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Arsenic, a hazardous heavy metal with potent carcinogenic properties, significantly affects key rice-producing regions worldwide. In this study, we present a quantitative trait locus (QTL) mapping investigation designed to identify candidate genes responsible for conferring tolerance to arsenic toxicity in rice (Oryza sativa L.) during the seedling stage. This study identified 17 QTLs on different chromosomes, including qCHC-1 and qCHC-3 on chromosome 1 and 3 related to chlorophyll content and qRFW-12 on chromosome 12 related to root fresh weight. Gene expression analysis revealed eight candidate genes exhibited significant upregulation in the resistant lines, OsGRL1, OsDjB1, OsZIP2, OsMATE12, OsTRX29, OsMADS33, OsABCG29, and OsENODL24. These genes display sequence alignment and phylogenetic tree similarities with other species and engaging in protein-protein interactions with significant proteins. Advanced gene-editing techniques such as CRISPR-Cas9 to precisely target and modify the candidate genes responsible for arsenic tolerance will be explore. This approach may expedite the development of arsenic-resistant rice cultivars, which are essential for ensuring food security in regions affected by arsenic-contaminated soil and water., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The rice blast fungus Magnaporthe oryzae poses a significant challenge to maintaining rice production. Developing rice varieties with resistance to this disease is crucial for its effective control. To understand the genetic variability of blast isolates collected between 2015 and 2017, the 27 monogenic rice lines that carry specific resistance genes were used to evaluate blast disease reactions. Based on criteria such as viability, virulence, and reactions to resistance genes, 20 blast isolates were selected as representative strains. To identify novel resistance genes, a quantitative trait locus analysis was carried out utilizing a mixture of the 20 representative rice blast isolates and a rice population derived from crossing the blast-resistant cultivar 'Cheongcheong' with the blast-susceptible cultivar 'Nagdong'. This analysis revealed a significant locus, RM1227-RM1261 on chromosome 12, that is associated with rice blast resistance. Within this locus, 12 disease resistance-associated protein genes were identified. Among them, OsDRq12 , a member of the nucleotide-binding, leucine-rich repeat disease resistance family, was chosen as the target gene for additional computational investigation. The findings of this study have significant implications for enhancing rice production and ensuring food security by controlling rice blast and developing resistant rice cultivars., Competing Interests: The author(s) declare no conflict of interest.

Due to the emerging global epidemic of obesity, developing safe and effective agents for anti-obesity is urgently needed. Our previous study found that 2-pyrimidinylindole derivative Wd3d exhibited potential anti-obesity activity. Herein, to further optimize the potential moiety, structural modifications were proceeded for two rounds in this study. Firstly, we designed, synthesized, and evaluated 36 new derivatives of 2-pyrimidinylindole scaffold with different substituents on the indole ring and pyrimidine ring to investigate their structure-activity relationship (SAR). Then, analogs with potent activity had the aldehyde group replaced with the acylhydrazone group to reduce cytotoxicity and improve metabolic stability. Detailed SAR studies and animal evaluation experiments led to the discovery of the compound 9ga, which significantly reduced TG accumulation with an EC 50 value of 0.07 μM and showed relatively low cytotoxicity with an IC 50 value of around 24 μM. Oral administration of 9ga effectively prevented the excessive growth of body weight and lessened fat mass as well as liver mass, decreased lipid accumulation in the liver and blood, and improved the heart injury parameter in the diet-induced obesity mouse model significantly better than Wd3d. A mechanism study showed that 9ga regulated the lipid metabolism during early adipogenesis by inhibiting PPARγ pathway. In conclusion, our study further highlights the anti-obesity potential of 2-pyrimidinylindole derivatives in diet-induced obesity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development. In this study, we designed two series of novel derivatives to modify this structural feature. Through a structure-activity relationship study, we elucidated the role of the 8a-aldehyde group in toxicity induction. We identified compound 14d , featuring an 8a- N -acylhydrazone moiety, which exhibited significant lipid-lowering activity and reduced toxicity. Compound 14d shares a similar lipid-lowering mechanism with our lead compound 3 , but demonstrates improved pharmacokinetic properties and safety profile. Both oral and injectable administration of 14d significantly reduced body weight gain and ameliorated metabolic syndrome in diet-induced obese mice. Our findings identify 14d as a promising antiobesity agent and highlight the potential of substituting the aldehyde group with an N -acylhydrazone to enhance drug-like properties.

Chimonobambusapleiacantha , a newly-identified species of the genus Chimonobambusa Makino from southeast Sichuan, China, is meticulously described and illustrated herein. It is morphologically similar to Ch.tuberculata , but differs in having 4-angled internodes, thicker wall to 4.5-8.5 mm, more reclinate and elongated root thorns to 5-8 mm long, culm internodes with three grooves and two longitudinal ridges on the branch-bearing side, persistent culm leaves, densely brown-purple setose at the bottom of culm leaf sheaths together with sheath scar, developed foliage leaf fimbriae, 6-8 on each shoulder, ca. 3-8 mm long, abaxially white pubescent foliage leaf blades. Phenologically, new shoots usually appear in September to October. In the light of these key morphological and phenological characteristics, Ch.pleiacantha was identified as a new species of the genus Ch. Makino which is different from published species of this genus., Competing Interests: The authors have declared that no competing interests exist., (Dan-Dan Zhao, Jin-Jun Yue.)

Objective: To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL)., Methods: The relationship of peripheral blood B cell count with clinical features, laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed., Results: Patients were divided into low B-cell count group (B cell＜0.1×10 9 /L, n =34) and high B-cell count group (B cell≥0.1×10 9 /L, n =33) according to the median B cell count values. Compared with the high B cell count group, the low B cell count group had a higher proportion of patients with Lugano stage III-IV, elevated LDH, elevated β 2 -MG and IPI score 3-5 and increased CRP ( P =0.033, 0.000, 0.023, 0.001, 0.033). The peripheral CD3 + and CD4 + cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group ( P =0.010, 0.017). After initial treatment, overall response rate (ORR) and complete remission (CR) rate in high B cell count group were significantly higher than those in low B cell count group ( P =0.032, 0.013). The median follow-up time of patients was 23(2-77) months, progression-free survival (PFS) and overall survival (OS) of patients in the high B cell count group were significantly better than those in the low B cell count group ( P =0.001, 0.002). Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS ( HR =4.108, P =0.002; HR =8.218, P =0.006). Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS ( HR =3.116, P =0.037)., Conclusion: Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy, which is associated with poor clinical prognosis.

Obesity, a global pandemic posing a growing threat to human health, necessitates the development of effective and safe anti-obesity agents. Our previous studies highlighted the lipid-lowering effects of indolylquinazoline Bouchardatine and its derivatives. In this study, we employed scaffold hopping and simplification strategies to design and synthesize two new series derivatives by modifying the D ring. Extensive discussions have been conducted regarding the structure-activity relationship between lipid-lowering activity and the new compounds. These discussions have resulted in the discovery of 2-pyrimidinylindole derivatives as a promising scaffold for anti-obesity treatment. The new 2-pyrimidinylindole derivatives exhibited comparable lipid-lowering activity to the previously reported indolylquinazoline derivatives, including SYSU-3d and R17, with reduced toxicity. The most potent compound, 5a, demonstrated a larger therapeutic index, improved aqueous solubility and oral bioavailability compared to the previous lead compounds. In vivo evaluation indicated that 5a effectively reduced lipid accumulation in adipose tissue, improved glucose tolerance, and mitigated insulin resistance and liver function damage caused by a high-fat and high-cholesterol diet. Mechanism studies indicated that 5a may regulate lipid metabolism through the modulation of the PPARγ signaling pathway. Overall, our study has identified a highly active compound 5a, and provided the basis for further development of 2-pyrimidinylindole as a promising scaffold for obesity treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Metabolic reprogramming is a crucial hallmark of tumorigenesis. Modulating the reprogrammed energy metabolism is an attractive anticancer therapeutic strategy. We previously found a natural product, bouchardatine , modulated aerobic metabolism and inhibited proliferation in the colorectal cancer cell (CRC). Herein, we designed and synthesized a new series of bouchardatine derivatives to discover more potential modulators. We applied the dual-parametric high-content screening (HCS) to evaluate their AMP-activated protein kinase (AMPK) modulation and CRC proliferation inhibition effect simultaneously. And we found their antiproliferation activities were highly correlated to AMPK activation. Among them, 18a was identified with nanomole-level antiproliferation activities against several CRCs. Interestingly, the evaluation found that 18a selectively upregulated oxidative phosphorylation (OXPHOS) and inhibited proliferation by modulating energy metabolism. Additionally, this compound effectively inhibited the RKO xenograft growth along with AMPK activation. In conclusion, our study identified 18a as a promising candidate for CRC treatment and suggested a novel anti-CRC strategy by AMPK activating and OXPHOS upregulating.

