Schisandrin C enhances type I IFN response activation to reduce tumor growth and sensitize chemotherapy through antitumor immunity

With the advancing comprehension of immunology, an increasing number of immunotherapies are being explored and implemented in the field of cancer treatment. The cGAS-STING pathway, a crucial element of the innate immune response, has been identified as pivotal in cancer immunotherapy. We evaluated the antitumor effects of Schisandra chinensis lignan component Schisandrin C (SC) in 4T1 and MC38 tumor-bearing mice, and studied the enhancing effects of SC on the cGAS-STING pathway and antitumor immunity through RNA sequencing, qRT-PCR, and flow cytometry. Our findings revealed that SC significantly inhibited tumor growth in models of both breast and colon cancer. This suppression of tumor growth was attributed to the activation of type I IFN response and the augmented presence of T cells and NK cells within the tumor. Additionally, SC markedly promoted the cGAS-STING pathway activation induced by cisplatin. In comparison to cisplatin monotherapy, the combined treatment of SC and cisplatin exhibited a greater inhibitory effect on tumor growth. The amplified chemotherapeutic efficacy was associated with an enhanced type I IFN response and strengthened antitumor immunity. SC was shown to reduce tumor growth and increase chemotherapy sensitivity by enhancing the type I IFN response activation and boosting antitumor immunity, which enriched the research into the antitumor immunity of S. chinensis and laid a theoretical basis for its application in combating breast and colon cancer

Glycyrrhiza uralensis polysaccharides ameliorates cecal ligation and puncture-induced sepsis by inhibiting the cGAS-STING signaling pathway

Ethnopharmacological relevance:G. uralensis Fisch. (Glycyrrhiza uralensis) is an ancient and widely used traditional Chinese medicine with good efficacy in clearing heat and detoxifying action. Studies suggest that Glycyrrhiza Uralensis Polysaccharides (GUP), one of the major components of G. uralensis, has anti-inflammatory, anti-cancer and hepatoprotective effects., but its exact molecular mechanism has not been explored in depth.Aim of the study: Objectives of our research are about exploring the anti-inflammatory role of GUP and the mechanisms of its action.Materials and methods: ELISA kits, Western blotting, immunofluorescence, quantitative real-time PCR, immunoprecipitation and DMXAA-mediated STING activation mice models were performed to investigate the role of GUP on the cGAS-STING pathway. To determine the anti-inflammatory effects of GUP, cecal ligation and puncture (CLP) sepsis models were employed.Results: GUP could effectively inhibit the activation of the cGAS-STING signaling pathway accompany by a decrease the expression of type I interferon-related genes and inflammatory factors in BMDMs, THP-1, and human PBMCs. Mechanistically, GUP does not affect the oligomerization of STING, but affects the interaction of STING with TBK1 and TBK1 with IRF3. Significantly, GUP had great therapeutic effects on DMXAA-induced agonist experiments in vivo as well as CLP sepsis in mice.Conclusion: Our studies suggest that GUP is an effective inhibitor of the cGAS-STING pathway, which may be a potential medicine for the treatment of inflammatory diseases mediated by the cGAS-STING pathway

Unhappy patients are not alike: Content analysis of the negative comments from China's good doctor website

