MAC3A and MAC3B mediate degradation of the transcription factor ERF13 and thus promote lateral root emergence.

Lateral roots (LRs) increase root surface area and allow plants greater access to soil water and nutrients. LR formation is tightly regulated by the phytohormone auxin. Whereas the transcription factor ETHYLENE-RESPONSIVE ELEMENT BINDING FACTOR13 (ERF13) prevents LR emergence in Arabidopsis (Arabidopsis thaliana), auxin activates MITOGEN-ACTIVATED PROTEIN KINASE14 (MPK14), which leads to ERF13 degradation and ultimately promotes LR emergence. In this study, we discovered interactions between ERF13 and the E3 ubiquitin ligases MOS4-ASSOCIATED COMPLEX 3A (MAC3A) and MAC3B. As MAC3A and MAC3B gradually accumulate in the LR primordium, ERF13 levels gradually decrease. We demonstrate that MAC3A and MAC3B ubiquitinate ERF13, leading to its degradation and accelerating the transition of LR primordia from stages IV to V. Auxin enhances the MAC3A and MAC3B interaction with ERF13 by facilitating MPK14-mediated ERF13 phosphorylation. In summary, this study reveals the molecular mechanism by which auxin eliminates the inhibitory factor ERF13 through the MPK14-MAC3A and MAC3B signaling module, thus promoting LR emergence.

Non-canonical AUX/IAA protein IAA33 competes with canonical AUX/IAA repressor IAA5 to negatively regulate auxin signaling.

The phytohormone auxin controls plant growth and development via TIR1-dependent protein degradation of canonical AUX/IAA proteins, which normally repress the activity of auxin response transcription factors (ARFs). IAA33 is a non-canonical AUX/IAA protein lacking a TIR1-binding domain, and its role in auxin signaling and plant development is not well understood. Here, we show that IAA33 maintains root distal stem cell identity and negatively regulates auxin signaling by interacting with ARF10 and ARF16. IAA33 competes with the canonical AUX/IAA repressor IAA5 for binding to ARF10/16 to protect them from IAA5-mediated inhibition. In contrast to auxin-dependent degradation of canonical AUX/IAA proteins, auxin stabilizes IAA33 protein via MITOGEN-ACTIVATED PROTEIN KINASE 14 (MPK14) and does not affect IAA33 gene expression. Taken together, this study provides insight into the molecular functions of non-canonical AUX/IAA proteins in auxin signaling transduction.

The response of LncRNAs associated with photosynthesis-and pigment synthesis-related genes to green light in Chlamydomonas reinhardtii.

The quality of light is an important abiotic factor that affects the growth and development of green plants. Ultraviolet, red, blue, and far-red light all have demonstrated roles in regulating green plant growth and development, as well as light morphogenesis. However, the mechanism underlying photosynthetic organism responses to green light throughout the life of them are not clear. In this study, we exposed the unicellular green alga Chlamydomonas reinhardtii to green light and analyzed the dynamics of transcriptome changes. Based on the whole transcriptome data from C. reinhardtii, a total of 9974 differentially expressed genes (DEGs) were identified under green light. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these DEGs were mainly related to "carboxylic acid metabolic process," "enzyme activity," "carbon metabolism," and "photosynthesis and other processes." At the same time, 253 differentially expressed long non-coding RNAs (DELs) were characterized as green light responsive. We also made a detailed analysis of the responses of photosynthesis- and pigment synthesis-related genes in C. reinhardtii to green light and found that these genes exhibited obvious dynamic expression. Lastly, we constructed a co-expression regulatory network, comprising 49 long non-coding RNAs (lncRNAs) and 20 photosynthesis and pigment related genes, of which 9 mRNAs were also the predicted trans/cis-targets of 8 lncRNAs, these results suggested that lncRNAs may affect the expression of mRNAs related to photosynthesis and pigment synthesis. Our findings give a preliminary explanation of the response mechanism of C. reinhardtii to green light at the transcriptional level.

Research on government regulation methods for the spatial layout of retail pharmacies: practice in Shanghai, China.