The gelatinization temperature of rice is an important factor in determining the eating and cooking quality, and it affects consumer preference. The alkali digestion value (ADV) is one of the main methods used to test the quality of rice and has a high correlation with the gelatinization temperature. For the development of high-quality rice, it is important to understand the genetic basis of palatability-related traits, and QTL analysis is a statistical method linking phenotypic data and genotype data and is an effective method to explain the genetic basis of variation in complex traits. QTL mapping related to the ADV of brown and milled rice was performed using the 120 Cheongcheong/Nagdong double haploid (CNDH) line. As a result, 12 QTLs related to ADV were detected, and 20 candidate genes were selected from the RM588-RM1163 region of chromosome 6 through screening by gene function analysis. The comparison of the relative expression level of candidate genes showed that OsSS1q6 is highly expressed in CNDH lines with high ADV in both brown rice and milled rice. In addition, OsSS1q6 has high homology with the starch synthase 1 protein and interacts with various starch biosynthesis-related proteins, such as GBSSII, SBE, and APL. Therefore, we suggest that OsSS1q6 identified through QTL mapping could be one of the various genes involved in the gelatinization temperature of rice by regulating starch biosynthesis. This study can be used as basic data for breeding high-quality rice and provides a new genetic resource that can increase the palatability of rice., Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01392-2., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Amino acids are building blocks of proteins that are essential components of a wide range of metabolic pathways in plant species, including rice species. Previous studies only considered changes in the amino acid content of rice under NaCl stress. Here, we evaluated profiles of essential and non-essential amino acids in four rice genotype seedlings in the presence of three types of salts, namely NaCl, CaCl 2 , and MgCl 2 . Amino acid profiles in 14-day-old rice seedlings were determined. The total essential and non-essential amino acid contents in cultivar Cheongcheong were considerably increased upon NaCl and MgCl 2 application, whereas total amino acids were increased upon NaCl, CaCl 2 , and MgCl 2 application in the cultivar Nagdong. The total amino acid content was significantly lower in the salt-sensitive cultivar IR28 and salt-tolerant Pokkali under different salt stress conditions. Glycine was not detected in any of the rice genotypes. We observed that cultivars with the same origin respond similarly to each other under salinity stress conditions: cultivars Cheongcheong and Nagdong were found to show increased total amino acid content, whereas the content in foreign cultivars IR28 and Pokkali was found to decrease. Thus, our findings showed that the amino acid profile of each rice cultivar might depend on the origin, immune level, and genetic makeup of the respective cultivar.

We detected a new target quantitative trait locus (QTL) for lodging resistance in rice by analyzing lodging resistance to typhoons (Maysak and Haishen) using a scale from 0 (no prostrating) to 1 (little prostrating or prostrating) to record the resistance score in a Cheongcheong/Nagdong double haploid rice population. Five quantitative trait loci for lodging resistance to typhoons were detected. Among them, qTyM6 and qTyH6 exhibited crucial effects of locus RM3343-RM20318 on chromosome 6, which overlaps with our previous rice lodging studies for the loci qPSLSA6-2 , qPSLSB6-5 , and qLTI6-2 . Within the target locus RM3343-RM20318, 12 related genes belonging to the cytochrome P450 protein family were screened through annotation. Os06g0599200 ( OsTyM/Hq6 ) was selected for further analysis. We observed that the culm and panicle lengths were positively correlated with lodging resistance to typhoons. However, the yield was negatively correlated with lodging resistance to typhoons. The findings of this study improve an understanding of rice breeding, particularly the culm length, early maturing, and heavy panicle varieties, and the mechanisms by which the plant's architecture can resist natural disasters such as typhoons to ensure food safety. These results also provide the insight that lodging resistance in rice may be associated with major traits such as panicle length, culm length, tiller number, and heading date, and thereby improvements in these traits can increase lodging resistance to typhoons. Moreover, rice breeding should focus on maintaining suitable varieties that can withstand the adverse effects of climate change in the future and provide better food security., Competing Interests: The authors declare no conflict of interest.

Background: Diet acts on the human body through digestion in the stomach and absorption in the intestines. Thus, the emptying of the stomach should be the focus of the research mechanism of the combined medicine and food treatment of diabetes. The emptying function of the stomach and the secretion of related hormones may be the key points of traditional Chinese medicine. In the clinic, Yunvjian is a famous traditional Chinese formula for preventing and curing diabetes. However, the pharmacological action and mechanism of Yunvjian are also need to be probe., Objective: To assess the effect of Yunvjian on glucose, insulin level and gastric emptying function and related hormones on high-fat diet combined with STZ-induced diabetic rats., Methods: High-fat diet combined with STZ was used to construct type 2 diabetes mellitus (T2DM) rats model and received a 4-week Yunvjian administration. The animals were divided into 6 groups, respectively, as the Control group, the DM group, the DM + Acarbose group, the DM + YNH group, and the DM + YNL group. Radionuclide single-photon emission computed tomography (SPECT) technology was used to observe the gastric emptying rate and half-empty time; blood was took to test fasting insulin, and then the insulin resistance index (HOMA-IR) was calculated; HE staining was performed to detect islets and gastric antrum, immunohistochemical staining was performed to detect the number and morphology of pancreatic β cells and gastric antrum Cajal cells, and the average optical density was calculated; the expression of ghrelin hormone in gastric antrum and serum was detected by ELISA and immunofluorescence; the expression of GHRS mRNA in gastric antrum was detected by RT-PCR method., Results: Yunvjian could significantly improve the glucose level and insulin function of rats. Compared with the DM group, Yunvjian was beneficial to low fasting blood glucose (FBG) ( P < 0.01), increased glucose tolerance, and improved islet function at the same time ( P < 0.05). At the same time, compared with the DM group (25.02 ± 0.05, 44 ± 12.33), the emptying rate of the DM + YNH group was significantly faster (64.98 ± 0.12), and the half row time was shortened (26 ± 8.29, P < 0.05). The gastric ghrelin levels in each group of Yunvjian increased with different degrees compared with the DM group (616.2 ± 26.23), especially in the DM + YNH group (863.51 ± 23.76, P < 0.01). Correspondingly, the expression of gastric GHSR mRNA in the DM + YNH and DM + YNL groups increased significantly compared with the DM group ( P < 0.01)., Conclusions: Yunvjian can effectively control glucose and improve islet function, which may be closely related to its influence on gastric emptying function and related hormone secretion regulation., Competing Interests: The authors declare that the research was conducted in the absence of any business or economic relationships that could be suspected of potential conflicts of interest., (Copyright © 2023 Wan-Yu Luo et al.)

This paper aims to explore the neuroprotective effect of cinnamaldehyde(CA) in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced subacute Parkinson's disease(PD) and the mechanism. To be specific, male C57 BL/6 mice(n=72, SPF) were randomized into control group, model group, positive control(madopar 0.1 mg·g~(-1)) group, and low-dose, me-dium-dose, and high-dose CA groups(0.15, 0.30, 0.60 mg·g~(-1)). MPTP(intraperitoneal injection, 0.03 mg·g~(-1), once a day for 5 days) was used to induce subacute PD in mice except for the control group. The administration began from the day of modeling and lasted 19 days. On the 0 th, 12 th, and 19 th day, the open field test, pole test, and rotarod test were carried out. After the tests, the mice were killed and brains were separated. In addition, the organ index was measured. The number of cells in substantia nigra(SN) in the midbrain of MPTP-induced PD model mice was detected based on hematoxylin and eosin(HE) staining. The levels of tyrosine hydroxylase(TH)-and α-synuclein(α-Syn)-positive cells in SN were determined by immunohistochemical staining, and the protein levels of TH and α-Syn in SN by Western blot. The results showed that the MPTP-stimulated mice had abnormal behaviors such as erect hair, arched back, rigidity of the tail, slow movement, and tremor, decreased number of crossings and rearing, increased frequency of urination and defecation, longer time of pole climbing, and shorter time of staying on the rotating rod. In addition, the mice showed obvious damage of neurons in the SN and reduced neuron cells in irregular arrangement with some shrinking. In addition, the average optical density of TH in SN decreased and that of α-Syn increased. All these suggested the successful modeling. CA displayed obvious therapeutic effect on the PD mice, as manifested by the increased number of crossings and rearing, decreased frequency of urination and defecation, shorter time of climbing pole, longer time of staying on the rotating rod, and more neuron cells in the SN with a few pykno-tic cells. Moreover, CA significantly alleviated the decrease of TH and the overexpression of α-Syn in SN. As a result, the MPTP-induced injury of dopaminergic neurons was alleviated. The performance of 0.3 mg·g~(-1) CA was the best. This study is expected to lay a scientific basis for the development of CA products.

The overall effects of gibberellic acid (GA3) with NaCl on different rice genotypes are inadequately understood. The present study determines the effect of different GA3 (50 and 100 µM) concentrations on the morphophysiological, molecular and biochemical effects of 120 mM NaCl salt stress in rice seedlings. Salt stress reduced germination percentages and seedling growth and decreased bioactive GA content. It also downregulated the relative expression of α-amylase-related genes - OsAmy1A , OsAmy1C , and OsAmy3C in the salt-sensitive IR28 cultivar. Salt stress differentially regulated the expression of GA biosynthetic genes. Salt stress increased antioxidant activity in all rice genotypes tested, except in IR28. GA3 mitigates the effect of salt stress, rescuing seed germination and growth attributes. GA3 significantly increased bioactive GA content in Nagdong and pokkali (50 µM) and Cheongcheong and IR28 (100 µM) cultivars. The α-amylase genes were also significantly upregulated by GA3. Similarly, GA3 upregulated OsGA2ox1 and OsGA2ox9 expression in the Cheongcheong and salt-sensitive IR28 cultivars. The present study demonstrated that salt stress inactivates bioactive GA - inhibiting germination and seedlings growth - and decreases bioactive GA content and GSH activity in IR28 and Pokkali cultivars. Further, GA3 significantly reversed the effects of 120 mM NaCl salt stress in different rice genotypes. The current study suggested that the known coastal area salinity concentration can be significantly recovered with the application of exogenous GA3. Thus, it could be possible to grow eco-friendly rice close to the coastal zone in order to reduce the damage caused by salinity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Farooq, Khan, Zhao, Asif, Kim, Jang, Park, Lee and Kim.)