Background: With the rise in popularity of Web 2.0 technologies, the sharing of patient experiences about physicians on online forums and medical websites has become a common practice. However, negative comments posted by patients are considered to be more influential by other patients and physicians than those that are satisfactory. Objective: The aim of this study was to analyze negative comments posted online about physicians and to identify possible solutions to improve patient satisfaction, as well as their relationship with physicians. Methods: A Java-based program was developed to collect patient comments on the Good Doctor website, one of the most popular online health communities in China. A total of 3012 negative comments concerning 1029 physicians (mean 2.93 [SD 4.14]) from 5 highly ranked hospitals in Beijing were extracted for content analysis. An initial coding framework was constructed with 2 research assistants involved in the codification. Results: Analysis, based on the collected 3012 negative comments, revealed that unhappy patients are not alike and that their complaints cover a wide range of issues experienced throughout the whole process of medical consultation. Among them, physicians in Obstetrics and Gynecology (606/3012, 20.12%; P=.001) and Internal Medicine (487/3012, 16.17%; P=.80) received the most negative comments. For negative comments per physician, Dermatology and Sexually Transmitted Diseases (mean 5.72, P<.001) and Andrology (mean 5, P=.02) ranked the highest. Complaints relating to insufficient medical consultation duration (577/3012, 19.16%), physician impatience (527/3012, 17.50%), and perceived poor therapeutic effect (370/3012, 12.28%) received the highest number of negative comments. Specific groups of people, such as those accompanying older patients or children, traveling patients, or very important person registrants, were shown to demonstrate little tolerance for poor medical service. Conclusions: Analysis of online patient complaints provides an innovative approach to understand factors associated with patient dissatisfaction. The outcomes of this study could be of benefit to hospitals or physicians seeking to improve their delivery of patient-centered services. Patients are expected to be more understanding of overloaded physicians' workloads, which are impacted by China's stretched medical resources, as efforts are made to build more harmonious physician-patient relationships.National Natural Science Foundation of China; Hubei Social Science Foundation; Fundamental Research Funds for the Central Universitie

Population response of intestinal microbiota to acute Vibrio alginolyticus infection in half-smooth tongue sole (Cynoglossus semilaevis)

IntroductionVibriosis causes enormous economic losses of marine fish. The present study investigated the intestinal microbial response to acute infection of half-smooth tongue sole with different-dose Vibrio alginolyticus within 72 h by metagenomic sequencing.MethodsThe inoculation amount of V. alginolyticus for the control, low-dose, moderate-dose, and high-dose groups were 0, 8.5 × 101, 8.5 × 104, and 8.5 × 107 cells/g respectively, the infected fish were farmed in an automatic seawater circulation system under a relatively stable temperature, dissolved oxygen and photoperiod, and 3 ~ 6 intestinal samples per group with high-quality DNA assay were used for metagenomics analysis.ResultsThe acute infections with V. alginolyticus at high, medium, and low doses caused the change of different-type leukocytes at 24 h, whereas the joint action of monocytes and neutrophils to cope with the pathogen infection only occurred in the high-dose group at 72 h. The metagenomic results suggest that a high-dose V. alginolyticus infection can significantly alter the intestinal microbiota, decrease the microbial α-diversity, and increase the bacteria from Vibrio and Shewanella, including various potential pathogens at 24 h. High-abundance species of potential pathogens such as V. harveyii, V. parahaemolyticus, V. cholerae, V. vulnificus, and V. scophthalmi exhibited significant positive correlations with V. alginolyticus. The function analysis revealed that the high-dose inflection group could increase the genes closely related to pathogen infection, involved in cell motility, cell wall/ membrane/envelope biogenesis, material transport and metabolism, and the pathways of quorum sensing, biofilm formation, flagellar assembly, bacterial chemotaxis, virulence factors and antibiotic resistances mainly from Vibrios within 72 h.DiscussionIt indicates that the half-smooth tongue sole is highly likely to be a secondary infection with intestinal potential pathogens, especially species from Vibrio and that the disease could become even more complicated because of the accumulation and transfer of antibiotic-resistance genes in intestinal bacteria during the process of V. alginolyticus intensified infection

SMRT bus drivers’ strike : examining the legalities and implications on society.