BACKGROUND: In China, retail pharmacies are critical sources for obtaining medications and play a vital role in residents' daily access to drugs and treatment of common illnesses. Effectively guiding the placement of these pharmacies in areas of need through government regulation is crucial for enhancing medication access. In this study, we used population and retail pharmacy spatial distribution data from Shanghai to design guidance and supplementary methods for optimizing the spatial layout of retail pharmacies and medical insurance designated pharmacies based on regional characteristics. METHODS: Population distribution, road traffic network, administrative division and retail pharmacy data from Shanghai in 2018 were collected from relevant government departments. ArcGIS 10.3 was used to map the retail pharmacies and population distribution. Based on the spatial distribution of population and the service standards of pharmacies, service circles with insufficient pharmacies were identified, and supplementary methods for retail pharmacies and medical insurance designated pharmacies were developed. RESULTS: In 2018, Shanghai had 3009 retail pharmacies, each serving an average of 6412 residents. The city was divided into 2188 basic pharmaceutical service circles, each within a 15-minute walking distance. The results indicated that there were 1387 service circles without any pharmacies, 151 of which had populations exceeding 5000. Additionally, 356 service circles had pharmacies but lacked medical insurance designated ones. After supplementation, 841 retail pharmacies were planned to be added in residential areas. Compared with before, the coverage area and population served of the pharmacies increased significantly. CONCLUSIONS: This study mapped the spatial distribution of population and retail pharmacies in Shanghai, and designed government guidance and supplementary methods for optimizing the layout of retail pharmacies. The findings offer valuable insights for government agencies in low- and middle-income countries to improve the spatial distribution of retail pharmacies.

Impacts of Multiple and One-time Root Canal Therapy on Immune and Inflammatory Response in Endodontic Patients.

Background: Root canal therapy is a widely adopted clinical approach for managing endodontic diseases. However, patients undergoing multiple root canal treatments face an increased risk of reinfection, complicating treatment outcomes. Objective: This study aims to evaluate the effects of both multiple and one-time root canal therapy on the immune and inflammatory responses in endodontic patients. Design: A randomized controlled study was conducted. Setting: The research was carried out at the 8th People's Hospital of Shanghai. Participants: A total of 100 endodontic patients admitted to the Stomatology Department of the hospital from January 2021 to December 2022 were randomly allocated to either the study group or the control group, with each group consisting of 50 cases. Interventions: The control group received multiple root canal therapy, while the study group underwent one-time root canal treatment. Primary Outcome Measures: (1) Clinical treatment effectiveness, (2) pain intensity, (3) levels of inflammatory factors, (4) oral immune factor levels, (5) oral health-related quality of life, and (6) occurrence of adverse reactions were assessed. Results: The study group demonstrated a significantly higher total effective rate compared to the control group (P < .05). Post-treatment, the study group exhibited lower pain scores, reduced levels of inflammatory factors, improved oral health-related quality of life, and fewer adverse reactions compared to the control group (P < .05). Additionally, the study group showed elevated levels of lysozyme, human ß-defensin 2, and secretory Immunoglobulin A compared to the control group (P < .05). Conclusions: One-time root canal therapy in endodontic patients yields superior outcomes, effectively reducing adverse reactions and inflammatory factor levels, enhancing chewing function, alleviating pain, and demonstrating clinical utility. This study underscores the importance and efficacy of adopting a one-time root canal treatment approach in endodontic practice.

Aluminum-maltol induced oxidative stress and reduced AMPK activity via BCK-related energy supply failure in C6 cell.

Aluminum (Al) exposure significantly interferes with the energy supply in astrocytes, which may be a potential mechanism of Al-induced neurotoxicity. This study was designed to explore the mechanisms of Al-induced energy supply impairment in rat C6 astroglioma cell line. Aluminum-maltolate (Al(mal)3) (0.1 mM, 24 h) exposure significantly decreased brain-type creatine kinase (BCK) co-localization with the endoplasmic reticulum (ER) and resulted in mitochondrial dysfunctions, accompanied by a decrease in AMPK phosphorylation. The results of molecular docking showed that Al(mal)3 increased BCK's hydrophobicity and hindered the localization movement of BCK between subcells·H2O2 co-administration was found to exacerbate mitochondrial dysfunction, Ca2+ dyshomeostasis, and apoptosis. After treated with Al(mal)3, additional oxidative stress contributed to BCK activity inhibition but did not promote a further decrease in AMPK phosphorylation. The activation of p-AMPK by its agonist can partially restore mitochondrial function, BCK activity, and ER-localized-BCK levels in Al(mal)3-treated astrocytes. In summary, Al exposure resulted in a sustained depletion of the mitochondrial and antioxidant systems, which was associated with reduced p-AMPK activity and decreased ER-localized-BCK levels in astrocytes. This study provides a theoretical basis for exploring the mechanisms of neurotoxicity induced by Al exposure.