Understanding the changes and influencing factors of soil organic carbon density (SOCD) during the conversion of uncultivated natural soil to croplands is of great significance for the assessment of carbon sequestration in arid areas. In this study, we compared SOCD in the uncultivated soil and that in croplands with different cultivation years (2-5, 12-15, 25-30, 40-50 years) in the Northeastern Ulan Buh Desert. The change of SOCD and its influencing factors at 0-2 m soil depth during the conversion of uncultivated natural soil to croplands were explored by the method of replacing time with space. The results showed that SOCD at the shallow soil depth (0-0.4 m) in croplands increased continuously with cultivation years, but basically at low levels (0.990-1.983 kg·m -2 ). The SOCD at deep soil (1.2-2 m) increased in the croplands with longer cultivation years (25-30 and 40-50 years), whereas no obvious change trends in both the croplands with shorter cultivation years (2-5 and 12-15 years) and the uncultivated natural soil. The SOCD at deep soil (1.2-2 m) were relatively large (28.9%-38.6%) of the 0-2 m soil depth of uncultivated natural soil and croplands with different cultivation years. The vertical distribution of SOCD in croplands with different cultivation years were well fitted by quadratic functions (with R 2 ranging from 0.757 to 0.972). It was noteworthy that soil clay and silt contents had dominant influences on SOCD at all the soil profile (0-2 m), and that cultivation years mainly contributed to the accumulation of SOC at the shallow soil (0-0.4 m).

Background: Approximately half of all new cases of gastric cancer (GC) and related deaths occur in China. More than 80% of patients with GC are diagnosed at an advanced stage, which results in poor prognosis. Although HER2 -directed therapy and immune checkpoint inhibitors have been somewhat successful, new drugs are still needed for the treatment of GC. Notably, several gene fusion-targeted drugs have been approved by the United States Food and Drug Administration for solid tumors, including GC, such as larotrectinib for NTRK fusion-positive cancers and zenocutuzumab for NRG1 fusion-positive cancers. However, gene fusions involving targetable genes have not been well characterized in Chinese patients with GC., Aim: To identify the profile of fusions involving targetable genes in Chinese patients with GC using clinical specimens and determine the distribution of patients with gene fusion variants among the molecular subtypes of GC., Methods: We retrospectively analyzed gene fusion events in tumor tissue samples from 954 Chinese patients with GC. Clinicopathological characteristics were obtained from their medical records. Genetic alterations, such as single nucleotide variants, indels, amplifications, and gene fusions, were identified using a targeted sequencing panel containing 825 genes. Fusions were validated by fluorescence in situ hybridization (FISH) using break-apart probes. The microsatellite instability (MSI) status was evaluated using MSIsensor from the targeted sequencing panel data. Tumor mutational burden (TMB) was calculated using the total number of nonsynonymous mutations divided by the total genomic targeted region. Chi-square analysis was used to determine the enrichment of gene fusions associated with the molecular subtypes of GC., Results: We found that 1.68% (16/954) of patients harbored 20 fusion events involving targetable genes. RARA fusions ( n = 5) were the most common, followed by FGFR2 , BRAF , MET , FGFR3 , RET, ALK, EGFR, NTRK2, and NRG1 fusions. Two of the RARA fusions, EML4-ALK (E6:E20) and EGFR-SEPTIN14 (E7:E10) , have been identified in other tumors but not in GC. Surprisingly, 18 gene fusion events were previously not reported in any cancer types. Twelve of the eighteen novel gene fusions included complete exons encoding functional domains of targetable genes, such as the tyrosine kinase domain of receptor tyrosine kinases and the DNA- and ligand-binding domains of RARA . Consistent with the results of detection using the targeted sequencing fusion panel, the results of FISH (fluorescence in situ hybridization) confirmed the rearrangement of FGFR2 and BRAF in tumors from patients 04 and 09, respectively. Genetic analysis indicated that the fusion genes were significantly enriched in patients with ERBB2 amplification ( P = 0.02); however, there were no significant differences between fusion-positive and fusion-negative patients in age, sex, MSI status, and TMB., Conclusion: We characterized the landscape of fusions involving targetable genes in a Chinese GC cohort and found that 1.68% of patients with GC harbor potential targetable gene fusions, which were enriched in patients with ERBB2 amplification. Gene fusion detection may provide a potential treatment strategy for patients with GC with disease progression following standard therapy., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Low temperature is a serious threat to the seed emergence of rice, which has become one of the main limiting factors affecting rice production in the world. It is of great significance to find the candidate genes controlling low-temperature tolerance during seed germination and study their functions for breeding new rice cultivars with immense low-temperature tolerance during seed germination. In the current experiment, 120 lines of the Cheongcheong Nagdong Double Haploid (CNDH) population were used for quantitative trait locus (QTL) analysis of low-temperature germinability. The results showed a significant difference in germination under low different temperature (LDT) (15 °C, 20 °C) conditions. In total, four QTLs were detected on chromosome 3, 6, and 8. A total of 41 genes were identified from all the four QTLs, among them, 25 genes were selected by gene function annotation and further screened through quantitative real-time polymerase chain reaction (qRT-PCR). Based on gene function annotation and level of expression under low-temperature, our study suggested the OsGPq3 gene as a candidate gene controlling viviparous germination, ABA and GA signaling under low-temperature. This study will provide a theoretical basis for marker-assisted breeding and lay the basis for further mining molecular mechanisms of low-temperature germination tolerance in rice.

Climate change leads to soil salinization, and the dynamic scarcity of freshwater has negatively affected crop production worldwide, especially Oryza sativa . The association among ion uptake, gene expression, antioxidant, biomass, and root and shoot development under different salt stress are not fully understood. Many studies are related to the effect of NaCl only. This study used two salts (CaCl 2 and MgCl 2 ) along with NaCl and analyzed their effects on mineral uptake (macronutrients and micronutrients), gene expression, seed germination, antioxidants, plant growth, and biomass in different rice genotypes. CaCl 2 (up to 200 mM) slightly increased the germination percentage and seedling growth, whereas, 150 mM MgCl 2 in the soil increased the root, shoot length, and fresh and dry weight in cultivars IR 28 and Cheongcheong. All agronomic traits among rice genotypes were drastically reduced by NaCl stress compared to other salts. Different salt stress differentially regulated ion uptake in the roots and shoots among different rice genotypes. Under different salt stress, a consistent decrease in Ca 2+ , Mn 2+ , and Fe 2+ ions was observed in the roots of Cheongcheong, Nagdong, and IR 28. Similarly, under different salts, the stress in the shoots of Cheongcheong (Ca 2+ , Na + , and Zn 2+ ) and Nagdong (Ca 2+ , Mg 2+ , Na + , and Zn 2+ ) and the shoots of IR 28 (Ca 2+ and Mg 2+ ) consistently increased. Under different salts, a salt stress-related gene was expressed differentially in the roots of rice genotypes. However, after 6 and 12 h, there was consistent OsHKT1 , OsNHX1 , and OsSOS1 gene upregulation in the shoots of Nagdong and roots and shoots of the salt-tolerant cultivar Pokkali. Under different salt stress, glutathione (GSH) content increased in the shoot of IR 28 and Nagdong by NaCl, and MgCl 2 salt, whereas, POD activity increased significantly by CaCl 2 and MgCl 2 in cultivar Cheongcheong and IR 28 shoot. Therefore, this study suggested that Pokkali responded well to NaCl stress only, whereas, the plant molecular breeding lab cultivar Nagdong showed more salt tolerance to different salts (NaCl, CaCl 2 , and MgCl 2 ). This can potentially be used by agriculturists to develop the new salt-tolerant cultivar "Nagdong"-like Pokkali., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Farooq, Asif, Jang, Park, Zhao, Kim and Kim.)

An ideal plant architecture is an important condition to achieve high crop yields. The tiller angle is an important and complex polygenic trait of rice ( Oryza sativa L.) plant architecture. Therefore, the discovery and identification of tiller angle-related genes can aid in the improvement of crop architecture and yield. In the present study, 222 SSR markers were used to establish a high-density genetic map of rice doubled haploid population, and a total of 8 quantitative trait loci (QTLs) were detected based on the phenotypic data of the tiller angle and tiller crown width over 2 years. Among them, four QTLs ( qTA9 , qCW9 , qTA9-1 , and qCW9-1 ) were overlapped at marker interval RM6235-RM24288 on chromosome 9 with a large effect value regarded as a stable major QTL. The selected promising related genes were further identified by relative gene expression analysis, which gives us a basis for the future cloning of these genes. Finally, OsSAURq9 , which belongs to the SMALL AUXIN UP RNA ( SAUR ), an auxin-responsive protein family, was selected as a target gene. Overall, this work will help broaden our knowledge of the genetic control of tiller angle and tiller crown width, and this study provides both a good theoretical basis and a new genetic resource for the breeding of ideal-type rice.

Background and Purpose: Non-alcoholic steatohepatitis (NASH) is the more severe form of metabolic associated fatty liver disease (MAFLD) and no pharmacological treatment as yet been approved. Identification of novel therapeutic targets and their agents is critical to overcome the current inadequacy of drug treatment for NASH., Experimental Approach: The correlation between heat shock factor 1 (HSF1) levels and the development of NASH and the target genes of HSF1 in hepatocyte were investigated by chromatin-immunoprecipitation sequencing. The effects and mechanisms of SYSU-3d in alleviating NASH were examined in relevant cell models and mouse models (the Ob/Ob mice, high-fat and high-cholesterol diet and the methionine-choline deficient diet-fed mice). The actions of SYSU-3d in vivo were evaluated., Key Results: HSF1 is progressively reduced with mitochondrial dysfunction in NASH pathogenesis and activation of this transcription factor by its newly identified activator SYSU-3d effectively inhibited all manifestations of NASH in mice. When activated, the phosphorylated HSF1 (Ser326) translocated to nucleus and bound to the promoter of PPARγ coactivator-1α (PGC-1α) to induce mitochondrial biogenesis. Thus, increasing mitochondrial adaptive oxidation and inhibiting oxidative stress. The deletion of HSF1 and PGC-1α or recovery of HSF1 in HSF1-deficiency cells showed the HSF1/PGC-1α pathway was mainly responsible for the anti-NASH effects of SYSU-3d independent of AMP-activated protein kinase (AMPK)., Conclusion and Implications: Activation of HSF1 is a practical therapeutic approach for NASH treatment via the HSF1/PGC-1α/mitochondrial pathway and SYSU-3d can be considered as a potential candidate for the treatment of NASH., (© 2021 The British Pharmacological Society.)

