Application value of adrenal venous sampling in the surgical treatment of primary aldosteronism.

The diagnosis of primary aldosteronism (PA) is critical for determining treatment strategies. The aim of the present study was to investigate the clinical value of preoperative adrenal venous sampling (AVS) for determining the benefit of PA surgery. Patients diagnosed with PA at Liaocheng People's Hospital (Liaocheng, China) between January 2015 and December 2020 were selected and divided into two groups: Group A underwent adrenal computed tomography (CT) only, whereas Group B underwent adrenal CT and successful AVS. Subsequently, the improvement rate of adrenal CT and adrenal CT + AVS in the treatment of PA was compared. A total of 164 patients were included, with an average age of 46.69±13.64 years. There were 62 patients in Group A and 102 in Group B. Among the patients diagnosed with unilateral lesions on adrenal CT scan, 82.61% of patients in group A and 87.72% in group B showed improvement; however, the difference was not significant (χ2=0.534, P=0.465). Among the patients diagnosed with bilateral lesions on adrenal CT images, 62.50% of patients in Group A and 91.11% of patients in Group B showed improvement (P=0.019). In conclusion, unilateral adrenal lesions detected by CT did not benefit significantly from surgical decision-making after AVS. AVS should be advised for all patients with bilateral adrenal PA who are willing to undergo adrenal surgery, which is conducive to correct lateral segmentation and improve treatment choices.

Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 2: Modulation of hypoxia, redox status, and mitochondrial protection in a neuroblastoma cell line, SH-SY5Y.

OBJECTIVE: To examine the mitochondrial protective effects of icariin, naringenin, kaempferol, and formononetin, potentially active agents in Bu-Shen-Jian-Pi formula (BSJP) identified using network pharmacology analysis. MATERIALS AND METHODS: Mitochondrial protection activity was determined using a hypoxia-reoxygenation in vitro model based on the neuroblastoma cell line SH-SY5Y and measurements of anti-ferroptotic activity. RESULTS: Icariin, naringenin, kaempferol, and formononetin showed mitochondrial protective activity involving diverse signaling pathways. The cytoprotective effects of formononetin depended on the inhibition of ferroptosis. Hypoxia-reoxygenation stimulation induced ferroptosis in SH-SY5Y cells. DISCUSSION: Ferroptosis is a key mechanism in nervous system diseases and is associated with hypoxia-reoxygenation injury. Naringenin and kaempferol were devoid of anti-ferroptotic activity. CONCLUSION: Evidence has been obtained showing that the core components: icariin, naringenin, kaempferol, and formononetin in BSJP formula have anti-hypoxic and mitochondrial protective activity of potential clinical importance in the treatment of amyotrophic lateral sclerosis and patients with symptoms of hypoxia.

Red Room-Temperature Phosphorescence Supramolecular Assemblies Based on Cucurbit[7]uril: Reversible Temperature Stimulation Response and Cell-Specific Silver Ion Imaging.

Solid-state materials with efficient room-temperature phosphorescence (RTP) emission have been widely used in materials science, and organic RTP-emitting systems with heavy-metal doping in aqueous solutions have attracted much attention in recent years. A novel supramolecular interaction was induced by host-guest assembly using cucurbit[7]uril (Q[7]) as the host and brominated naphthalimide phosphor as the guest. This interaction was further enhanced through synergistic chelation stimulated by analytical silver ion complexation. This approach facilitated the system's structural rigidity, intersystem crossing, and oxygen shielding. We achieved deep red phosphorescence emission in aqueous solution and ambient conditions along with quantitative determination of silver ions. The new complex exhibited good reversible thermoresponsive behavior and was successfully applied for the first time to target phosphorescence imaging of silver ions in the mitochondria of A549 cancer cells. These results are beneficial for constructing novel RTP systems with stimulus-responsive luminescence in aqueous solution, contributing to future research in bioimaging, detection, optical sensors, and thermometry materials.

Disruption of T-box transcription factor eomesa results in abnormal development of median fins in Oujiang color common carp Cyprinus carpio.

