavity, such as saliva and food, will influence the effect of free drugs. Therefore, drug delivery systems have served as supporting structures or as carriers loading active ingredients, such as antimicrobial agents and growth factors (GFs), to promote antibacterial properties, tissue regeneration, and engineering for drug diffusion. These drug delivery systems are considered in the prevention and treatment of dental caries, periodontal disease, periapical disease, the delivery of anesthetic drugs, etc. These carrier materials are designed in different ways for clinical application, including nanoparticles, hydrogels, nanofibers, films, and scaffolds. This review aimed to summarize the advantages and disadvantages of different carrier materials. We discuss synthesis methods and their application scope to provide new perspectives for the development and preparation of more favorable and effective local oral drug delivery systems

Phosphorylation-Dependent 14-3-3 Binding to LRRK2 Is Impaired by Common Mutations of Familial Parkinson's Disease

) are the cause of the most common inherited and some sporadic forms of Parkinson's disease (PD). The molecular mechanism underlying the pathogenic role of LRRK2 mutations in PD remains unknown. and in cell culture, suggesting that PKA is a potential upstream kinase that regulates LRRK2 function. Finally, our study indicates that the common PD-related mutations of LRRK2, R1441G, Y1699C and G2019S, decrease homeostatic phosphorylation levels of S935 and impair 14-3-3 binding of LRRK2., and the phosphorylation of specific sites (e.g. S935) determines 14-3-3 binding of LRRK2. We propose that 14-3-3 is an important regulator of LRRK2-mediated cellular functions. Our study suggests that PKA, a cAMP-dependent kinase involved in regulating dopamine physiology, is a potential upstream kinase that phosphorylates LRRK2 at S935. Furthermore, the reduction of phosphorylation/14-3-3 binding of LRRK2 due to the common familial PD-related mutations provides novel insight into the pathogenic mechanism of LRRK2-linked PD

Phosphorylation-Dependent 14-3-3 Binding to LRRK2 Is Impaired by Common Mutations of Familial Parkinson's Disease

Background: Recent studies show that mutations in Leucine Rich Repeat Kinase 2 (LRRK2) are the cause of the most common inherited and some sporadic forms of Parkinson's disease (PD). The molecular mechanism underlying the pathogenic role of LRRK2 mutations in PD remains unknown.Methodology/Principal Findings: Using affinity purification and mass spectrometric analysis, we investigated phosphorylation sites and binding proteins of LRRK2 purified from mouse brain. We identified multiple phosphorylation sites at N-terminus of LRRK2 including S910, S912, S935 and S973. Focusing on the high stoichiometry S935 phosphorylation site, we developed an anti-pS935 specific antibody and showed that LRRK2 is constitutively phosphorylated at S935 in various tissues (including brain) and at different ages in mice. We find that 14-3-3 proteins (especially isoforms γ and η) bind LRRK2 and this binding depends on phosphorylation of S935. The binding of 14-3-3, with little effect on dimer formation of LRRK2, confers protection of the phosphorylation status of S935. Furthermore, we show that protein kinase A (PKA), but not LRRK2 kinase itself, can cause the phosphorylation of LRRK2 at S935 in vitro and in cell culture, suggesting that PKA is a potential upstream kinase that regulates LRRK2 function. Finally, our study indicates that the common PD-related mutations of LRRK2, R1441G, Y1699C and G2019S, decrease homeostatic phosphorylation levels of S935 and impair 14-3-3 binding of LRRK2.Conclusions/Significance: LRRK2 is extensively phosphorylated in vivo, and the phosphorylation of specific sites (e.g. S935) determines 14-3-3 binding of LRRK2. We propose that 14-3-3 is an important regulator of LRRK2-mediated cellular functions. Our study suggests that PKA, a cAMP-dependent kinase involved in regulating dopamine physiology, is a potential upstream kinase that phosphorylates LRRK2 at S935. Furthermore, the reduction of phosphorylation/14-3-3 binding of LRRK2 due to the common familial PD-related mutations provides novel insight into the pathogenic mechanism of LRRK2-linked PD.</p