Rice tillers are one of the most important traits for the yield and development of rice, although little is known about its mode of inheritance. Tiller numbers were recorded every 7 days a total of nine times, starting 30 days after transplantation. Quantitative trait locus (QTL) based analysis on a set of double haploid population derivatives of a cross between the Cheongcheong and Nagdong varieties identified a major effect of locus RM18130-RM3381 on chromosome 5, which was expressed in eight different growth stages. Within the target region RM18130-RM3381 (physical distance: 2.08 Mb), 61 candidate genes were screened by annotation. Among the candidate genes, Os05g0230700 (named OsIAA17q5 ), which belongs to the family of auxin-responsive genes, was selected as a target. Auxin promotes cell division and meristem maintenance and is an effective plant regulator which influences plant growth and development by altering the expression of various genes. OsIAA17q5 is expected to control the number of tillers. The present study provides further understanding of the basic genetic mechanisms that selectively express the control of tiller numbers in different growth stages, as well as provides valuable information for future research aimed at cloning the target gene. These results may contribute to developing a comprehensive understanding of the basic genetic processes regulating the developmental behavior of tiller numbers in rice.

The indolyl-4(3 H )-quinazolinone core is an important structural motif in functional molecules. However, few methods exist for its direct modification, which limits its potential application. Reported herein is a palladium-mediated amination of halogen-containing indolyl-4(3 H )-quinazolinones with a variety of primary and secondary amines via the corresponding palladium oxidative addition complexes. The protocol allows the facile synthesis of indolyl-4(3 H )-quinazolinone derivatives with amino groups at all the positions of the benzene ring in moderate to good yields with mild reaction conditions and good functional group tolerance. Furthermore, the antitumor activity of these products was evaluated.

Cardiovascular safety assessment is vital for drug development, yet human cardiovascular cell models are lacking. In vitro mass-generated human pluripotent stem cell (hPSC)-derived cardiovascular cells are a suitable cell model for preclinical cardiovascular safety evaluations. In this study, we established a preclinical toxicology model using same-origin hPSC-differentiated cardiomyocytes (hPSC-CMs) and endothelial cells (hPSC-ECs). For validation of this cell model, alirocumab, a human antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), was selected as an emerging safe lipid-lowering drug; atorvastatin, a common statin (the most effective type of lipid-lowering drug), was used as a drug with reported side effects at high concentrations, while doxorubicin was chosen as a positive cardiotoxic drug. The cytotoxicity of these drugs was assessed using CCK8, ATP, and lactate dehydrogenase release assays at 24, 48, and 72 h. The influences of these drugs on cardiomyocyte electrophysiology were detected using the patch-clamp technique, while their effects on endothelial function were determined by tube formation and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake assays. We showed that alirocumab did not affect the cell viability or cardiomyocyte electrophysiology in agreement with the clinical results. Atorvastatin (5-50 μM) dose-dependently decreased cardiovascular cell viability over time, and at a high concentration (50 μM, ~100 times the normal peak serum concentration in clinic), it affected the action potentials of hPSC-CMs and damaged tube formation and Dil-Ac-LDL uptake of hPSC-ECs. The results demonstrate that the established same-origin hPSC-derived cardiovascular cell model can be used to evaluate lipid-lowering drug safety in cardiovascular cells and allow highly accurate preclinical assessment of potential drugs., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Background: Tingli Dazao Xiefei decoction (TDXD) has been shown to have a therapeutic effect on heart failure (HF). Nevertheless, its molecular mechanism for treating HF is still unclear., Materials and Methods: TDXD and HF targets were collected from the databases, and protein-protein interaction (PPI) analysis and enrichment analysis were performed on the overlapping targets. Then, AutoDock was employed for molecular docking. Finally, we used the left anterior descending coronary artery (LAD) ligation to induce HF model rats for in vivo experiments and verified the effect and mechanism of TDXD on HF., Results: Network pharmacological analysis showed that the main active components of TDXD in treating HF were quercetin, kaempferol, beta-carotene, isorhamnetin, and beta-sitosterol, and the core targets were IL-6, VEGFA, TNF, AKT1, and MAPK1. Multiple gene functions and signaling pathways were obtained by enrichment analysis, among which inflammation-related, PI3K/Akt, and MAPK signaling pathways were closely related to HF. Furthermore, the molecular docking results showed that the core targets had good binding ability with the main active components. Animal experiments showed that TDXD could effectively improve left ventricular ejection fraction (EF) and left ventricular fractional shortening (FS), decrease left ventricular internal diastolic diameter (LVIDd) and left ventricular internal systolic diameter (LVIDs), reduce the area of myocardial fibrosis, and decrease serum BNP, LDH, CK-MB, IL-6, IL-1 β , and TNF- α levels in HF rats. Meanwhile, TDXD could upregulate the expression of Bcl-2, downregulate the expression of Bax, and reduce cardiomyocyte apoptosis. At the same time, it was verified that TDXD could significantly decrease the expression of PI3K, P-Akt, and P-MAPK. Captopril showed similar effects., Conclusions: Combining network pharmacological analysis and experimental validation, this study verified that TDXD could improve cardiac function and protect against cardiac injury by inhibiting the activation of PI3K/Akt and MAPK signaling pathways., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this study., (Copyright © 2021 Dan-Dan Zhao et al.)

A vaccine against Trichinella spiralis infection is urgently needed to interrupt its transmission from domestic animals to humans. However, no vaccine against T. spiralis is currently available. Our previous study demonstrated that the use of the 43-kDa glycoprotein present in excretory-secretory (ES) proteins of muscle larvae (ML) as an intramuscular DNA vaccine led to a 52.1% protection rate against T. spiralis infection. Attenuated Salmonella strains have the advantage of eliciting mucosal immunity, which is important for controlling T. spiralis infections at the intestinal stage and can be provided as vaccines via oral or intranasal routes. Therefore, in this study, complete 43-kDa glycoprotein (Ts43) sequences of T. spiralis were cloned into the vector pYA3681, and the recombinant plasmid pYA3681-Ts43 was transformed into the attenuated Salmonella typhimurium strain χ11802. The results showed that oral vaccination of mice with attenuated Salmonella carrying the recombinant plasmid pYA3681-Ts43 induced an evident elevation of the local intestinal mucosal sIgA and serum IgG antibody responses. The flow cytometry results showed that the percentages of CD4 + T cells and secreted IFN-γ, IL-4, and IL-17A in CD4 + T cells were significantly increased in the spleen and mesenteric lymph node (MLN) lymphocytes of the vaccinated groups. In addition, increased levels of the IFN-γ, IL-4, and IL-17A cytokines were also observed in the serum of the immunized groups. The above immune response results in the immunized groups demonstrated that protective immunity was elicited in this study. Finally, vaccinated mice demonstrated a significant 45.9% reduction in ML burden after infection with T. spiralis. This study demonstrated that oral vaccination with Ts43 delivered by attenuated Salmonella elicited local and systemic concurrent Th1/Th2/Th17 immune responses and provided partial protection against T. spiralis infection in BALB/c mice. This is a prospective strategy for the prevention and control of trichinellosis., (Copyright © 2021. Published by Elsevier B.V.)

Zinc finger and BTB domain containing 1(Zbtb1) is a transcriptional suppressor protein, and a member of the mammalian Zbtb gene family. Previous studies have shown that Zbtb1 is essential for T-cell development. However, the role of Zbtb1 in T-cell lymphoma is undetermined. In this study, an EL4 cell line with Zbtb1 deletion was constructed using the CRISPR-Cas9 technique. The expression profiles of microRNA and circRNA produced by the control and gene deletion groups were determined by RNA-seq. In general, 24 differentially expressed microRNA and 16 differentially expressed circRNA were found between normal group and gene deletion group. Through further analysis of differentially expressed genes, GO term histogram and KEGG scatter plot were drawn, and three pairs of miRNA and circRNA regulatory relationships were found. This study describes the differentially expressed microRNA and circRNA in normal and Zbtb1-deficient EL4 cell lines, thus providing potential targets for drug development and clinical treatment of T-cell lymphoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Shi, Lu, Zeng, Cheng, Wang, Sun, Jiang, Yang, Zhao, Huang, Ye, Cao, Yang and Wang.)

Internode length and stem diameter are the primary traits affecting the lodging resistance of rice. Traits related to the length of the panicle (LP), uppermost internode (LUI), second internode (LSI), third internode (LTI), fourth internode (LFI), lowest internode (LLI) as well as stem diameter at the uppermost internode (SDUI), second internode (SDSI), third internode (SDTI), fourth internode (SDFI), and lowest internode (SDLI) in 120 Cheongcheong/Nagdong doubled haploid population were investigated using a quantitative trait locus (QTL) analysis. Thirty-four QTL regions affected LP and the length of each internode. Twenty-six QTL regions were associated with the stem diameter of each internode. RM12285-RM212 on chromosome 1 contained 10 QTLs related to the internode length, which have overlapped for over 2 years. Twenty-three candidate genes were screened using mark interval. Among the candidate genes, Os01g0803900 , named OsCYPq1 , which is in the Cytochrome P450 family , might be involved in gibberellins (GA) synthesis. GA is an essential plant growth regulator that affects plant height. OsCYPq1 catalyzes oxidation steps in the middle part of the GA pathway. OsCYPq1 is expected to provide valuable information to improve the marker assessment for target traits and QTL gene cloning in rice.