Unveiling hormone-stimulated gene mechanisms in prostate cancer: A prognostic model, immune infiltration analysis, and drug sensitivity study.

Hormones promote the progression of prostate cancer (PRCA) through the activation of a complex regulatory network. Inhibition of hormones or modulation of specific network nodes alone is insufficient to suppress the entire oncogenic network. Therefore, it is imperative to elucidate the mechanisms underlying the occurrence and development of PRCA in order to identify reliable diagnostic markers and therapeutic targets. To this end, we used publicly available data to analyze the potential mechanisms of hormone-stimulated genes in PRCA, construct a prognostic model, and assess immune infiltration and drug sensitivity. The single-cell RNA-sequencing data of PRCA were subjected to dimensionality reduction clustering and annotation, and the cells were categorized into two groups based on hormone stimulus-related scores. The differentially expressed genes between the two groups were screened and incorporated into the least absolute shrinkage and selection operator machine learning algorithm, and a prognostic model comprising six genes (ZNF862, YIF1A, USP22, TAF7, SRSF3, and SPARC) was constructed. The robustness of the model was validation through multiple methods. Immune infiltration scores in the two risk groups were calculated using three different algorithms. In addition, the relationship between the model genes and immune cell infiltration, and that between risk score and immune cell infiltration were analyzed. Drug sensitivity analysis was performed for the model genes and risk score using public databases to identify potential candidate drugs. Our findings provide novel insights into the mechanisms of hormone-stimulated genes in PRCA progression, prognosis, and drug screening.

Perceived HRM and turnover intentions of elderly care workers: perspective from person-job fit and institutional ownership.

BACKGROUND: Although the phenomenon of high turnover rate in the elderly care industry has existed for a long time, there are few studies that have constructed frameworks to comprehensively analyze the strength of the effects of various factors on the turnover intention of elderly care workers.. This study analyzed the impact of different types of perceived human resource management practices on elderly care workers' turnover intentions and whether this relationship is moderated by person-job fit and ownership of elderly care institutions. METHODS: This is a cross-sectional and regional survey study. The study included questionnaire survey data from a total of 305 elderly care workers from 42 elderly care institutions in 21 provinces in China during June to September 2021. Descriptive statistics, Pearson correlation coefficient, multiple regression, and heterogeneity analyses were performed. RESULTS: Perceived work environment ( ß =-0.5164, p< 0.01), perceived occupational protection ( ß =-0.3390, p< 0.01), perceived welfare benefits ( ß = -0.2620, p< 0.01) and perceived competency training ( ß = -0.1421, p< 0.1) were all significantly and negatively related to turnover intentions, the quality of perceived work environment has the greatest impact on elderly care workers' turnover intentions. Under the moderating effects of person-job fit and ownership of elderly care institutions, there existed heterogeneity between perceived human resource management and turnover intentions among elderly care workers. High level of person-job fit and elderly care institutions' public feature can effectively weaken the negative impact of each type of perceived human resource management on turnover intention among elderly care workers. CONCLUSIONS: The managers of elderly care institutions should optimize the management mechanism, typically pay attention to elderly care workers' working environment, formulate and improve the professional standards and job requirements for elderly care workers, promote the public welfare value of nursing care services, and strengthen the sense of honor and responsibility of elderly care workers to reduce the turnover rate.

New insight of Mn(III) in δ-MnO2 for peroxymonosulfate activation reaction: Via direct electron transfer or via free radical reactions.