The SMRT 2012 bus drivers’ strike apparently ended Singapore’s quarter century record of industrial peace. The strike spotlighted global and domestic scrutiny on Singapore’s swift handling of the disruption. The incident presents a valuable opportunity for a critical study of Singapore’s reaction to the labour unrest and questions the necessity and utility of approaching the problem from the angle of a strike. This report begins with an overview of modern Singapore’s plaque of strikes in the fifties and sixties which augured an unprecedented period of industrial peace. An examination of the legal, social, economic and political implications of the SMRT strike suggests that the recent labelling of the unrest as a strike was perhaps unnecessary and imprudent since the ministerial declaration of the unrest as a strike brings with it attendant negative connotations of punishment rather than conciliation and negotiation, masking deeper issues of unfair work conditions and practices. Furthermore, the declaration of strike is a judicial and not executive prerogative and is a matter not lightly exercised. The paper juxtaposes the 1980 Singapore Airlines strike, which is not too dissimilar to the SMRT strike, and argues an alternative precedent and approach in managing the labour unrest without the need to resort to the ‘sledgehammer’ declaration of a strike. By challenging the decisions made by various stakeholders, this study highlights a deeper underlying problem that needs to be addressed. This paper concludes with recommendations on how matters could be better handled by the respective stakeholders of the government, the trade union, the employer and the employee.BUSINES

Outcome of Extracorporeal Shock Wave Therapy for Insertional Achilles Tendinopathy with and without Haglund’s Deformity

Purpose. To compare the results of extracorporeal shock wave therapy (ESWT) for insertional Achilles tendinopathy (IAT) with or without Haglund’s deformity. Methods. Between September 2014 and May 2015, all patients who underwent ESWT were retrospectively enrolled in this study. A total of 67 patients were available for follow-up and assigned into nondeformtiy group (n=37) and deformtiy group (n=30). Clinical outcomes were evaluated by VISA-A Score and 6-point Likert scale. Results. The VISA-A score increased in both groups, from 49.57±9.98 at baseline to 83.86±8.59 at 14.5±7.2 months after treatment in nondeformity group (P<0.001) and from 48.70±9.38 at baseline to 67.78±11.35 at 15.3±6.7 months after treatment in deformity group (P<0.001). However, there was a greater improvement in VISA-A Score for the nondeformity group compared with deformity group (P=0.005). For the 6-point Likert scale, there were decreases from 3.92±0.80 at baseline to 1.57±0.73 at the follow-up time point in nondeformity group (P<0.001) and from 4.0±0.76 at baseline to 2.37±1.03 at the follow-up time point in deformity group (P<0.001). There was no significant difference in improvement of the 6-point Likert scale between both groups (P=0.062). Conclusions. ESWT resulted in greater clinical outcomes in patients without Haglund’s deformity compared with patients with Haglund’s deformity

Establishment of a Recombinant AAV2/HBoV1 Vector Production System in Insect Cells

We have previously developed an rAAV2/HBoV1 vector in which a recombinant adeno-associated virus 2 (rAAV2) genome is pseudopackaged into a human bocavirus 1 (HBoV1) capsid. Recently, the production of rAAV2/HBoV1 in human embryonic kidney (HEK) 293 cells has been greatly improved in the absence of any HBoV1 nonstructural proteins (NS). This NS-free production system yields over 16-fold more vectors than the original production system that necessitates NS expression. The production of rAAV with infection of baculovirus expression vector (BEV) in the suspension culture of Sf9 insect cells is highly efficient and scalable. Since the replication of the rAAV2 genome in the BEV system is well established, we aimed to develop a BEV system to produce the rAAV2/HBoV1 vector in Sf9 cells. We optimized the usage of translation initiation signals of the HBoV1 capsid proteins (Cap), and constructed a BEV Bac-AAV2Rep-HBoV1Cap, which expresses the AAV2 Rep78 and Rep52 as well as the HBoV1 VP1, VP2, and VP3 at the appropriate ratios. We found that it is sufficient as a trans helper to the production of rAAV2/HBoV1 in Sf9 cells that were co-infected with the transfer Bac-AAV2ITR-GFP-luc that carried a 5.4-kb oversized rAAV2 genome with dual reporters. Further study found that incorporation of an HBoV1 small NS, NP1, in the system maximized the viral DNA replication and thus the rAAV2/HBoV1 vector production at a level similar to that of the rAAV2 vector in Sf9 cells. However, the transduction potency of the rAAV2/HBoV1 vector produced from BEV-infected Sf9 cells was 5&ndash;7-fold lower in polarized human airway epithelia than that packaged in HEK293 cells. Transmission electron microscopy analysis found that the vector produced in Sf9 cells had a high percentage of empty capsids, suggesting the pseudopackage of the rAAV2 genome in HBoV1 capsid is not as efficient as in the capsids of AAV2. Nevertheless, our study demonstrated that the rAAV2/HBoV1 can be produced in insect cells with BEVs at a comparable yield to rAAV, and that the highly efficient expression of the HBoV1 capsid proteins warrants further optimization