Salmonellosis is a worldwide zoonotic disease that poses a serious threat to the reproduction of livestock and poultry and the health of young animals. Probiotics including Bacillus species, have received increasing attention as a substitute for antibiotics. In this study, chicks infected with Salmonella were fed feed supplemented with the BSH to observe the pathological changes in the liver, detect the number of viable bacteria in the liver and spleen, and record the death of the chicks. The results showed that BSH could reduce the pathological changes in the liver and the invasion of Salmonella into the liver and spleen of chicks. In addition, the survival rate of chicks in the BSH experimental group was 60%, while that in the infected control group was 26%, indicating that BSH had a protective effect on chicks infected with Salmonella. Finally, the fecal microflora of 9-day-old chicks was analyzed by 16S rRNA high-throughput sequencing. The results showed that Salmonella infection could cause intestinal flora changes, while BSH could alleviate this change. In addition, BSH also promoted the proliferation of Lactobacillus salivarius in the cecum of chick. This study emphasized that BSH has anti- Salmonella infection effects in chickens and can be used as a candidate microecological preparation strain., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To observe the effect of electroacupuncture (EA) on Cathepsin-B in the synovium of the knee joint of acute gouty arthritis(AGA) rats, so as to explore the mechanism of EA in the treatment of AGA., Methods: A total of 60 male Wistar rats were randomly divided into normal control,model, medication and EA groups, with 15 rats in each group. Rat model of AGA was established by injection of 0.2 mL sodium urate crystal suspension into the left knee joint cavity. The rats in the medication group were treated with colchicine by gavage(0.3 mg·kg -1 ·d -1 ), and the rats in the EA group were treated with EA at the left "Sanyinjiao" (SP6) and "Zusanli"(ST36) for 10 min each time, once a day for a week. The Coderre gait grading standard was used to score the gait of rats. The pathological morphology of synovial tissue of the left knee joint was observed by H.E. staining. The expression levels of Cathepsin-B protein and Nod-like receptor pyrin domain 3(NLRP3), apoptosis-associated speck-like protein containing CARD (ASC),Caspase-1, interleukin-1β(IL-1β) and IL-18 mRNAs were detected by Western blot and real-time fluorescence quantitative PCR, respectively., Results: Compared with the normal control group, the degree of synovitis infiltration in the model group was more serious. And the gait score，the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3,ASC,Caspase-1, IL-1β,IL-18 were significantly increased ( P <0.01).After the interventions, the degree of inflammatory infiltration was mild, The gait score, the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3 and ASC,Caspase-1，IL-1β,IL-18 were significantly decreased in both medication and EA groups in contrast to the model group ( P <0.01, P <0.05). Compared with medication group, the mRNA expression levels of Caspase-1 and IL-18 in the EA group were increased ( P <0.05)., Conclusion: EA may inhibit the activation of NLRP3 inflammasome by reducing the activity of Cathepsin-B in the synovium of the knee joint, so as to treat AGA.

Lactic acid bacteria (LAB) are the primary genera of the intestinal flora and have many probiotic functions. In the present study, Lactobacillus rhamnosus GG (LGG) ATCC 53103 was used to treat BALB/c mice. After LGG intervention, both low and high LGG doses were shown to improve the observed OTU, Chao1, ACE, and Shannon indices, while the Simpson index decreased, demonstrating that LGG can promote intestinal microbiota abundance and diversity. Furthermore, LGG treatment increased the abundances of intestinal Firmicutes , Bacteroides and Actinomycetes while reducing that of Proteobacteria . In addition to its effect on gut the microbiota, LGG could also regulate the host immune system. In the present study, we showed that LGG could affect the percentage of CD3 + T lymphocytes in the spleens (SPLs), mesenteric lymph nodes (MLNs), Peyer's patches (PPs) and lamina propria lymphocytes (LPLs) of mice, including total CD3 + T, CD3 + CD4 + T, and CD3 + CD8 + T lymphocytes. Furthermore, LGG could effectively increase the expression of Th1-type cytokines (IFN-γ) and Th2 cytokines (IL-4) in CD4 + T cells, indicating that the proportion of Th1 and Th2 cells in mice with LGG treatment was in a high equilibrium state compared to the control group. In addition, the IFN-γ/IL-4 ratio was greater than 1 in mice with LGG intervention, suggesting that LGG tends to mediate the Th1 immune response. The results of the present study also showed that LGG upregulated the expression of IL-17 in CD4 + T cells and regulated the percentage of CD4 + CD25 + Foxp3 + Treg cells in various secondary immunological organs, indicating that LGG may promote the balance of Th-17 and Treg cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Shi, Cheng, Yang, Lu, Yin, Zeng, Wang, Jiang, Yang, Wang, Zhao, Huang, Ye, Cao, Yang and Wang.)

Aim: To identify metastatic genes and miRNAs and to investigate the metastatic mechanism of uveal melanoma (UVM)., Methods: GSE27831, GSE39717, and GSE73652 gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database, and the limma R package was used to identify differentially expressed genes (DEGs). Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the DAVID online tool. A comprehensive list of interacting DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. The Cytoscape MCODE plug-in was used to identify clustered sub-networks and modules of hub genes from the protein-protein interaction network. GEPIA online software was used for survival analysis of UVM patients ( n =80) from the The Cancer Genome Atlas (TCGA) cohort. OncomiR online software was used to find that the miRNAs were associated with UVM prognosis from the TCGA cohort. TargetScan Human 7.2 software was then used to identify the miRNAs targeting the genes., Results: There were 1600 up-regulated genes and 1399 down-regulated genes. The up-regulated genes were mainly involved in protein translation in the cytosol, whereas the down-regulated genes were correlated with extracellular matrix organization and cell adhesion in the extracellular space. Among the 2999 DEGs, five genes, Znf391 , Mrps11 , Htra3 , Sulf2 , and Smarcd3 were potential predictors of UVM prognosis. Otherwise, three miRNAs, hsa-miR-509-3-5p, hsa-miR-513a-5p, and hsa-miR-1269a were associated with UVM prognosis., Conclusion: After analyzing the metastasis-related enriched terms and signaling pathways, the up-regulated DEGs are mainly involved in protein synthesis and cell proliferation by ribosome and mitogen-activated protein kinase (MAPK) pathways. However, the down-regulated DEGs are mainly involved in processes that reduced cell-cell adhesion and promoted cell migration in the extracellular matrix through PI3K-Akt signaling pathway, focal adhesion, and extracellular matrix-receptor interactions. Bioinformatics and interaction analysis may provide new insights on the events leading up to the development and progression of UVM., (International Journal of Ophthalmology Press.)

Background: Escherichia coli are mostly commensals but also contain pathogenic lineages. It is largely unclear whether the commensal E. coli as the potential origins of pathogenic lineages may consist of monophyletic or polyphyletic populations, elucidation of which is expected to lead to novel insights into the associations of E. coli diversity with human health and diseases., Methods: Using genomic sequencing and pulsed field gel electrophoresis (PFGE) techniques, we analyzed E. coli from the intestinal microbiota of three groups of healthy individuals, including preschool children, university students, and seniors of a longevity village, as well as colorectal cancer (CRC) patients, to probe the commensal E. coli populations for their diversity., Results: We delineated the 2280 fresh E. coli isolates from 185 subjects into distinct genome types (genotypes) by PFGE. The genomic diversity of the sampled E. coli populations was so high that a given subject may have multiple genotypes of E. coli, with the general diversity within a host going up from preschool children through university students to seniors. Compared to the healthy subjects, the CRC patients had the lowest diversity level among their E. coli isolates. Notably, E. coli isolates from CRC patients could suppress the growth of E. coli bacteria isolated from healthy controls under nutrient-limited culture conditions., Conclusions: The coexistence of multiple E. coli lineages in a host may help create and maintain a microbial environment that is beneficial to the host. As such, the low diversity of E. coli bacteria may be associated with unhealthy microenvironment in the intestine and hence facilitate the pathogenesis of diseases such as CRC.