Due to the increasing of industrial plastic waste and its refractory characteristics, it is extremely urgent to develop new degradation technology and environmentally friendly catalyst for industrial plastic waste. Manganese oxides are one of the most promising candidates for the catalytic degradation of plastic wastes. However, an improved understanding of the structural properties affecting their catalytic activity is required for high-efficient wastewater treatment. We herein report the surface reactivity effects of δ-MnO2 structural defects with regards to Bisphenol A (BPA) degradation/probe in the presence of peroxymonosulfate (PMS). Four δ-MnOx samples with different Mn(III) contents (different Mn(III)-deficient sample) were prepared and their structural properties as well as surface reactivity were characterized by batch test, ESR and XAFS analysis. For the Mn(III)-deficient sample, BPA removal was principally affected by direct electron transfer, with the adsorbed BPA degraded following hydroxylation. In contrast, a small fraction of Mn(III) substitution in δ-MnO2 could significantly encouraged the activation of PMS to produce SO4-☐and ☐OH, and a BPA degradation via beta scission. Moreover, the Mn(III)-rich δ-MnO2 demonstrate a high BPA removal rate even with a low sample load, which performed well following a reuse of five times. Our results provide a new way for the improvement of δ-MnO2 activity for the use of industrial plastic wastes treatment.

Muscle cytotoxicity and immuno-reactivity analysis of the porous carbon nanospheres fabricated by high temperature calcination.

Carbon-based nanomaterials have a high specific surface area, biocompatibility, and controlled mesopore structures. These characteristics make carbon nanospheres excellent carriers for drugs, biological dyes, photosensitizers, etc. Nevertheless, little is known about the impact of topological features on the surface of carbon nanomaterials on their in vivo immunoreactivity. In this study, we fabricated mesoporous carbon nanoparticles (MCNs) and solvent-processable carbon vesicles (CVs) by high-temperature calcination. The hematoxylin and eosin (H&E) staining suggested CVs' relatively poor dispersion capacity compared to MCNs and carbon precursors (CPs), leading to more severe muscle inflammation and necrosis. Immunostaining and Fluorescence Activated Cell Sorter (FACS) analysis further showed that both MCNs and CVs triggered a transient immune response in transplanted muscle and muscle-draining lymph nodes, but did not alter muscle resistance to exogenous viruses. In conclusion, this study provides insights into how carbon nanoparticles modulate the activation of immune responses in vivo.

Progress in the study of intragastric occupancy device for weight reduction. / èƒƒå† å å®¹è£ ç½®å‡é‡çš„ç ”ç©¶è¿›å±•.

Obesity is a global public health problem that imposes a heavy economic burden on society. The current main strategies for treating obesity include lifestyle interventions, pharmacological treatments, endoscopic treatments and metabolic surgery. With the development of medical technology, weight reduction by intragastric occupancy devices represented by intragastric balloons and intragastric capsules are gradually emerging. Intragastric balloons are used to reduce weight by occupying the volume of the stomach with balloons filled with different volumes of gas or liquid, among which ReShape, Orbera, Obalon, Elipse and Spatz balloons are gradually used in patients with mild to moderate obesity due to their non-invasive, high safety and reusable advantages. Intragastric capsules are recommended in overweight and obese patients for weight loss through hydrogels with transient superabsorbent swelling properties and completely noninvasive. Both approaches achieve weight loss by limiting gastric volume, increasing satiety and reducing food intake. Despite the presence of adverse gastrointestinal events associated with nausea, vomiting, and abdominal distention, they offer new ideas for the non-invasive clinical treatment of obesity.

C9orf72 knockdown alleviates hepatic insulin resistance by promoting lipophagy.

Insulin resistance (IR) attributed by the deficiency of lipophagy, is an abnormal state of downregulation of insulin-mediated glucose uptake and use into the liver. Chromosome 9 open reading frame 72 (C9orf72) variously modulates autophagy. We investigated the role and the downstream pathway of C9orf72 in hepatic IR. We found that C9orf72 knockdown alleviated hepatic IR by lipophagy promotion in T2DM mice and in IR-challenged hepatocytes in vitro. C9orf72 interacted with and activated cell division cycle 42 (Cdc42) protein in IR-challenged hepatocytes, Which in turn, inhibits lipophagy by promoting neural Wiskott-Aldrich syndrome protein (N-WASP) expression and activation. C9orf72 inhibited lipophagy by activating the Cdc42/N-WASP axis to facilitate hepatic IR; therefore, the knockdown of C9orf72 may be potentially therapeutic for the treatment of IR.