Median fins are thought to be ancestors of paired fins which in turn give rise to limbs in tetrapods. However, the developmental mechanisms of median fins remain largely unknown. Nonsense mutation of the T-box transcription factor eomesa in zebrafish results in a phenotype without dorsal fin. Compared to zebrafish, the common carp undergo an additional round of whole genome duplication, acquiring an extra copy of protein-coding genes. To verify the function of eomesa genes in common carp, we established a biallelic gene editing technology in this tetraploidy fish through simultaneous disruption of two homologous genes, eomesa1 and eomesa2. We targeted four sites located upstream or within the sequences encoding the T-box domain. Sanger sequencing data indicated the average knockout efficiency was around 40% at T1-T3 sites and 10% at T4 site in embryos at 24 hours post fertilization. The individual editing efficiency was high to about 80% at T1-T3 sites and low to 13.3% at T4 site in larvae at 7 days post fertilization. Among 145 mosaic F0 examined at four months old, three individuals (Mutant 1-3) showed varying degrees of maldevelopment in the dorsal fin and loss of anal fin. Genotyping showed the genomes of all three mutants were disrupted at T3 sites. The null mutation rates on the eomesa1 and eomesa2 loci were 0% and 60% in Mutant 1, 66.7% and 100% in Mutant 2, and 90% and 77.8% in Mutant 3, respectively. In conclusion, we demonstrated a role of eomesa in the formation and development of median fins in Oujiang color common carp and established an method that simultaneously disrupt two homologous genes with one gRNA, which would be useful in genome editing in other polyploidy fishes.

A novel approach for quantitative determination of cellulose content in tobacco via 2D HSQC NMR spectroscopy.

Cellulose is an important component of tobacco (Nicotiana tabacum L.) cell walls, which can be precursors for many harmful compounds in smoke. Traditional cellulose content analysis methods involve sequential extraction and separation steps, which are time-consuming and environmentally unfriendly. In this study, a novel method was first introduced to analyze cellulose content in tobacco via two-dimensional heteronuclear single quantum coherence (2D HSQC) NMR spectroscopy. The method was based on derivatization approach to allow the dissolution of insoluble polysaccharide fractions of tobacco cell walls in DMSO­d6/pyridine-d5 (4:1 v/v) for NMR analysis. The NMR results suggested that besides the main NMR signals of cellulose, partial signals of hemicellulose including mannopyranose, arabinofuranose, and galactopyranose units could also be identified. In addition, the utilization of relaxation reagents has proved to be an effective way to improve the sensitivity of 2D NMR spectroscopy, which was beneficial for quantification of biological samples with limited quantities. To overcome the limitations of quantification using 2D NMR, the calibration curve of cellulose with 1,3,5-trimethoxybenzene as internal reference was constructed and thus the accurate measurement of cellulose in tobacco was achieved. Compared with the chemical method, the interesting method was simple, reliable, and environmentally friendly, which provided a new insight for quantitative determination and structure analysis of plant macromolecules in complex samples.

Changes in Macrophage Polarization During Tendon-to-Bone Healing After ACL Reconstruction With Insertion-Preserved Hamstring Tendon: Results in a Rabbit Model.

Background: Decreasing the proinflammatory M1 macrophages or shifting the polarization status from M1 to M2 phenotype is thought to be beneficial for tendon-to-bone healing. In anterior cruciate ligament reconstruction (ACLR), using an insertion-preserved hamstring tendon (IP-HT) graft compared with a free hamstring tendon (FHT) graft has been shown to reduce graft necrosis and improve healing. However, the role of macrophage polarization at the tendon-to-bone interface is unclear. Hypothesis: ACLR using IP-HT graft would facilitate the phenotype shift from M1 to M2 macrophages at the tendon-to-bone interface. Study Design: Controlled laboratory study. Methods: Unilateral ACLR was performed on 42 healthy New Zealand White rabbits (study group, 21 rabbits with IP-HT graft; control group, 21 rabbits with FHT graft). At days 1, 3, and 7 and weeks 3, 6, 12, and 24 postoperatively, 3 rabbits in each group were sacrificed to investigate and compare the expression of surrogate markers for M1 macrophages (inducible nitric oxide synthase [iNOS] and tumor necrosis factor α [TNF-α]) and M2 macrophages (CD206 and transforming growth factor ß [TGF-ß]) via immunohistochemical staining and evaluation. Results: In the control group, the percentage of iNOS- and TNF-α-positive cells from postoperative day 7 and week 3 increased then decreased by week 6; positive expression of CD206 and TGF-ß was weaker and peaked at 3 weeks postoperatively. In the study group, high CD206- and TGF-ß-positive expression was observed from weeks 3 to 12 and peaked at week 6, and positive expression of iNOS- and TNF-α was weaker and peaked on day 7. At both 7 days and 3 weeks, the percentages of iNOS- and TNF-α-positive cells in the control group were both significantly higher than in the study group (P ≤ .04 for all). At 6 weeks, the percentages of CD206- and TGF-ß-positive cells in the study group were both significantly higher than in the control group (P = .02 and P = .04, respectively). Conclusion: More expression of surrogate markers for M2 macrophages was observed in the tendon-to-bone healing process after ACLR using IP-HT versus FTP graft. Clinical Relevance: Using IP-HT grafts in ACLR may facilitate postoperative healing by shifting the local status of macrophage polarization at the tendon-to-bone interface.