This study sought to find more exon mutation sites and lncRNA candidates associated with type 2 diabetes mellitus (T2DM) patients with obesity (O-T2DM). We used O-T2DM patients and healthy individuals to detect mutations in their peripheral blood by whole-exon sequencing. And changes in lncRNA expression caused by mutation sites were studied at the RNA level. Then, we performed GO analysis and KEGG pathway analysis. We found a total of 277 377 mutation sites between O-T2DM and healthy individuals. Then, we performed a DNA-RNA joint analysis. Based on the screening of harmful sites, 30 mutant genes shared in O-T2DM patients were screened. At the RNA level, mutations of 106 differentially expressed genes were displayed. Finally, a consensus mutation site and differential expression consensus gene screening were performed. In the current study, the results revealed significant differences in exon sites in peripheral blood between O-T2DM and healthy individuals, which may play an important role in the pathogenesis of O-T2DM by affecting the expression of the corresponding lncRNA. This study provides clues to the molecular mechanisms of metabolic disorders in O-T2DM patients at the DNA and RNA levels, as well as biomarkers of the risk of these disorders., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The class II trans-activator (CIITA) is the master regulator of the major histocompatibility complex (MHC) gene expression. CIITA mutations have been previously associated with several kinds of tumors, while the role of CIITA polymorphisms (rs3087456) in laryngeal squamous cell carcinoma (LSCC) is little known. We evaluate the link between CIITA polymorphisms and the existence of LSCC in patients. This study was conducted with 200 Chinese Han patients (LSCC) and 200 healthy control subjects. The association of CIITA genetic polymorphism rs3087456 with the risk of LSCC was assessed through pyrosequencing. The CIITA expression in LSCC tumor tissue and adjacent normal tissue was detected by immunohistochemistry (IHC) staining. The relationship between the genotype of rs3087456 in controls and in clinical pathology features in LSCC were analyzed, and in-silico analysis was also used for the CIITA gene. The in-silico analysis results showed that the CIITA gene is closely related to genes such as RFX5 and RFXAP. The IHC results showed that CIITA was highly expressed in LSCC tumor tissues, compared with the corresponding adjacent normal tissues. The AG, AG + AA, and A genotypes of rs3087456 of CIITA gene notably increased the risk of LSCC compared to the controls. Our study suggests that CIITA polymorphism (rs3087456) is associated with a higher risk of developing LSCC in a Chinese cohort., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

A new potassium dysprosium polyborate, K 3 DyB 6 O 12 , has been prepared via the high-temperature molten salt method and structurally characterized by single-crystal X-ray diffraction analysis. The structure can be described as a three-dimensional framework composed of isolated bicyclic [B 5 O 10 ] 5- groups and Dy 3+ and K + ions. The Fourier transform IR (FT-IR) and ultraviolet-visible (UV-Vis) spectra were investigated. A series of K 3 Gd 1-x Dy x B 6 O 12 phosphors was prepared and their photoluminescence properties were studied. The K 3 Gd 1-x Dy x B 6 O 12 phosphors exhibit a strong yellow emission band at 577 nm (the 4 F 9/2 → 6 H 13/2 transition of Dy 3+ ) under UV excitation of 275 nm (the 8 S 7/2 → 6 I J transition of Gd 3+ ), suggesting the occurrence of the energy transfer Gd 3+ →Dy 3+ . The optimized doping concentration of the Dy 3+ ion was 8 mol%. We may expect that K 3 Gd 1-x Dy x B 6 O 12 is a promising pale-yellow emission phosphor for visual displays or solid-state lighting.

Objective: To investigate apoptotic effects of berberine, a significant alkaloids component existing in Rhizoma coptidis, and its possible acting mechanism in insulinoma cells., Methods: Different concentrations of berberine were used to treat mouse insulinoma (MIN6) cells for various period of time. The viability and apoptosis of the cells were analyzed using methylthiazolyldiphenvl-tetrazolium bromide assay, flow cytometry and enzyme-linked immuno sorbent assay. Changes in the relating pro- and anti-apoptosis proteins were detected by western-blotting., Results: The half-maximal inhibitory concentration (IC 50 ) of berberine was 5.7 μmol/L on MIN6 cells viability for 16 h. Berberine caused a 20% reduction (P<0.05) in cell number after only 4-h incubation; which reached 50% after 24 h (P<0.01). Berberine treatment for 16 h significantly increased the level of DNA fragmentation. The flow cytometry showed the apoptotic rate increased 2.9- and 4.6-fold after treating with berberine (5 μmol/L) for 8 and 16 h, while 3- and 8.7-fold after 10 μmol/L treatment for 8 and 16 h (P<0.01). Berberine treatment dramatically elevated the expression ratio of Bax to Bcl-2. Meanwhile, berberine notably increased the apoptosis-inducing factors and cytochrome C transforming from the mitochondria to the cytoplasm. Apoptotic protease-activating factor 1 (Apaf-1) was subsequently activated after cytochrome C release. Furthermore, caspase-3 and poly adenosine diphosphate-ribose polymerase were also activated to trigger apoptosis cascade., Conclusion: High concentration (5 and 10 μmol/L) of berberine could induce the apoptosis of MIN6 cells through cytochrome C/Apaf-1/caspase-3 and apoptosis inducing factor (AIF) pathway.

Objective: To investigate the effect of electroacupuncture (EA) on muscular atrophy and expression of microRNAs (Mir-1, Mir-133a, Mir-133b) and some proliferation-related factors of muscle satellite cells as histone deacetylase4 (HDAC4) and the paired box transcription factor Pax7 (Pax7) in skeletal muscle atrophy rats., Methods: Twenty-four male SD rats were randomly and equally divided into sham operation, model and EA groups. The skeletal muscle atrophy model was established by transection of the right sciatic nerve. EA (2 Hz, 1 mA) was applied to the right "Zusanli"(ST36) and "Huantiao"(GB30) for 10 min, once a day, seven times a week for 2 weeks. The wet weight of bilateral gastrocnemius muscles was measured to calculate the ratio of weight between the affected gastrocnemius muscle and healthy gastrocnemius muscle. The cross-sectional area (CSA) of the gastrocnemius muscle on the affected side was measured after H.E. staining. The expression levels of Mir-1, Mir-133a, Mir-133b, HDAC4 mRNA and Pax7 mRNA in the gastrocnemius muscle tissue were detected using quantitative real time-PCR., Results: Compared with the sham operation group, the ratio of wet weight and CSA of the gastrocnemius muscle, and the expression levels of Mir-1 and Mir-133a were significantly decreased in the model group ( P <0.01, P <0.05), while the expression levels of HDAC4 mRNA and Mir-133b significantly up-regulated in the model group ( P <0.05). Following EA intervention, the decreased levels of the ratio of wet weight and CSA of the gastrocnemius muscle were significantly suppressed ( P <0.01), suggesting an inhibition of the skeletal muscle atrophy, and the expression levels of Pax7 and HDAC4 mRNAs were notably up-regulated ( P <0.05), and those of Mir-1, Mir-133a and Mir-133b were significantly or further significantly down-regulated relevant to the model group ( P <0.05)., Conclusion: EA intervention can delay muscular atrophy in rats with denervated gastrocnemius muscle, which may be related with its function in up-regulating the expression of Pax7 and HDAC4 mRNAs and down-regulating the expression of Mir-1, Mir-133a and Mir-133b.

Objective: To observe the effect of electroacupuncture (EA) combined with transplantation of Schwann cells (SCs) on limb locomotor, myelin sheath repair and expression of CD4 and CD8 in compressed spinal cord injury (CSCI) rats, so as to explore its mechanisms underlying improvement of CSCI., Methods: A total of 45 female SD rats were randomly divided into normal control, model, EA, Schwann cell (SC) transplantation, and EA＋SC transplantation groups ( n ＝9 rats in each group). The CSCI model was established by laminectomy at T12-L2 and clip compression. Rats of the SC transplantation group accepted injection of the cultured SC suspension (2×10 6 /6 µL) into the central, upper and lower sites of the injured spinal cord (5 mm in depth) 7-8 days after CSCI modeling. EA (2 Hz) was applied to bilateral "Zusanli" (ST36) and "Sanyinjiao" (SP6) for 10 min, once daily and 6 days a week for 3 weeks. The Basso, Beattie and Bresnahan locomotor rating scale (BBB scale) was used to evaluate the function state of CSCI. Morphological changes of the regional injured tissue were observed under light microscope after H．E. staining. The myelin sheath repair state and survival of SCs were detected by Luxol fast blue (LFB) staining and immunofluorescence histochemistry, and the expression of CD4, CD8 and P0 of the injured spinal cord was detected by Western blot., Results: Compared with the normal control group, the BBB scores at the time-points of 0 d, and 1, 2, and 3 weeks were significantly decreased in the model group ( P <0.001), and those of the EA＋SC transplantation group at the 2 nd and 3 rd week were significantly higher than those of the model group ( P <0.05). No significant changes of BBB scores were found after EA and SC transplantation relevant to the model group ( P >0.05). LFB staining showed a disordered arrangement of the nerve fibers in the white matter, myelinociasis and obvious decrease of the medullated fibers in the model group, and these situations were relatively milder in both EA and SC transplantation groups and obviously milder in the EA＋SC transplantation group. H．E. staining displayed that the structure of the injured region of the spinal cord was incomplete, accompanied with a large number of defect cavities and neuronal karyopyknosis in the model group, while the structure was relatively clear, with an increase of the normal neurons and fewer neuronal karyopyknosis in the EA＋SC transplantation group. Compared with the normal control group, MBP in the model group was significantly decreased ( P <0.001)，and P0 was significantly increased ( P <0.001). Compared with the model group, the expressions of MBP and P0 were significantly increased in the EA, SC transplantation, and EA＋SC transplantation groups ( P <0.01, P <0.001), and was significantly higher in the EA＋SC transplantation group than in both EA and SC transplantation groups ( P <0.001). The average immunofluorescence intensity of Hoechst33342-labeled SCs was significantly higher in the EA＋SC transplantation group than in the SC transplantation group ( P <0.05). After CSCI, the expression levels of spinal CD4, CD8 and P0 proteins had no significant changes in comparison with the normal control group ( P >0.05), while after the intervention and in comparison with the model group, the expression levels of P0 protein were significantly increased in the EA, SC transplantation and EA＋SC transplantation groups ( P <0.05), and was significantly higher in the EA＋SC transplantation group than in both EA and SC transplantation groups ( P <0.05). The expression levels of CD4 and CD8 proteins were significantly lower in the EA＋SC transplantation group than in the SC transplantation group ( P <0.05)．., Conclusion: EA＋SCs transplantation can improve the locomotor function in CSCI rats, which may be related to its effects in increasing the survival of transplanted SCs to promote the remyelination and in reducing the immune rejecting reaction.