Evolutionary Game Analysis of Government and Enterprise Behavior Strategies in Public-Private-Partnership Farmland Consolidation

To improve the implementation effect of farmland consolidation (FC) and promote the development of agricultural modernization, the Chinese government has vigorously promoted the application of the public-private-partnership for farmland consolidation (PPP-FC). However, many conflicts of interest among stakeholders exist in PPP-FC. Especially in the implementation stage of PPP-FC, most private enterprises probably prefer to decrease the costs of construction to increase the profits when government incentives and supervision are insufficient. Based on this, this paper constructs an evolutionary game model between the government and the enterprises to explore the motivations of the enterprises&rsquo; speculative behaviors, the interaction mechanism and the evolutionary stability strategies of both parties and uses numerical simulations to visually analyze the effectiveness of the incentive mechanism and the strategic change of both sides. Our results show that (1) the enterprise&rsquo;s farmland operating income is the decisive factor that affects behavioral choices: the situation for the income of a low-effort strategy is greater than that of a high-effort strategy is the root cause of speculative behavior; (2) the incentive mechanism can simultaneously affect the decision-making direction and speed of both the government and the enterprises, especially punishment which can effectively regulate the behaviors of the enterprises; (3) government regulation costs and officials&rsquo; desire for promotion are important factors affecting their strategic choices: regulation costs negatively impact the government&rsquo;s plans to adopt an incentive strategy and the promotion desire positively promotes the government implementing incentive measures for the enterprises; and (4) the supervision level of farmers is an important factor that affects the strategic choices of both the government and the enterprises: farmers supervision is an effective remedy for inadequate government regulation and constrains the government&rsquo;s behavior. Finally, the paper proposes corresponding policy recommendations to improve the implementation effect of PPP-FC and also provides an important reference for other developing countries to formulate PPP-FC incentive mechanisms

Effects of Fertilizer Reduction and Straw Application on Dynamic Changes of Phosphorus in Overlying and Leaching Water in Rice Fields

In the process of rice cultivation, fertilizer reduction can effectively reduce the concentration of phosphorus (P) in overlying water and leaching water. In this study, the variation characteristics of P in overlying and leaching water under the conditions of fertilizer reduction and straw application and its impact on the environment were studied through a two-season rice field experiment. Four treatments were set, including no fertilizer without straw (CK), conventional fertilization (CF), 20% reduction in nitrogen (N) and P fertilization (RF), and 20% reduction in N and P fertilization with the wheat straw (RFWS). The results showed that RF could effectively reduce the risk of P loss due to its ability to decrease the concentration of P in overlying and leaching water. RFWS increased P concentrations in overlying and leaching water of rice fields. Total dissolved phosphorus (TDP) was the main form of total phosphorus (TP), and soluble reactive phosphorus (SRP) was the main form of TDP. The concentration of TP, TDP, and SRP in the overlying and leaching water peaked on the first day after fertilization, and then gradually decreased. The high-risk period of P loss was 0 to 10 days after fertilization. This study could provide appropriate strategies to reduce the risk of P loss during local rice cultivation and protect local water resources from eutrophication