Genome-Wide Identification of Eucalyptus Heat Shock Transcription Factor Family and Their Transcriptional Analysis under Salt and Temperature Stresses.

Heat shock transcription factors (HSFs) activate heat shock protein gene expression by binding their promoters in response to heat stress and are considered to be pivotal transcription factors in plants. Eucalyptus is a superior source of fuel and commercial wood. During its growth, high temperature or other abiotic stresses could impact its defense capability and growth. Hsf genes have been cloned and sequenced in many plants, but rarely in Eucalyptus. In this study, we used bioinformatics methods to analyze and identify Eucalyptus Hsf genes, their chromosomal localization and structure. The phylogenetic relationship and conserved domains of their encoded proteins were further analyzed. A total of 36 Hsf genes were identified and authenticated from Eucalyptus, which were scattered across 11 chromosomes. They could be classified into three classes (A, B and C). Additionally, a large number of stress-related cis-regulatory elements were identified in the upstream promoter sequence of HSF, and cis-acting element analysis indicated that the expression of EgHsf may be regulated by plant growth and development, metabolism, hormones and stress responses. The expression profiles of five representative Hsf genes, EgHsf4, EgHsf9, EgHsf13, EgHsf24 and EgHsf32, under salt and temperature stresses were examined by qRT-PCR. The results show that the expression pattern of class B genes (EgHsf4, EgHsf24 and EgHsf32) was more tolerant to abiotic stresses than that of class A genes (EgHsf9 and EgHsf13). However, the expressions of all tested Hsf genes in six tissues were at different levels. Finally, we investigated the network of interplay between genes, and the results suggest that there may be synergistic effects between different Hsf genes in response to abiotic stresses. We conclude that the Hsf gene family played an important role in the growth and developmental processes of Eucalyptus and could be vital for maintaining cell homeostasis against external stresses. This study provides basic information on the members of the Hsf gene family in Eucalyptus and lays the foundation for the functional identification of related genes and the further investigation of their biological functions in plant stress regulation.

Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway.

BACKGROUND/AIMS: This study aims to examine the effect of long noncoding RNA HOST2 (LncRNA HOST2) on epithelial-mesenchymal transition (EMT), proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells via activation of the JAK2-STAT3 signaling pathway. METHODS: HCC and para-cancerous tissues were collected from 136 HCC patients. Immunohistochemistry was used to detect the expression of JAK2 and STAT3. HCC SMMC7721 cells were grouped into blank, negative control (NC), HOST2 mimic and HOST2 inhibitor groups. The mRNA and protein expression levels of HOST2, JAK2, STAT3, E-cadherin, vimentin, Snail, Slug, Twist and Zeb1 in tissues and cells were determined by reverse transcription -quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. An MTT assay, scratch test and Transwell assay were applied to measure cell proliferation, migration and invasion, respectively. RESULTS: The levels of JAK2, STAT3 and vimentin were higher in HCC tissues, while the expression of E-cadherin was lower in HCC tissues compared with para-cancerous tissues. The silencing of HOST2 significantly decreased cell proliferation, migration and invasion, reduced the levels of HOST2, JAK2, STAT3 and vimentin, and elevated the expression of E-cadherin. HOST2 silencing also decreased the levels of Snail, Slug and Twist but increased the level of Zeb1 protein, while the opposite findings were observed in the HOST2 mimic group. CONCLUSION: These results reveal a possible mechanism in HCC in which LncRNA HOST2 may increase EMT and enhance proliferation, invasion and metastasis of HCC cells via activation of the JAK2-STAT3 signaling pathway.

Exposure to Radon and Kidney Cancer: A Systematic Review and Meta-analysis of Observational Epidemiological Studies.

OBJECTIVE: To evaluate the possible association between radon exposure and kidney cancer. METHODS: We performed a systematic review and a meta-analysis based on random effect models to provide a pooled association measure. RESULTS: We subjected 8 studies (overall relative risks and 95% confidence intervals: 1.01, 0.72 to 1.43, I2 = 64.4%) to meta-analysis. Subgroup analysis revealed a marginally significant association between radon exposure and kidney cancer in studies conducted in Europe. Two population-based studies provided no evidence for the increased risk of kidney cancer in the general population. CONCLUSION: The association between radon and kidney cancer remains unclear but cannot be excluded because of its biological plausibility and the limited number and quality of existing studies. Additional data from the general population and well-designed miner cohort studies are needed to reveal the real relationship between radon exposure and kidney cancer.

Exploring the FGFR3-related oncogenic mechanism in bladder cancer using bioinformatics strategy.