Myeloarchitectonic Asymmetries of Language Regions in the Human Brain.

One prominent theory in neuroscience and psychology assumes that cortical regions for language are left hemisphere lateralized in the human brain. In the current study, we used a novel technique, quantitative magnetic resonance imaging (qMRI), to examine interhemispheric asymmetries in language regions in terms of macromolecular tissue volume (MTV) and quantitative longitudinal relaxation time (T1) maps in the living human brain. These two measures are known to reflect cortical myeloarchitecture from the microstructural perspective. One hundred and fifteen adults (55 male, 60 female) were examined for their myeloarchitectonic asymmetries of language regions. We found that the cortical myeloarchitecture of inferior frontal areas including the pars opercularis, pars triangularis, and pars orbitalis is left lateralized, while that of the middle temporal gyrus, Heschl's gyrus, and planum temporale is right lateralized. Moreover, the leftward lateralization of myelination structure is significantly correlated with language skills measured by phonemic and speech tone awareness. This study reveals for the first time a mixed pattern of myeloarchitectonic asymmetries, which calls for a general theory to accommodate the full complexity of principles underlying human hemispheric specialization.

Evaluation and countermeasures of contracted services of Chinese family doctors from demanders' point of view - a case study of a city.

BACKGROUND: The "gatekeepers" for residents' health are their family doctors. The implementation of contracted services provided by family doctors is conducive to promoting hierarchical diagnosis and treatment and achieving the objective of providing residents comprehensive and full-cycle health services. Since its implementation in 2016, the contract service system for Chinese family doctors has yielded a number of results while also highlighting a number of issues that require further investigation. Consequently, the purpose of this study is to assess the impact of family doctors' contracted services in a Chinese city from the perspective of demanders (i.e., contracted residents), identify the weak links, and then propose optimization strategies. METHODS: In this study, a city in Shandong Province, China was selected as the sample city. In January 2020, 1098 contracted residents (including 40.5% men and 59.5% women) from 18 primary medical institutions (including township health centers and community health centers) were selected for on-site investigation. Take the PCAT-AS(Adult Short) scale revised in Chinese as the research tool to understand the medical experience of contracted residents in primary medical institutions, and interview some family doctors and residents to obtain more in-depth information. RESULTS: Among the four core dimensions of PCAT-AS, the score of Continuous was the highest (3.44 ± 0.58); The score of Coordinated was the lowest (3.08 ± 0.66); Among the three derived dimensions, the score of Family-centeredness was the highest (3.33 ± 0.65); The score of Culturally-competent was the lowest (2.93 ± 0.77). The types of contracting institutions, residents' age, marital status, occupation, and whether chronic diseases are confirmed are the influencing factors of PCAT scores. CONCLUSION: The family doctors' contracted services in the city has achieved certain results. At the same time, there are still some problems, such as difficult access to outpatient services during non-working hours, incomplete service items, an imperfect referral system, and inadequate utilization of traditional Chinese medicine services, it is recommended that the government continue to enhance and increase its investment in relevant policies and funds. Primary medical institutions should improve the compensation mechanism for family doctors and increase their work enthusiasm, improve and effectively implement the two-way referral system, gradually form an orderly hierarchical pattern of medical treatment, provide diversified health services in accordance with their own service capacity and the actual needs of residents, and improve the utilization rate of traditional Chinese medicine services in primary medical institutions.

Serum Extracellular Vesicles Attenuate Cardiomyocyte Injury Induced by Hypoxic/Reoxygenation by Regulating miR-1229-5p.

