Studies on cell signaling pay more attention to spatial dynamics and how such diverse organization can relate to high order of cellular capabilities. To overview the specificity of cell signaling, we integrated human receptome data with proteome spatial expression profiles to systematically investigate the specificity of receptors and receptor-triggered transduction networks across 62 normal cell types and 14 cancer types. Six percent receptors showed cell-type-specific expression, and 4% signaling networks presented enriched cell-specific proteins induced by the receptors. We introduced a concept of "response context" to annotate the cell-type dependent signaling networks. We found that most cells respond similarly to the same stimulus, as the "response contexts" presented high functional similarity. Despite this, the subtle spatial diversity can be observed from the difference in network architectures. The architecture of the signaling networks in nerve cells displayed less completeness than that in glandular cells, which indicated cellular-context dependent signaling patterns are elaborately spatially organized. Likewise, in cancer cells most signaling networks were generally dysfunctional and less complete than that in normal cells. However, glioma emerged hyper-activated transduction mechanism in malignant state. Receptor ATP6AP2 and TNFRSF21 induced rennin-angiotensin and apoptosis signaling were found likely to explain the glioma-specific mechanism. This work represents an effort to decipher context-specific signaling network from spatial dimension. Our results indicated that although a majority of cells engage general signaling response with subtle differences, the spatial dynamics of cell signaling can not only deepen our insights into different signaling mechanisms, but also help understand cell signaling in disease.
Cell Line ; Databases, Protein ; Gene Expression Profiling ; Humans ; Metabolic Networks and Pathways ; Neoplasms ; metabolism ; pathology ; Proteome ; analysis ; Receptors, Cell Surface ; metabolism ; Receptors, Tumor Necrosis Factor ; metabolism ; Signal Transduction ; Vacuolar Proton-Translocating ATPases ; metabolism

OBJECTIVETo study mRNA expression of receptor activator nuclear factor kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG) in peri-implant tissue during unloading period.

METHODSAn animal model of dental implant was established in 6 male Beagle dogs of 1-2 years old. Bone remodeling was tested at 3, 7, 15, 30, 60 and 90 days since the placement of implants. RANKL and OPG mRNA expression were quantified by real-time polymerase chain reaction (PCR). Then mandibular bones were taken out and the morphological changes were observed by X-ray, bone tissue was tested by immunohistochemistry stain.

RESULTSThe most prominent period of bone remodeling occurred at 7th day after the placement of implants. The expression of RANKL and OPG increased in a time-dependent manner in both soft and hard tissue. After 7 days they gradually decreased.

CONCLUSIONRANKL and OPG can express in soft tissue, and the changing tendency is consistent with the change of bone remodeling, it indicates that RANKL and OPG play an important role in the bone remodeling.

Animals ; Bone Remodeling ; Bone and Bones ; Carrier Proteins ; Dogs ; Male ; NF-kappa B ; Osteoprotegerin ; RANK Ligand ; Receptor Activator of Nuclear Factor-kappa B

ObjectiveTo investigate the mutation and genetic evolution of drug resistance gene of A（H1N1） pdm09 influenza pandemic strain in 2023 in Huzhou City， Zhejiang Province. MethodsRespiratory tract specimens from 2 influenza monitoring hospitals were collected forA（H1N1） pdm09 influenza virus nucleic acid detection. Positive specimens were inoculated with MDCK cells for influenza virus isolation and sequencing. DNA Star 7.1 software and Mega 4.0 software were used to analyze the neuraminidase （NA） enzyme active site and the amino acid sites related to drug resistance in M2 protein. ResultsNucleotide homology and amino acid homology of NA between the isolated and the vaccine strains were 98.87%‒99.22% and 98.94%‒99.36%， respectively. The nucleotide homology range of M gene was 99.07% to 99.85%， and the amino acid homology range was 99.02%‒99.94%. The isolates and vaccine strains belong to the evolutionary clades of 6B.1A.5a.2a. The amino acids at the key sites of the enzyme activity center of NA were still highly conserved， and the 9 key amino acid sites related to NA inhibitor resistance did not change， but some mutations occurred at the non-enzyme active sites in some popular strains. The 5 amino acid sites related to drug resistance of M2 protein were not replaced， but the 31st amino acid sites changed from serine to asparagine. ConclusionThe A（H1N1） pdm09 pandemic strain in Huzhou in 2023 has high homology with the 2023‒2024 vaccine strain recommended by WHO. All endemic strains are resistant to amantadines.