BACKGROUND: Aberrant activation of fibroblast growth factor receptor 3 (FGFR3) is frequently observed in bladder cancer, but how it involved in carcinogenesis is not well understood. The current study was aimed to investigate the underlying mechanism on the progression of bladder cancer. METHODS: The GSE41035 dataset downloaded from Gene Expression Omnibus was used to identify the differentially expressed genes (DEGs) between bladder cancer cell line RT112 with or without depletion of FGFR3, and gene ontology enrichment analysis was performed. Then, FGFR3-centered protein-protein interaction (PPI) and regulatory networks were constructed. Combined with the data retrieved from GSE31684, prognostic makers for bladder cancer were predicted. RESULTS: We identified a total of 2855 DEGs, and most of them were associated with blood vessel morphogenesis and cell division. In addition, KIAA1377, POLA2, FGFR3, and EPHA4 were the hub genes with high degree in the FGFR3-centered PPI network. Besides, 17 microRNAs (miRNAs) and 6 transcriptional factors (TFs) were predicted to be the regulators of the nodes in PPI network. Moreover, CSTF2, POLA1, HMOX2, and EFNB2 may be associated with the prognosis of bladder cancer patient. CONCLUSIONS: The current study may provide some insights into the molecular mechanism of FGFR3 as a mediator in bladder cancer.

IRF5 governs macrophage adventitial infiltration to fuel abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the expansion of the aortic wall. One of the most significant features is the infiltration of macrophages in the adventitia, which drives vasculature remodeling. The role of macrophage-derived interferon regulatory factor 5 (IRF5) in macrophage infiltration and AAA formation remains unknown. RNA sequencing of AAA adventitia identified Irf5 as the top significantly increased transcription factor that is predominantly expressed in macrophages. Global and myeloid cell-specific deficiency of Irf5 reduced AAA progression, with a marked reduction in macrophage infiltration. Further cellular investigations indicated that IRF5 promotes macrophage migration by direct regulation of downstream phosphoinositide 3-kinase γ (PI3Kγ, Pik3cg). Pik3cg ablation hindered AAA progression, and myeloid cell-specific salvage of Pik3cg restored AAA progression and macrophage infiltration derived from Irf5 deficiency. Finally, we found that IRF5 and PI3Kγ expression in the adventitia is significantly increased in patients with AAA. These findings reveal that the IRF5-dependent regulation of PI3Kγ is essential for AAA formation.

Correlation between age and curative effects of selective dorsal neurectomy for primary premature ejaculation.

BACKGROUND: The use of selective dorsal neurectomy (SDN) as a surgical treatment of premature ejaculation (PE) has increased for many years in Asian countries. OBJECTIVES: To investigate the correlation between age and curative effects of SDN in primary premature ejaculation (PPE) in mainland China. MATERIAL AND METHODS: From September 2016 to September 2020, 65 patients with PPE treated with SDN were selected for study. All of the patients were followed up from 12 to 56 (30.07 ±13.48) months. They were divided into 3 groups according to age: group A (22-30 years, n = 23), group B (31-37 years, n = 20) and group C (38-45 years, n = 22). The 5-item version of the International Index of Erectile Function (IIEF-5) and Premature Ejaculation Diagnostic Tool (PEDT) results, erectile rigidity grade, intravaginal ejaculation latency time (IELT), ejaculation control abilities (ECA) scores, and sexual intercourse satisfaction (SIS) scores were assessed in the 3 groups before and after operation to evaluate the clinical efficacy of surgery. RESULTS: Fifty-nine patients were finally followed up. The IIEF-5 scores and erectile rigidity grade of group A was significantly higher than that of groups B and C, both before and after surgery. The change of PEDT scores in group A was significantly higher than in groups B and C; the difference was statistically significant (p < 0.05). The IELT, ECA and SIS scores in group A were significantly higher than in groups B and C (p < 0.05). Operational efficiency ratio in groups B and C (65%, 70%) was significantly lower than in group A (95.24%). CONCLUSIONS: The SDN as a treatment of PPE in different age groups allowed to achieve certain results. The highest surgical efficiency (95.24%) was observed in the 22-30 years age group and the lowest (65%) in the 38-45 years age group. Therefore, we believe that the best time for surgery is between 22 and 30 years of age.

The evolutionarily conserved arginyltransferase 1 mediates a pVHL-independent oxygen-sensing pathway in mammalian cells.