Radial oscillation and translational motion of a gas bubble in a micro-cavity.

According to classical nucleation theory, a gas nucleus can grow into a cavitation bubble when the ambient pressure is negative. Here, the growth process of a gas nucleus in a micro-cavity was simplified to two "events", and the full confinement effect of the surrounding medium of the cavity was considered by including the bulk modulus in the equation of state. The Rayleigh-Plesset-like equation of the cavitation bubble in the cavity was derived to model the radial oscillation and translational motion of the cavitation bubble in the local acoustic field. The numerical results show that the nucleation time of the cavitation bubble is sensitive to the initial position of the gas nucleus. The cavity size affects the duration of the radial oscillation of the cavitation bubble, where the duration is shorter for smaller cavities. The equilibrium radius of a cavitation bubble grown from a gas nucleus increases with increasing size of the cavity. There are two possible types of translational motion: reciprocal motion around the center of the cavity and motion toward the cavity wall. The growth process of gas nuclei into cavitation bubbles is also dependent on the compressibility of the surrounding medium and the magnitude of the negative pressure. Therefore, gas nuclei in a liquid cavity can be excited by acoustic waves to form cavitation bubbles, and the translational motion of the cavitation bubbles can be easily observed owing to the confining influence of the medium outside the cavity.

Losartan Attenuates Insulin Resistance and Regulates Browning Phenomenon of White Adipose Tissue in ob/ob Mice.

Insulin resistance (IR) is a villain role to the pathology of fatty liver diseases implicated in adipose tissue dysfunction, which is characterized by lipid droplets (LDs) accumulation and hypoxia-inducible factor 1α (HIF1α) related macrophage infiltration. HIF1α is required for its lipogenic actions in adipocytes, while and it regulates M1 and M2 polarization features of macrophages. Losartan has been shown to be an insulin sensitizer in obese states, actions involving in HIF1α signaling. However, the exact mechanisms accounting for these effects have not been fully elucidated. Therefore, GTT, ITT, and HOMA-IR were identified losartan alleviated IR signaling in obese mice. This alleviation may through inhibits HIF1α by suppressing STAT3-NF-κB signaling, which, in turn, revealed HIF1α-dependent decreases the angiogenesis pathway in adipose tissue, including regulation of VEGF and TGFßR2 levels. In white adipose tissue, a set of lipogenesis-related genes, Srebp1, Fas, and Scd-1 were markedly downregulated after losartan intervention, as well as reduced LDs size and LD-associated proteins, perilipin family proteins (PLINs) compared with obese mice. Losartan abolished macrophage infiltration with upregulation of M2 and inhibition of M1 macrophage markers in obese mice. Our data suggest that losartan attenuated obese-induced fatty liver, linked to alleviating inflammation in adipose tissues and a shift in M1/M2 macrophage balance. Furthermore, losartan might improve mitochondria biogenesis by upregulating SIRT1, PGC1α, UCP1, and mRNA of Tfam, Cd137, Tmem26, Ucp1 expression in white adipose tissue compared with the obese group. Taken together, losartan may improve IR and adipose dysfunction by inhibiting lipotoxicity and HIF1α pathways.