Objective To explore the role of zinc finger protein 36 (ZFP36) in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and preosteoblasts. Methods ZFP36 expression was observed in primary mouse BMSCs and mouse preosteoblasts (MC3T3-E1 cells) during induced osteogenic differentiation. Zfp36-deficient cell models were constructed in the two cells using RNA interference technique and the changes in differentiation capacities of the transfected cells into osteoblasts were observed. Transcriptome sequencing was used to investigate the potential mechanisms of ZFP36 for regulating osteoblast differentiation of the two cells. U0126, a ERK/MAPK signal suppressor, was used to verify the regulatory mechanism of Zfp36 in osteogenic differentiation of Zfp36-deficient cells. Results During the 14-day induction of osteogenic differentiation, both mouse BMSCs and MC3T3-E1 cells exhibited increased expression of ZFP36, and its mRNA expression reached the peak level on Day 7 (P<0.0001). The Zfp36-deficient cell models showed reduced intensity of alkaline phosphatase (ALP) staining and alizarin red staining with significantly lowered expressions of the osteogenic marker genes including Alpl, Sp7, Bglap and Ibsp (P<0.01). Transcriptome sequencing verified the reduction of bone mineralization-related gene expressions in Zfp36-deficient cells and indicated the involvement of ERK signaling in the potential regulatory mechanism of Zfp36. Immunoblotting showed that pERK protein expression increased significantly in Zfp36-deficient cells compared with the control cells. In Zfp36-deficient MC3T3-E1 cells, inhibition of activated ERK/MAPK signaling with U0126 resulted in obviously enhanced ALP staining and significantly increased expressions of osteoblast differentiation markers Runx2 and Bglap (P<0.05). Conclusions ZFP36 is involved in the regulation of osteoblast differentiation of mouse BMSCs and preosteoblasts, and ZFP36 deficiency causes inhibition of osteoblast differentiation of the cells by activating the ERK/MAPK signaling pathway.

Objective To explore the role of zinc finger protein 36 (ZFP36) in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and preosteoblasts. Methods ZFP36 expression was observed in primary mouse BMSCs and mouse preosteoblasts (MC3T3-E1 cells) during induced osteogenic differentiation. Zfp36-deficient cell models were constructed in the two cells using RNA interference technique and the changes in differentiation capacities of the transfected cells into osteoblasts were observed. Transcriptome sequencing was used to investigate the potential mechanisms of ZFP36 for regulating osteoblast differentiation of the two cells. U0126, a ERK/MAPK signal suppressor, was used to verify the regulatory mechanism of Zfp36 in osteogenic differentiation of Zfp36-deficient cells. Results During the 14-day induction of osteogenic differentiation, both mouse BMSCs and MC3T3-E1 cells exhibited increased expression of ZFP36, and its mRNA expression reached the peak level on Day 7 (P<0.0001). The Zfp36-deficient cell models showed reduced intensity of alkaline phosphatase (ALP) staining and alizarin red staining with significantly lowered expressions of the osteogenic marker genes including Alpl, Sp7, Bglap and Ibsp (P<0.01). Transcriptome sequencing verified the reduction of bone mineralization-related gene expressions in Zfp36-deficient cells and indicated the involvement of ERK signaling in the potential regulatory mechanism of Zfp36. Immunoblotting showed that pERK protein expression increased significantly in Zfp36-deficient cells compared with the control cells. In Zfp36-deficient MC3T3-E1 cells, inhibition of activated ERK/MAPK signaling with U0126 resulted in obviously enhanced ALP staining and significantly increased expressions of osteoblast differentiation markers Runx2 and Bglap (P<0.05). Conclusions ZFP36 is involved in the regulation of osteoblast differentiation of mouse BMSCs and preosteoblasts, and ZFP36 deficiency causes inhibition of osteoblast differentiation of the cells by activating the ERK/MAPK signaling pathway.

Objective To observe the change of high mobility group protein B1 (HMGB1) in patients with hepatocellular carcinoma (HCC) before and after transcatheter arterial chemoembolization (TACE) and its effect on prognosis.Methods A total of 68 HCC patients only with TACE treatment were selected as the research objects from June 2012 to June 2014 in Shandong Tumor Hospital.The serum levels of HMGB1 of all the patients were detected 1 day before TACE and 1 month after TACE.The change of HMGB1 expression before and after TACE was analyzed.According to the reference data,the patients were divided into the high-expression group (≥ 17.5 ng/ml) and the low-expression group (＜ 17.5 ng/ml).The short-term efficacy of the two groups of patients and their survival time were compared.Results The pre-operative HMGB1 level of patients was (40.6 + 13.6) ng/ml,and the 1-month postoperative HMGB1 level was (20.1 + 6.9) ng/ml,and the difference was statistically significant (t =4.22,P =0.040).The effective rate in patients with low HMGB1 expression after TACE was 65.00％,and 39.29％ in patients with high HMGB1 expression,with a significant difference (x2 =4.390,P =0.036).The 1,2,and 3 year survival rates of low HMGB1 expression group were 77.50％,50.00％ and 27.50％,respectively,which were significandy higher than high HMGB1 expression group (57.14％,21.43％ and 7.14％),with a significant difference (x2 =8.301,P =0.040).Conclusion TACE can reduce the HMGB1 expression level in serum of patiens with HCC.The patients with low expression of HMGB1 have the better short-term efficacy and the longer survival time.