The response to oxygen availability is a fundamental process concerning metabolism and survival/death in all mitochondria-containing eukaryotes. However, the known oxygen-sensing mechanism in mammalian cells depends on pVHL, which is only found among metazoans but not in other species. Here, we present an alternative oxygen-sensing pathway regulated by ATE1, an enzyme ubiquitously conserved in eukaryotes that influences protein degradation by posttranslational arginylation. We report that ATE1 centrally controls the hypoxic response and glycolysis in mammalian cells by preferentially arginylating HIF1α that is hydroxylated by PHD in the presence of oxygen. Furthermore, the degradation of arginylated HIF1α is independent of pVHL E3 ubiquitin ligase but dependent on the UBR family proteins. Bioinformatic analysis of human tumor data reveals that the ATE1/UBR and pVHL pathways jointly regulate oxygen sensing in a transcription-independent manner with different tissue specificities. Phylogenetic analysis suggests that eukaryotic ATE1 likely evolved during mitochondrial domestication, much earlier than pVHL.

Heat conduction in chain polymer liquids: molecular dynamics study on the contributions of inter- and intramolecular energy transfer.

In this paper, the molecular mechanisms which determine the thermal conductivity of long chain polymer liquids are discussed, based on the results observed in molecular dynamics simulations. Linear n-alkanes, which are typical polymer molecules, were chosen as the target of our studies. Non-equilibrium molecular dynamics simulations of bulk liquid n-alkanes under a constant temperature gradient were performed. Saturated liquids of n-alkanes with six different chain lengths were examined at the same reduced temperature (0.7T(c)), and the contributions of inter- and intramolecular energy transfer to heat conduction flux, which were identified as components of heat flux by the authors' previous study [J. Chem. Phys. 128, 044504 (2008)], were observed. The present study compared n-alkane liquids with various molecular lengths at the same reduced temperature and corresponding saturated densities, and found that the contribution of intramolecular energy transfer to the total heat flux, relative to that of intermolecular energy transfer, increased with the molecular length. The study revealed that in long chain polymer liquids, thermal energy is mainly transferred in the space along the stiff intramolecular bonds. This finding implies a connection between anisotropic thermal conductivity and the orientation of molecules in various organized structures with long polymer molecules aligned in a certain direction, which includes confined polymer liquids and self-organized structures such as membranes of amphiphilic molecules in water.

AMPK: Potential Therapeutic Target for Vascular Calcification.

Vascular calcification (VC) is an urgent worldwide health issue with no available medical treatment. It is an active cell-driven process by osteogenic differentiation of vascular cells with complex mechanisms. The AMP-activated protein kinase (AMPK) serves as the master sensor of cellular energy status. Accumulating evidence reveals the vital role of AMPK in VC progression. AMPK is involved in VC in various ways, including inhibiting runt-related transcription factor 2 signaling pathways, triggering autophagy, attenuating endoplasmic reticulum stress and dynamic-related protein 1-mediated mitochondrial fission, and activating endothelial nitric oxide synthase. AMPK activators, like metformin, are associated with reduced calcification deposits in certain groups of patients, indicating that AMPK is a potential therapeutic target for VC.

The Association Between Metformin Treatment and Outcomes in Type 2 Diabetes Mellitus Patients With Heart Failure With Preserved Ejection Fraction: A Retrospective Study.

Background: Metformin is the first-line antidiabetic medication for type 2 diabetes mellitus (T2DM). However, the association between metformin and outcomes in T2DM patients with heart failure with preserved ejection fraction (HFpEF) is still unknown. We aimed to explore the association between metformin and adverse outcome in T2DM patients with HFpEF. Methods: A total of 372 T2DM patients with HFpEF hospitalized from January 1, 2013, to December 31, 2017, were included in this retrospective cohort study. There were 113 and 259 subjects in metformin and non-metformin group, respectively. Subjects were followed up for all-cause mortality, cardiovascular death, all-cause hospitalization, and heart failure hospitalization. Results: The median follow-up period was 47 months. Eleven patients (2.49% per patient-year) in the metformin group and 56 patients (5.52% per patient-year) in the non-metformin group deceased during follow-up (P = 0.031). However, a multivariable Cox regression failed to show that metformin was an independent factor of all-cause mortality [HR (95% CI) = 0.682 (0.346-1.345); P = 0.269]. A subgroup analysis revealed a significant association between metformin and all-cause mortality in patients with a higher hemoglobin A1c (HbA1c) level (HbA1c ≥7%) [HR (95% CI) = 0.339 (0.117-0.997); P = 0.045]. The 4-year estimated number needed to treat (NNT) with metformin compared with non-metformin for all-cause mortality was 12 in all populations and 8 in the HbA1c ≥7% subgroup. Conclusions: Metformin was not independently associated with clinical outcomes in patients with T2DM and HFpEF, but was associated with lower all-cause mortality in the subgroup of patients with poor glycemic control. Prospective, randomized controlled trials are needed to further verify these findings.