RNA interference of mTOR gene delays molting process in Eriocheir sinensis.

mTOR is a typical and conserved serine/threonine protein kinase that regulates cell growth and metabolism of organisms. Molting is a fundamental biological process in Chinese mitten crab (Eriocheir sinensis) and is monitored by a series of genes and pathways. The structural and functional characteristics of EsmTOR was investigated to determine the role of mTOR in the molting process of. The intact CDS of EsmTOR is 7449 bp in length and encodes a polypeptide consisting of 2482 amino acids. EsmTOR was expressed in all eight tissues examined during the three molting stages (postmolt, intermolt andpremolt), with levels fluctuating significantly during the molting. RNA interference of EsmTOR significantly delayed molting, indicating that mTOR may be involved in the molting process of E. sinensis. Meanwhile, a substantial downregulation was observed for the expression of upstream genes involved in amino acid transport (EsSLC7A5 and EsVATB) and downstream genes promoting ribosomal protein synthesis (EsS6K1) in the mTOR signaling pathway, as well as typical molt-related genes (EsMIH and EsEcR) after EsmTOR RNAi treatment. In addition, EsRheb, a molecular marker for tissue growth, was also significantly down-regulated. This study suggests that EsmTOR plays a fundamental role in molting regulation through the SLC7A5-V-ATPase-mTORC1 gene network.

Influence of Femoral Version on the Outcomes of Hip Arthroscopic Surgery for Femoroacetabular Impingement or Labral Tears: A Systematic Review and Meta-analysis.

BACKGROUND: It remains controversial whether abnormal femoral version (FV) affects the outcomes of hip arthroscopic surgery for femoroacetabular impingement (FAI) or labral tears. PURPOSE: To review the outcomes of hip arthroscopic surgery for FAI or labral tears in patients with normal versus abnormal FV. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: Embase, PubMed, and the Cochrane Library were searched in July 2020 for studies reporting the outcomes after primary hip arthroscopic surgery for FAI or labral tears in patients with femoral retroversion (<5°), femoral anteversion (>20°), or normal FV (5°-20°). The primary outcome was the modified Harris Hip Score (mHHS), and secondary outcomes were the visual analog scale (VAS) for pain, Hip Outcome Score-Sport-Specific Subscale (HOS-SSS), Non-Arthritic Hip Score (NAHS), failure rate, and patient satisfaction. The difference in preoperative and postoperative scores (Δ) was also calculated when applicable. RESULTS: Included in this review were 5 studies with 822 patients who underwent hip arthroscopic surgery for FAI or labral tears; there were 166 patients with retroversion, 512 patients with normal version, and 144 patients with anteversion. Patients with retroversion and normal version had similar postoperative mHHS scores (mean difference [MD], 2.42 [95% confidence interval (CI), -3.42 to 8.26]; P = .42) and ΔmHHS scores (MD, -0.70 [96% CI, -8.56 to 7.15]; P = .86). Likewise, the patients with anteversion and normal version had similar postoperative mHHS scores (MD, -3.09 [95% CI, -7.66 to 1.48]; P = .18) and ΔmHHS scores (MD, -1.92 [95% CI, -6.18 to 2.34]; P = .38). Regarding secondary outcomes, patients with retroversion and anteversion had similar ΔNAHS scores, ΔHOS-SSS scores, ΔVAS scores, patient satisfaction, and failure rates to those with normal version, although a significant difference was found between the patients with retroversion and normal version regarding postoperative NAHS scores (MD, 5.96 [95% CI, 1.66-10.26]; P = .007) and postoperative HOS-SSS scores (MD, 7.32 [95% CI, 0.19-14.44]; P = .04). CONCLUSION: The results of this review indicated that abnormal FV did not significantly influence outcomes after hip arthroscopic surgery for FAI or labral tears.

Bone Marrow Stromal Cell-Derived Exosomes Promote Muscle Healing Following Contusion Through Macrophage Polarization.