Objective:To study the actual effect of the use of personal protective equipment of the examined individuals, and provide reference and basis for the correct use of personal protective equipment and the radiological health administrative law enforcement.Methods:From February to June 2022, the imaging department of Qingdao Municipal Hospital selected 170 patients who underwent X-ray imaging examination (oral panoramic, dental radiography, DR photography, CT scanning), including 25 with oral panoramic and dental radiography, 60 with CT scanning and 60 with DR imaging. The thermoluminescent dosimeter was used to detect the ambient dose equivalent at the point of concern for 170 examined individuals who have used personal protective equipment to cover their sensitive parts, and to analyze the data detected at the same point as above when routinely using the same equipment.Results:There was a statistically significant difference in the dose equivalent at the same points inside and outside the lead neckband ( t=-2.23, P<0.05). There was no statistically significant difference in the dose equivalent at the same point inside and outside the lead collar during dental radiography ( P>0.05). During DR photography (chest PA, lateral and lumbar AP), the examined individuals were wearing lead aprons. Among them, there was a statistically significant difference in the dose equivalent at the same points inside and outside the lead aprons of children′s chest PA and adults′ chest PA ( U=10.00, 19.00, P<0.05). There was no statistically significant difference in the dose equivalent at the same points inside and outside the lead aprons of adult′s chest PA and lumbar AP ( P>0.05). When performing CT scan (chest or upper abdomen), there was a statistically significant difference in the dose equivalent at the same points of wrapped lead aprons( U=878.50, 11.00, P<0.05). Conclusions:The correct use of personal protective equipment is a complex technical problem. It is very important to fully and accurately understand the optimization principle of radiation protection and correctly use personal protective equipment for the examined individuals. The administrative punishment of radiation health on the use of personal protective equipment of the examined individuals should be cautious.

ObjectiveTo analyze the characteristics of HIV-1 molecular network and pretreatment drug resistance genes in the middle-aged and elderly people aged ≥50 years in Huzhou City, Zhejiang Province, and to provide an evidence for the prevention and control of AIDS epidemic. MethodsA total of 332 samples from the newly reported and untreated AIDS patients aged ≥50 years in Huzhou City from January 2020 to December 2023 were collected, pol genes were amplified by reverse transcription polymerase chain reaction (RT-PCR) and nested polymerase chain reaction (nest⁃PCR). Phylogenetic trees analyzing the subtypes were constructed, and a molecular network with a gene distance threshold of 1.0% were constructed at the same time. Mutation sites of drug resistance-related genes were identified through the Data Analysis and Detection System of HIV-1 Resistance Gene Detection of Stanford University, USA. ResultsSequence samples of 308 patients were obtained, and9 genotypes were identified, including CRF07_BC in 172 cases (55.8%), CRF01_AE in 61 cases (19.8%), CRF08_BC in 43 cases (14.0%), CRF85_BC in 9 cases (2.9%), and CRF55_01B in 8 cases (2.6%), subtype B in 5 cases (1.6%), subtype C in 4 cases (1.3%), CRF67_01B in3 cases (1.0%), and unique recombination URF01_AE/07_BC in 3 cases (1.0%). When the gene distance threshold was 1.0%, 28 molecular clusters were formed, and 139 cases were connected to the network, with an access rate of 45.0%. The largest transmission cluster C1 contained 44 cases infected with CRF07_BC subtype, all of whom were heterosexually transmitted, and predominantly by males. A total of 30 patients were found to have low-grade or higher drug resistance mutations, and the pretreatment drug resistance rate was 9.7% (30/308). Among them, there were 5 cases (16.7%) of protease inhibitor (PI) related drug resistance mutations, and 26 cases (86.7%) of non-nucleoside reverse transcriptase inhibitors (NNRTI) related drug resistance mutations. ConclusionCRF07_BC is the subtype with the most clusters among the middle-aged and elderly infected patients aged ≥50 years in Huzhou City. Middle-aged and elderly transmission clusters are formed within the three counties of WX, NX and CX through related activities. Molecular network monitoring on newly reported cases aged ≥50 years in Huzhou City should be strengthened so that the new characteristics of epidemic changes can be detected in time, providing a scientific basis for adjusting AIDS prevention and control measures for the elderly.