Objective: To investigate the therapeutic effects of massage on denervated skeletal muscle atrophy in rats and its mechanism., Methods: Forty-eight male SD rats were randomly divided into model group (n=24) and massage group (n=24). Gastrocnemius muscle atrophy model was established by transecting the right tibial nerve of rat. On the second day after operation, the gastrocnemius muscle of the rats in the massage group was given manual intervention and the model group was not intervened. Six rats were sacrificed at the four time points of 0 d, 7 d, 14 d and 21 d. The gastrocnemius of the rats were obtained and measured the wet mass ratio after weighing. Cross-sectional area and diameter of the muscle fiber were measured after HE staining. The relative expressions of miR-23a, Akt, MuRF1 and MAFbx mRNA were tested with qPCR., Results: Compared with 0 d, the wet weight ratio, cross-sectional area and diameter of gastrocnemius muscle showed a progressive decline in the model group and massage group. The wet weight ratio, cross-sectional area and diameter of gastrocnemius muscle in the massage group were higher than those in the model group on 7 d, 14 d and 21 d (P＜0.05, P＜0.01). Compared with 0 d, the expressions of MuRF1, MAFbx and Akt mRNA were increased first and then were decreased in the model group and massage group. The expression of MuRF1 mRNA in massage group was lower than that in model group on 7 d and 21 d (P＜0.05, P＜0.01). The expression of MAFbx mRNA in massage group was lower than that in model group on 7 d, 14 d and 21 d (P＜0.01, P＜0.05, P＜0.01). The expression of Akt mRNA in massage group was higher than that in model group on 7 d, 14 d and 21 d (P＜0.05, P＜0.01). Compared with 0 d, the expression of miR-23a mRNA was increased in the model group and massage group on 21 d, and the expression of miR-23a mRNA in massage group was higher than that in model group (P＜ 0.05)., Conclusion: Massage can delay the atrophy of denervated skeletal muscle. The mechanism may be related to up-regulation of the expression of miR-23a and Akt mRNA, down-regulation of the expressions of MuRF1 and MAFbx mRNA, inhibition of protein degradation rate, and reduction of skeletal muscle protein degradation.

Objective: To observe the therapeutic effect of electroacupuncture (EA) of "Zusanli" (ST36) and " Ashi "-point on the healthy side (opposing needling) on muscular injury and expression of myogenin (myoG) and fast myosin skeletal heavy chain (Fast MyHC) proteins in the gastrocnemius muscle (GM) tissues in skeletal muscle contusion rats，so as to explore its mechanism underlying improvement of skeletal muscle injury., Methods: A total of 54 male SD rats were divided into normal control (n ＝ 6)，model ( n ＝24) and opposing needling (EA, n ＝24) groups. The latter two groups were further randomized into 3, 5, 7 and 14 d subgroups ( n ＝6 per subgroup). The skeletal muscle contusion model of the hind-limb was established by using a self-made striking device. EA (1 Hz/3 Hz，1－2 mA) was applied to ST36 and " Ashi "-point on the uninjured side of the hind-limb for 15 min every time, once a day for 3, 5, 7 and 14 days, respectively. The injured GM was harvested on the 3 rd, 5 th, 7 th and 14 th day after muscular contusion. The morphological changes of the injured GM and the mean cross-sectional areas (CSAs) of the neonatal muscle cells were observed by microscope after H．E. staining. The immunoactivity of desmin protein (myogenic marker protein of myoblast cell) of GM was detected by immunofluorescence stain on the 7 th day after injury, and the expression levels of myoG (on the 3 rd and 5 th day after injury) and fast MyHC protein of GM tissues (on the 7 th and 14 th day after injury) were detected by Western blot., Results: H．E. staining of GS tissue showed fewer neuronal myocytes with disordered arrangement at different sizes, and appearance of some collagenous fibers among the mesenchyme on day 7 and 14 after muscular contusion, which was relatively milder in the EA group. In the EA group, the CSA values of the neonatal muscle cells were significantly larger than those in the model group on the day 7 th ( P <0.05), 14 th ( P <0.001) after injury. On day 7 after muscular contusion, the desmin was found to express on the cellular membrane of GM in the normal control group, while in the model group, the desmin expressed mainly in the cellular plasma in the model group, and on the cellular membrane of neonatal myocytes in the EA group, respectively. The desmin positive myocytes showed disordered arrangement and different sizes after muscular contusion, whereas the situations of the EA group were close to those of the normal control group. Desmin expression was up-regulated in the EA group compared with the model group which was not significant difference ( P >0.05). On the 3 rd and 5 th day after muscular contusion, the expression level of myoG protein was significantly up-regulated in the model group compared with the normal control group ( P <0.001), and significantly up-regulated in the EA group than that in the model group ( P <0.001). On the 7 th and14 th day after contusion, the expression level of fast MyHC protein was significantly down-regulated in the model group relevant to the normal control group ( P <0.001), and markedly up-regulated in the EA group relevant to the model group ( P <0.01)．., Conclusion: EA of ST36 and " Ashi "-point on the contralateral limb can up-regulate the expression of myoG and fast MyHC proteins of GM in acute skeletal muscle contusion rats, which may contribute to its effect in promoting the repair of skeletal muscle injury.

Objective: To observe the effect of electroacupuncture (EA) on morphological changes of denervated gastrocnemius(GS) and the expression of fork-head protein(FOXO3A), muscle atrophy F-box(MAFbx)and myogenic differentiation antigen (Myod1) in sciatic nerve injury rats, so as to reveal its mechanism underlying improvement of myoatrophy., Methods: Eighteen male Sprague-Dawley rats were randomly divided into sham operation, model and EA groups ( n ＝6 per group). The model of gastrocnemius atrophy was established by crushing the right sciatic nerve. Then, EA (2 Hz) was applied to the right "Zusanli" (ST36) and "Huantiao" (GB30) for 10 min, once a day for 14 successive days. The wet weight of the GS on both sides was weighted to calculate the wet weight ratio (the injured side /the healthy side), and the cross-sectional area (CSA) and diameter of GS fibers were measured after H．E. staining. The expressions of FOXO3A, MAFbx and Myod1 protein and mRNA in the GS tissue were tested using Western blot and fluorescence quantitative PCR, separately., Results: Following modeling, the GS wet weight ratio, CSA and fiber diameter were smaller in the model group than those in the sham group ( P <0.01), and were significantly higher in the EA group than in the model group ( P <0.01). H．E. staining showed that the GS fibers became smaller and the myocyte got round in the model group, while the GS fibers were bigger and the myocyte was relatively regular in morphology in the EA group. After modeling, the expression levels of FOXO3A, MAFbx and Myod1 mRNA and protein were evidently higher in the model group ( P <0.01); Moreover, after EA treatment, modeling-induced increasing of expression levels of FOXO3A and MAFbx mRNA and protein were revised ( P <0.01), while the increased expression level of Myod1 was further up-regulated relavant to that in the model group ( P <0.01)．., Conclusion: EA of ST36 and GB30 can suppress the up-regulated expression of FOXO3A and MAFbx mRNA and protein and further promote the expression of Myod1 mRNA and protein in the GS tissue in rats with denervated GS atrophy, which may contribute to its function in relieving the myoatrophy, promoting the skeletal muscle protein hydrolysis and differentiation of satellite cells.

Hepatic stellate cells (HSCs) play a critical role in the pathogenesis and reversal of liver fibrosis. Targeting HSCs is of great significance in the treatment of hepatic fibrosis, and has attracted wide attention of scholars. Here we demonstrated that expression of geranylgeranyldiphosphate synthase (GGPPS) predominantly increased in HSCs in murine fibrotic liver. HSC-specific knockdown of GGPPS using vitamin A-coupled liposome carrying siRNA-ggpps decreased activation of HSCs and alleviated fiber accumulation in vivo . Furthermore, our in vitro studies showed that GGPPS was up-regulated during HSCs activation in TGF-β1-dependent manner. Inhibition of GGPPS suppressed TGF-β1 induced F-actin reorganization and HSCs activation in LX-2 cells. Further, we found that GGPPS regulated HSCs activation and liver fibrosis possibly by enhancing RhoA/Rock kinase signaling. So its concluded that GGPPS promotes liver fibrosis by activating HSCs, which may represent a potential target for anti-fibrosis therapies., Competing Interests: None.

Purpose: Psychologic depression has been shown to dysregulate the immune system and promote tumor progression. The aim of this study is to investigate how psychologic depression alters the immune profiles in prostate cancer., Experimental Design: We used a murine model of depression in Myc-CaP tumor-bearing immunocompetent FVB mice and Hi-myc mice presenting with spontaneous prostate cancer. Transwell migration and coculture assays were used to evaluate myeloid cell trafficking and cytokine profile changes evoked by Myc-CaP cells that had been treated with norepinephrine (NE), a major elevated neurotransmitter in depression. Chemoattractant, which correlated with immune cell infiltration, was screened by RNA-seq. The chemoattractant and immune cell infiltration were further confirmed using clinical samples of patients with prostate cancer with a high score of psychologic depression., Results: Psychologic depression predominantly promoted tumor-associated macrophage (TAM) intratumor infiltrations, which resulted from spleen and circulating monocytic myeloid-derived suppressor cell mobilization. Neuropeptide Y (NPY) released from NE-treated Myc-CaP cells promotes macrophage trafficking and IL6 releasing, which activates STAT3 signaling pathway in prostate cancer cells. Clinical specimens from patients with prostate cancer with higher score of depression revealed higher CD68 + TAM infiltration and stronger NPY and IL6 expression., Conclusions: Depression promotes myeloid cell infiltration and increases IL6 levels by a sympathetic-NPY signal. Sympathetic-NPY inhibition may be a promising strategy for patients with prostate cancer with high score of psychologic depression. See related commentary by Mohammadpour et al., p. 2363 ., (©2018 American Association for Cancer Research.)