An intimate collaboration between peroxisomes and lipid bodies

Although peroxisomes oxidize lipids, the metabolism of lipid bodies and peroxisomes is thought to be largely uncoupled from one another. In this study, using oleic acid–cultured Saccharomyces cerevisiae as a model system, we provide evidence that lipid bodies and peroxisomes have a close physiological relationship. Peroxisomes adhere stably to lipid bodies, and they can even extend processes into lipid body cores. Biochemical experiments and proteomic analysis of the purified lipid bodies suggest that these processes are limited to enzymes of fatty acid β oxidation. Peroxisomes that are unable to oxidize fatty acids promote novel structures within lipid bodies (“gnarls”), which may be organized arrays of accumulated free fatty acids. However, gnarls are suppressed, and fatty acids are not accumulated in the absence of peroxisomal membranes. Our results suggest that the extensive physical contact between peroxisomes and lipid bodies promotes the coupling of lipolysis within lipid bodies with peroxisomal fatty acid oxidation

Lipopolysaccharide-induced depression-like model in mice: meta-analysis and systematic evaluation

Depression is a complex and biologically heterogeneous disorder. Recent studies have shown that central nervous system (CNS) inflammation plays a key role in the development of depression. Lipopolysaccharide (LPS)-induced depression-like model in mice is commonly used to studying the mechanisms of inflammation-associated depression and the therapeutic effects of drugs. Numerous LPS-induced depression-like models in mice exist and differ widely in animal characteristics and methodological parameters. Here, we systematically reviewed studies on PubMed from January 2017 to July 2022 and performed cardinal of 170 studies and meta-analyses of 61 studies to support finding suitable animal models for future experimental studies on inflammation-associated depression. Mouse strains, LPS administration, and behavioral outcomes of these models have been assessed. In the meta-analysis, forced swimming test (FST) was used to evaluate the effect size of different mouse strains and LPS doses. The results revealed large effect sizes in ICR and Swiss mice, but less heterogeneity in C57BL/6 mice. For LPS intraperitoneal dose, the difference did not affect behavioral outcomes in C57BL/6 mice. However, in ICR mice, the most significant effect on behavioral outcomes was observed after the injection of 0.5 mg/kg LPS. Our results suggests that mice strains and LPS administration play a key role in the evaluation of behavioral outcomes in such models

Computational Modelling of Tone Perception Based on Direct Processing of f0 Contours

It has been widely assumed that in speech perception it is imperative to first detect a set of distinctive properties or features and then use them to recognize phonetic units like consonants, vowels, and tones. Those features can be auditory cues or articulatory gestures, or a combination of both. There have been no clear demonstrations of how exactly such a two-phase process would work in the perception of continuous speech, however. Here we used computational modelling to explore whether it is possible to recognize phonetic categories from syllable-sized continuous acoustic signals of connected speech without intermediate featural representations. We used Support Vector Machine (SVM) and Self-organizing Map (SOM) to simulate tone perception in Mandarin, by either directly processing f0 trajectories, or extracting various tonal features. The results show that direct tone recognition not only yields better performance than any of the feature extraction schemes, but also requires less computational power. These results suggest that prior extraction of features is unlikely the operational mechanism of speech perception

A Movie Recommendation System Based on Differential Privacy Protection

In the past decades, the ever-increasing popularity of the Internet has led to an explosive growth of information, which has consequently led to the emergence of recommendation systems. A series of cloud-based encryption measures have been adopted in the current recommendation systems to protect users’ privacy. However, there are still many other privacy attacks on the local devices. Therefore, this paper studies the encryption interference of applying a differential privacy protection scheme on the data in the user’s local devices under the assumption of an untrusted server. A dynamic privacy budget allocation method is proposed based on a localized differential privacy protection scheme while taking the specific application scene of movie recommendation into consideration. What is more, an improved user-based collaborative filtering algorithm, which adopts a matrix-based similarity calculation method instead of the traditional vector-based method when computing the user similarity, is proposed. Finally, it was proved by experimental results that the differential privacy-based movie recommendation system (DP-MRE) proposed in this paper could not only protect the privacy of users but also ensure the accuracy of recommendations