Ischemic heart disease and the resulting heart failure remain the leading causes of death and disability worldwide. This study aimed to investigate the role of miR-1229-5p in serum extracellular vesicles (EVs) mediated myocardial protection by constructing a hypoxia/reoxygenation model (HR) in H9c2 cells. Cardiomyocytes were cultured and divided into different treatment groups: control group, HR group, serum-EVs group, and serum-EVs + miR-1229-5p inhibitor group. The expression levels of miR-1229-5p were detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The changes in cell proliferation and apoptosis were detected by MTT assay and flow cytometry. The myocardial injury-related indicators, cardiac troponin I (cTnI), creatinine kinase MB (CK-MB), and lactate dehydrogenase (LDH), were measured by enzyme-linked immunosorbent assay (ELISA). Finally, the luciferase reporter assay was used to verify the miR-1229-5p target. The proliferation of myocardial cells in the HR group was reduced, the number of apoptotic cells was increased, and myocardial injury indicators concentration was decreased. Transfection of miR-1229-5p inhibitor under serum-EVs treatment reduced the protective effect of serum-EVs on myocardial cell injury, decreased cell proliferation, increased the number of apoptotic cells, and increased myocardial injury indicator concentration. Additionally, FOXO4 may be the target of miR-1229-5p. Our data suggest that serum-EVs alleviate HR-induced cardiomyocyte injury by regulating miR-1229-5p/FOXO4.

Tricyano-Methylene-Pyridine Based High-Performance Aggregation-Induced Emission Photosensitizer for Imaging and Photodynamic Therapy.

Photosensitizers equipped with high reactive oxygen species (ROS) generation capability and bright emission are essential for accurate tumor imaging and precise photodynamic therapy (PDT). However, traditional aggregation-caused quenching (ACQ) photosensitizers cannot simultaneously produce desirable ROS and bright fluorescence, resulting in poor image-guided therapy effect. Herein, we report an aggregation-induced emission (AIE) photosensitizer TCM-Ph with a strong donor-π-acceptor (D-π-A) structure, which greatly separates the HOMO-LUMO distribution and reduces the ΔEST, thereby increasing the number of triplet excitons and producing more ROS. The AIE photosensitizer TCM-Ph has bright near-infrared emission, as well as a higher ROS generation capacity than the commercial photosensitizers Bengal Rose (RB) and Chlorine e6 (Ce6), and can effectively eliminate cancer cells under image guidance. Therefore, the AIE photosensitizer TCM-Ph has great potential to replace the commercial photosensitizers.

A Qa-SNARE complex contributes to soybean cyst nematode resistance via regulation of mitochondria-mediated cell death.

The resistance to Heterodera glycines 1 (Rhg1) locus is widely used by soybean breeders to reduce yield loss caused by soybean cyst nematode (SCN). α-SNAP (α-soluble NSF attachment protein) within Rhg1 locus contributes to SCN resistance by modulation of cell status at the SCN feeding site; however, the underlying mechanism is largely unclear. Here, we identified an α-SNAP-interacting protein, GmSYP31A, a Qa-SNARE (soluble NSF attachment protein receptor) protein from soybean. Expression of GmSYP31A significantly induced cell death in Nicotiana benthamiana leaves, and co-expression of α-SNAP and GmSYP31A could accelerate cell death. Overexpression of GmSYP31A increased SCN resistance, while silencing or overexpression of a dominant-negative form of GmSYP31A increased SCN sensitivity. GmSYP31A expression also disrupted endoplasmic reticulum-Golgi trafficking, and the exocytosis pathway. Moreover, α-SNAP was also found to interact with GmVDAC1D (voltage-dependent anion channel). The cytotoxicity induced by the expression of GmSYP31A could be relieved either with the addition of an inhibitor of VDAC protein, or by silencing the VDAC gene. Taken together, our data not only demonstrate that α-SNAP works together with GmSYP31A to increase SCN resistance through triggering cell death, but also highlight the unexplored link between the mitochondrial apoptosis pathway and vesicle trafficking.

Overexpression of miR-127 Predicts Poor Prognosis and Contributes to the Progression of Papillary Thyroid Cancer by Targeting REPIN1.