Background: Abnormally activated mechanistic target of rapamycin (mTOR) pathway has been reported in several model animals with inherited metabolic myopathies (IMMs). However, the profiles of mTOR pathway in skeletal muscles from patients are still unknown. This study aimed to analyze the activity of mTOR pathway in IMMs muscles., Methods: We collected muscle samples from 25 patients with mitochondrial myopathy (MM), lipid storage disease (LSD) or Pompe disease (PD). To evaluate the activity of mTOR pathway in muscle specimens, phosphorylation of S6 ribosomal protein (p-S6) and p70S6 kinase (p-p70S6K) were analyzed by Western blotting and immunohistochemistry., Results: Western blotting results showed that p-p70S6K/p70S6K in muscles from LSD and MM was up-regulated when compared with normal controls (NC) (NC vs. LSD, U = 2.000, P = 0.024; NC vs. MM: U = 6.000, P = 0.043). Likewise, p-S6/S6 was also up-regulated in muscles from all three subgroups of IMMs (NC vs. LSD, U = 0.000, P = 0.006; NC vs. PD, U = 0.000, P = 0.006; NC vs. MM, U = 1.000, P = 0.007). Immunohistochemical study revealed that p-S6 was mainly expressed in fibers with metabolic defect. In MM muscles, most p-S6 positive fibers showed cytochrome C oxidase (COX) deficiency (U = 5.000, P = 0.001). In LSD and PD muscles, p-S6 was mainly overexpressed in fibers with intramuscular vacuoles containing lipid droplets (U = 0.000, P = 0.002) or basophilic materials (U = 0.000, P = 0.002)., Conclusion: The mTOR pathway might be activated in myofibers with various metabolic defects, which might provide evidence for mTOR inhibition therapy in human IMMs.

Objectives: JiangTangXiaoKe (JTXK) granule, a Chinese traditional herbal formula, has been clinically used and demonstrated to be beneficial in controlling high glucose and to relieve the symptoms of Type 2 diabetes mellitus patients for decades. In this study, we explored how loganin, one of the components in JTXK granule, mediated the anti-diabetic effect., Materials and Methods: We generate a cell model with the dysfunction of insulin secretion by over-expression FOXO1 in INS-1 cells. MTT method was used to detect cytotoxicity after treated with Loganin. ELISA analysis was used to examine insulin secretion. The expression levels of FOXO1 and Akt were evaluated by Western blot., Results: Treatment with Loganin did not change the expression level of FOXO1 in INS-1 cells, but increased phosphorylation of FOXO1 and inhibited the nuclear translocation and accumulation of FOXO1, which improved the insulin secretion of the cells. Mechanistically, we found PI3K/Akt signaling pathway involved in these effects, which were blocked by an Akt inhibitor, LY294002., Conclusion: Loganin mediated the subcellular distribution of FOXO1 via PI3K/Akt signaling pathway, which protected the function of insulin secretion in islet INS-1 cells., Competing Interests: The authors declare that they have no commercial or financial conflicts of interest with the contents of this article.

Research on mevalonate kinase deficiency has revealed that it may lead to the development of renal angiomyolipomas (RAMLs). Thus, it was suspected that geranylgeranyl pyrophosphate synthase (GGPPS), a key enzyme in the mevalonate pathway, may be involved in the development of RAMLs. In the present study, the expression of GGPPS in RAMLs and renal epithelioid angiomyolipomas (REAs) was assessed, and paraffin embedded specimens from 60 patients, including 9 cases with REA and 51 cases with RAML, were examined. Immunoreactivity was evaluated semi-quantitatively according to the intensity of staining and the percentage of positively stained cells. The results indicated that GGPPS was predominantly present in the cytoplasm, and REA tissues exhibited higher expression of GGPPS in the cytoplasm compared with RAML tissues. It was also identified that GGPPS was upregulated in TSC2-null cells, and inhibition of GGPPS could induce apoptosis of TSC2-null cells by autophagy. In conclusion, the increased expression of GGPPS in RAMLs and REAs indicated that mevalonate pathways may be involved in disease progression. GGPPS may serve as a potential therapeutic target and the current results may provide a novel therapeutic strategy for RAML and lymphangioleiomyomatosis.

Objective: To explore the effect of electroacupuncture(EA) on amyotrophia and expression of paired box7(Pax7), myogenic differentiation antigen-1 (Myod1), myogenin (Myog), myosin heavy chain- Ⅱa (Myh2), myosin heavy chain-Ⅱx (Myh1) and myosin heavy chain-Ⅰ (Myh7) of denervated gastrocnemius in rats with chronic constriction injury (CCI) of the right sciatic nerve, so as to explore its mechanisms underlying postponing development of amyotrophia., Methods: Sixty-six SD adult male rats were randomly divided into sham operation (sham) group ( n ＝24), model group ( n ＝24) and EA group ( n ＝18). The denervated muscle (gastrocnemius) atrophy model was established by CCI of the right sciatic nerve. EA (2 Hz，1.0 mA) was applied to the right "Zusanli"(ST36) and "Huantiao"(GB30) for 10 min, once a day, six times a week and for 1, 2 and 4 weeks, respectively. After complete dissection of bilateral gastrocnemius muscles, their wet weight levels were measured and the ratio of wet weight (＝that of the operation side/that of the non-operation side) was calculated, and the cross-sectional area (CSA) and diameter of the gastronemius were detected after fixation in 4% paraformaldehyde, sectioning, and H．E. staining. The expression levels of Pax7, Myod1, Myog, Myh2, Myh1 and Myh7 mRNAs in the gastrocnemius tissue after 3 weeks of modeling were detected with quantitative real time-PCR (qPCR)., Results: After 1 week of modeling, the ratios of wet weight of gastrocnemius and the CSA and fiber diameter at the 2 nd , 3 rd and 5 th week were significantly smaller in the model group than in the sham group ( P <0.05). The expression levels of Myod1 and Myog mRNAs were significantly up-regulated ( P <0.01), and those of Myh2, Myh1 and Myh7 considerably down-regulated in the model group compared with the sham group ( P <0.05, P <0.01). No significant changes were found in the expression levels of Pax7 mRNA after modeling and EA intervention ( P >0.05)．Following EA intervention, the CSA and diameterof the gastronemius were obviously increased ( P <0.05), and the expression levels of Myod1, Myog and Myh7 further markedly or remarkably up-regulated in comparison with the model group ( P <0.05, P <0.01). No significant changes were found in the ratio of wet weight of gastrocnemius at the 3 time-points, and the expression levels of Myh2 mRNA and Myh1 mRNA in the EA group relevant to the model group after 3 weeks of modeling ( P >0.05)., Conclusion: EA treatment may delay gastrocnemius atrophy in CCI rats, which is possibly associated with its effects in up-regulating the expression of Myod1, Myog and Myh7 mRNAs to control the differentiation of the satellite cells and the muscle fiber type transformation.

[This corrects the article DOI: 10.18632/oncotarget.18138.].

Objective: To explore the effect of electroacupuncture (EA) on the expression of synovial AMP-activated protein kinase (AMPK) protein α， arginase-1 mRNA, nitric oxide synthase 2 (NOS 2) mRNA, NOD-like receptor protein 3 (NLRP 3) mRNA, and interleukin-1 β (IL-1 β) mRNA in acute gouty arthritis (AGA) rats, so as to explore its mechanisms underlying improvement of AGA via M 1/M 2 macrophage polarization., Methods: Male Wistar rats were randomly divided into normal control, model, medication (colchicine) and EA groups ( n ＝15 rats in each group). The AGA model was established by injection of sodium urate crystal (MSU) suspension (0.2 mL) into the articular cavity of the left knee. The rats of the normal control group received articular injection of normal saline (0.2 mL) of the left knee, and those of the medication group were treated by gavage of the colchicine (0.3 mg•kg －1 •d －1 ) once daily for 7 days. EA (2 Hz/10 Hz, 1.0 mA) was applied to "Zusanli"(ST 36) and "Sanyinjiao" (SP 6) of the left hind limb for 10 min, once daily for 7 days. The inflammatory conditions of the synovial membrane tissue of the left knee joint were observed by H．E. staining. The expression levels of phosphorylated AMPKα (p-AMPKα) protein, and arginase-1 (a maker of M 2 macrophages) mRNA, NOS 2 (a maker of M 1 macrophages) mRNA, NLRP 3 mRNA, and IL-1 β mRNA in the knee joint synovial tissue were detected by Western blot and quantitative real-time PCR, respectively., Results: Compared with the normal group, the inflammatory cell infiltration of the synovial tissue was more severe, the expression of p-AMPKα protein was significantly decreased ( P <0.01), and the expression levels of arginase-1, NOS 2, IL-1 β and NLRP 3 mRNAs were considerably increased in the model group ( P <0.01). The expression levels of p-AMPKα protein and arginase-1 mRNA were significantly up-regulated, and those of NOS 2, IL-1 β and NLRP 3 mRNAs obviously down-regulated in both EA and medication groups relevant to the model group ( P <0.01, P <0.05), suggesting an increase of M 2 macrophage and a decrease of M 1 macrophage activity after EA. No significant differences were found between the EA and medication groups in up-regulating p-AMPKα expression and in down-regulating NOS 2, IL-1 β and NLRP 3 mRNA expression ( P >0.05), except higher up-regulation of arginase-1 mRNA in the medication group ( P <0.05)．., Conclusion: EA intervention can up-regulate the expression of arginase-1 mRNA and p-AMPKα protein, and down-regulate the expression of NOS 2, IL-1 β and NLRP 3 mRNAs in synovial tissues in AGA rats, which may contribute to its anti-inflammatory effect by promoting conversion of macrophages from M 1 pro-inflammatory phenotype to M 2 anti-inflammatory phenotype.