The effects of gluten protein substation on chemical structure, crystallinity, and Ca in vitro digestibility of wheat-cassava snacks.

Gluten protein based snacks have been a major concern for allergen, low nutrition and physio-chemical properties. In this study, wheat flour (WF) was replaced with cassava starch (CS) at different levels [10, 20, 30, 40 and 50%(w/w)] to prepare fried snacks. The addition of CS significantly (P < 0.05) increased hardness and pasting properties while gluten network, oil uptake, water holding capacity, and expansion were decreased. Fourier transform infrared spectroscopy revealed that the secondary structure of amide I, α-helix (1650-1660 cm-1), along with amide II region (1540 cm-1) changed when CS was added. Starch-protein complex was identified by X-ray diffraction analysis while no starch-protein-lipid complex was observed. The micrographs from scanning electron microscopy showed that starch-protein matrix was interrupted when ≥40%(w/w) CS was added. Furthermore, in vitro calcium bioavailability was decreased slightly with the addition of CS. The results suggest the feasibility of adding 40% CS as an alternative to WF in snacks.

[Multiglycosides of Tripterygium wilfordii increase sperm apoptosis in male rats].

OBJECTIVE: To study the effect of multiglycosides of Tripterygium wilfordii (GTW) on sperm apoptosis in male rats and its possible mechanisms. METHODS: Sixteen male SD rats were equally assigned to two groups to receive GTW and carboxymethylcellulose (CMC) intragastrically, both at 20 mg/(kg x d) for 6 weeks. Then the epididymal sperm was collected for the measurement of the apoptosis rate, sperm membrane lipid fluidity and the contents of NO, MDA and SOD by flow cytometry and spectrophotometric determination. RESULTS: After 6 weeks of medication, the GTW group showed a significant increase in sperm apoptosis and contents of NO and MDA (P < 0.01) and a remarkable decrease in sperm membrane lipid fluidity (P < 0.05) and SOD content (P < 0.01) as compared with the CMC control group. CONCLUSION: GTW can damage sperm membrane lipid peroxidation and sperm membrane structure, increase sperm apoptosis, and reduce sperm membrane lipid fluidity.

Early Aortic Valve Replacement vs. Conservative Management in Asymptomatic Severe Aortic Stenosis Patients With Preserved Ejection Fraction: A Meta-Analysis.

Background: Aortic stenosis (AS) is the most common valvular disease in developed countries. Until now, the specific timing of intervention for asymptomatic patients with severe aortic stenosis and preserved ejection fraction remains controversial. Methods: A systematic search of four databases (Pubmed, Web of science, Cochrane library, Embase) was conducted. Studies of asymptomatic patients with severe AS or very severe AS and preserved left ventricular ejection fraction underwent early aortic valve replacement (AVR) or conservative care were included. The end points included all-cause mortality, cardiac mortality, and non-cardiac mortality. Results: Four eligible studies were identified with a total of 1,249 participants. Compared to conservative management, patients who underwent early AVR were associated with lower all-cause mortality, cardiac mortality, and non-cardiac mortality rate (OR 0.16, 95% CI 0.09-0.31, P < 0.00001; OR 0.12, 95% CI 0.02-0.62, P = 0.01; OR 0.36, 95% CI 0.21-0.63, P = 0.0003, respectively). Conclusions: Early AVR is preferable for asymptomatic severe AS patients with preserved ejection fraction.

[Regional anatomy of the dorsal penile nerve and its clinical significance].