Papillary thyroid cancer (PTC) is a major kind of thyroid cancer with increasing recurrence and metastasis. MiR-127 has been demonstrated to play roles in many cancers with dysregulation. However, the function of miR-127 is still unknown. This study aimed to explore a novel biomarker for the progression and prognosis of PTC. A set of 118 patients with PTC were collected from the Affiliated Hospital of Qingdao University. qRT-PCR was used to detect the expression of miR-127 in PTC tissues and cells. The association between miR-127 expression and the clinicopathological features of patients were evaluated by the χ2 test, and the prognostic value of miR-127 was evaluated by Kaplan-Meier analysis and Cox regression analysis. The effect of miR-127 on cell proliferation, migration, and invasion of PTC was analyzed by CCK-8 and transwell assay. miR-127 was found to be upregulated in PTC tissues and cells correlated with the TNM stage and poor prognosis of PTC patients. MiR-127 and the TNM stage were considered as two independent prognostic indicators for PTC. Moreover, overexpression of miR-127 significantly enhanced cell proliferation, migration, and invasion of PTC by targeting REPIN1. miR-127 may be involved in the progression of PTC, which provides a new therapeutic strategy for PTC.

hIgDFc-Ig inhibits B cell function by regulating the BCR-Syk-Btk-NF-κB signalling pathway in mice with collagen-induced arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease targeting the synovium. Previous studies have found that IgD may be a potential target for the treatment of RA. We designed a new type of fusion protein, hIgDFc-Ig (DG), to block the binding of IgD to IgD receptor (IgDR). In this study, we found that DG has a significant therapeutic effect in mice with collagen-induced arthritis (CIA). DG improved the claw of irritation symptoms in these mice, inhibited the pathological changes in spleen and joint tissues, and had a moderating effect on B cell subsets at different inflammatory stages. Moreover, DG could also decrease the levels of IgA, IgD, IgM and IgG subtypes of immunoglobulin in the serum of mice with CIA. In vitro, B cell antigen receptor (BCR) knockout Ramos cells were established using the CRISPR/Cas9 technology to further study the activation of BCR signalling by IgD and the effect of DG. We found that the therapeutic effect of DG in mice with CIA may be achieved by inhibiting the activation of BCR signalling by IgD, which may be related to the activation of Igß. In summary, DG may be a potential biological agent for the treatment of RA and it has broad application prospects in the future.

Trend and equity of general practitioners' allocation in China based on the data from 2012-2017.

BACKGROUND: General practitioners are the gatekeepers of the health of the residents. This study aims to evaluate the trend and equity of general practitioners' allocation from 2012 to 2017 in China and provide a reference for regional health planning and rational distribution of general practitioners. METHODS: We extracted the data of general practitioners from 22 provinces, 5 autonomous regions, and 4 municipalities of mainland China. The population and geographical area were taken from the China Statistical Yearbook. The general practitioners' data were taken from the China Health Statistical Yearbook. Lorenz curve, Gini coefficient, and agglomeration degree were used to analyze the data. RESULTS: The number of general practitioners was 252,717 in 2017, which equates to 1.82 per 10,000 residents, and accounts for 7.45% of the total number of practicing (assistant) doctors. From 2012 to 2017, the population-based Gini coefficient for general practitioners reduced from 0.31 to 0.24, while the geographical area-based Gini coefficient remained unchanged at 0.73. The agglomeration degree based on population increased from 0.72 to 0.73 in the western region including Tibet (0.403) and Shaanxi (0.513). Moreover, in the eastern region the agglomeration degree reduced from 1.477 to 1.329. In the middle region it rose from 0.646 to 0.802. The agglomeration degree based on the geographical area in the western region increased from 0.270 to 0.277 while the values in Tibet, Qinghai, Xinjiang were less than 0.1. In the eastern region, it reduced from 1.447 to 1.329. It increased from 1.149 to 1.423 in the middle region. CONCLUSIONS: The number of general practitioners has increased significantly in China. It has a fair allocation based on population. However, the equity based on geographical area is low and uneven in different regions with large regional differences. In the western region, there is an allocation shortage with respect to population and geographical area. Concerned departments should establish and improve the incentive and performance appraisal mechanisms of general practitioners. The Internet + should be used to empower their service capacity and efficiency. The educational input should be increased for the western region and government should encourage the eastern region to support the western region.