OBJECTIVE: To investigate the number, course and distribution of normal dorsal penile nerves and their clinical significance for selective neurectomy of the dorsal penile nerve in the treatment of primary premature ejaculation. METHODS: We dissected 38 cadaveric adult penises and recorded the number, course and distribution of the dorsal penile nerves. A total of 314 cases of primary premature ejaculation underwent selective neurectomy of the dorsal penile nerve. The patients ranged between 20 and 45 years in age and from 1 to 22 years in disease course. RESULTS: The dorsal penile nerves were distributed in parallel bilaterally in all the cadaveric penises and branched into the ventral side in 4 of them. The total number of dorsal penile nerves was (3.6 +/- 1.2) in the 38 cadaveric penises, 7 in 1 case, 6 in 1 case, 5 in 6 cases, 4 in 9 cases, 3 in 14 cases and 2 in 7 cases, while that of the 314 patients with primary premature ejaculation was (7.0 +/- 1.9), 5 in 64 cases, 6 in 56 cases, 7 in 52 cases, 8 in 40 cases, 9 in 33 cases, 10 in 28 cases, 11 in 25 cases, 12 in 11 cases and 13 in 5 cases. Selective neurectomy of the dorsal penile nerve achieved an intravaginal ejaculation latency of (4.31 +/- 1.87) minutes and sexual satisfaction rate of (61 +/- 17) %, significantly different from those before the operation ([1.24 +/- 0.32] min, [23 +/- 6] %; all P < 0.01). CONCLUSION: The abnormal increase of dorsal penile nerves possibly lies at the bottom of the pathogenesis of primary premature ejaculation. Selective neurectomy of the dorsal penile nerve is safe and effective for the treatment of primary premature ejaculation.

A case of mental retardation caused by a frameshift variant of SYNGAP1 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with mental retardation.@*METHODS@#Whole exome sequencing was carried out for the child. Candidate variant was screened based on his clinical features and verified by Sanger sequencing.@*RESULTS@#The child was found to harbor a c.995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant in the SYNGAP1 gene. Bioinformatic analysis suggested it to be pathogenic. The same variant was not detected in either parent.@*CONCLUSION@#The c.995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant of the SYNGAP1 gene probably underlay the mental retardation in this child. Above finding has expanded the spectrum of SYNGAP1 gene variants and provided a basis for the diagnosis and treatment for this child.

Safety of butylphthalide and edaravone in patients with ischemic stroke: a multicenter real-world study / 老年心脏病学杂志（英文版）

BACKGROUND@#Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations.@*METHODS@#In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively.@*RESULTS@#81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count.@*CONCLUSIONS@#In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

Research progress on dyadic coping of pregnant women and their spouses / 中国实用护理杂志

This article reviewed the concept and theoretical models of dyadic coping, as well as the related factors of dyadic coping of pregnant women and their spouses, and introduced the application status of dyadic coping in pregnant women and their spouses. To provide a reference for constructing a dyadic coping intervention plan between pregnant women and their spouses based on the cultural background of China.

Evaluation of in vitro antifungal activity of berberine against Talaromyces marneffei in yeast phase / 中华皮肤科杂志

Objective:To evaluate the in vitro antifungal activity of berberine against Talaromyces marneffei (TM) in yeast phase. Methods:There were 21 TM strains, including l standard strain (ATCC22019), 10 clinical isolates and 10 isolates from wild bamboo rats. TM strain suspensions at a concentration of (1 - 5) × 10 3 colony-forming units/ml were incubated in microdilution plates containing difierent concentrations of berberine, fluconazole, itraconazole, voriconazole, amphotericin B or caspofungin at 37 ℃ for 48 hours. Meanwhile, the wells containing only culture media and TM strains but without antifungal drugs served as the positive control group, and those containing only culture media served as the negative control group. The minimum inhibitory concentrations (MICs) of antifungal drugs against TM yeasts were determined according to the Clinical and Laboratory Standards Institute (CLSI) broth microdilution susceptibility method (M27-A3 document) . Results:The MICs of the above antifungal drugs were all within the reference ranges for the quality control strain (ATCC22019), and TM strains grew well in the positive control wells. The MIC ranges of berberine, itraconazole, voriconazole, amphotericin B and caspofungin against TM strains were 32 - 64 mg/L, 0.06 - 0.125 mg/L, 0.06 - 0.125 mg/L, 1 - 2 mg/L and 16 - 32 mg/L respectively; the MIC range of fluconazole was 2 - 4 mg/L for non-resistant strains, and 128 mg/L for fluconazole-resistant clinical strains.Conclusion:Berberine exhibits antifungal activity against TM in yeast phase.

[Sleeve circumcision and preputioplasty with modified incision].

OBJECTIVE: To evaluate the sleeve circumcision and preputioplasty with modified incision for the treatment of patients with phimosis or redundant prepuce. METHODS: Five hundred and seventy-six patients with phimosis or redundant prepuce underwent operations of sleeve circumcision or preputioplasty with modified incision. The conventional incision was modified and changed into two opposite tortuous incisions. RESULTS: The operation with modified incision had the following advantages: less blood loss, slight postoperative edema, no secondary bleeding or infection, quick recovery and good appearance of the penis. CONCLUSION: The sleeve circumcision and preputioplasty with modified incision is an excellent therapeutic option for phimosis and redundant prepuce.