Skeletal muscle contusion is among the most common injuries in traumatology and clinics of sports medicine. The injured muscle is vulnerable to re-injury owing to fibrosis formation. Given that the bone marrow stromal cell-derived exosomes (BMSC-Exos) displayed promising therapeutic effect for various tissues, we used BMSC-Exos to treat skeletal muscle contusion and investigated its effects on muscle healing. In this study, the in vivo model of skeletal muscle contusion was established by subjecting the tibialis anterior of young male mice to hit injury, and the in vitro inflammation model was established by lipopolysaccharide treatment on macrophages. Macrophage depletion model was built by intraperitoneal injection with clodronate-containing liposomes. Exosomes were isolated and purified from the supernatant of BMSCs using gradient centrifugation. Nanoparticle tracking analysis, transmission electron microscope, and western blot were used to identify the exosomes. HE stain, Masson stain, immunofluorescence, and biomechanical testing were carried out on the muscle tissue. In addition, enzyme-linked immunosorbent assay (ELISA) assays, real-time qPCR, flow cytometry, and PKH67 fluorescence trace were conducted in vitro. Intramuscular injection of BMSC-Exos to mice after muscle contusion alleviated inflammation level, reduced fibrosis size, promoted muscle regeneration, and improved biomechanical property. After macrophages depletion, the effects of BMSC-Exos were inhibited. In vitro, PKH-67 fluorescence was internalized into macrophages. BMSC-Exos promoted M2 macrophages polarization both in vivo and in vitro. At the same time, BMSC-Exos reduced the production of inflammatory cytokines under the inflammatory microenvironment and upregulated anti-inflammatory factors expression. In conclusion, BMSC-Exos attenuated muscle contusion injury and promoted muscle healing in mice by modifying the polarization status of macrophages and suppressing the inflammatory reaction.

PRICKLE3 linked to ATPase biogenesis manifested Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited eye disease. X-linked nuclear modifiers were proposed to modify the phenotypic manifestation of LHON-associated mitochondrial DNA (mtDNA) mutations. By whole-exome sequencing, we identified the X-linked LHON modifier (c.157C>T, p.Arg53Trp) in PRICKLE3 encoding a mitochondrial protein linked to biogenesis of ATPase in 3 Chinese families. All affected individuals carried both ND4 11778G>A and p.Arg53Trp mutations, while subjects bearing only a single mutation exhibited normal vision. The cells carrying the p.Arg53Trp mutation exhibited defective assembly, stability, and function of ATP synthase, verified by PRICKLE3-knockdown cells. Coimmunoprecipitation indicated the direct interaction of PRICKLE3 with ATP synthase via ATP8. Strikingly, cells bearing both p.Arg53Trp and m.11778G>A mutations displayed greater mitochondrial dysfunction than those carrying only a single mutation. This finding indicated that the p.Arg53Trp mutation acted in synergy with the m.11778G>A mutation and deteriorated mitochondrial dysfunctions necessary for the expression of LHON. Furthermore, we demonstrated that Prickle3-deficient mice exhibited pronounced ATPase deficiencies. Prickle3-knockout mice recapitulated LHON phenotypes with retinal deficiencies, including degeneration of retinal ganglion cells and abnormal vasculature. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between mtDNA mutations and X-linked nuclear modifiers.

Spontaneous bacterial peritonitis caused by Campylobacter Coli in cirrhotic patient: A rare case report (CARE-compliant).

INTRODUCTION: Spontaneous bacterial peritonitis (SBP) is a fatal infection in patients. It often happens in patients with cirrhosis, cancer or diabetes, and is caused mostly by Enterobacteriaceae. Here we report a rare case of SBP caused by Campylobacter Coli (C coli) infection, which was identified promptly by the matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and received adequate therapy sooner after. PATIENT CONCERNS: In the present study, we reported a 46-year-old male with alcoholic liver cirrhosis (Child-Pugh class C) and type 2 diabetes mellitus presented with a 1-day history of fever and abdominal pain. DIAGNOSIS: Based on the clinical examinations, the patient was diagnosed with SBP and the pathogen was quickly identified as C coli by the matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), a rare causative pathogen of SBP. INTERVENTIONS: The patient received a 10-day antibiotic treatment with Ciprofloxacin 400 mg every 12 hours, and recovered successfully. OUTCOMES: The patient had a successful treatment outcome. CONCLUSION: The study demonstrated a new possible infectious cause of SBP by C Coli, which was rarely seen in liver cirrhosis but mostly found in immunocompromised patients. Thus, it might raise an idea of microorganism screening of broader types that might also induce SBP for immunocompromised patients.

Interaction between particles and bubbles driven by ultrasound: Acoustic radiation force on an elastic particle immersed in the ideal fluid near a bubble.

A theoretical model is proposed to investigate the acoustic radiation force on the elastic particle for coupled particle-bubble system. Based on the sound scattering theory, an analytical expression of the force function is obtained for the particle in plane wave sound field. Numerical simulations are presented for elastic particle of stainless steel, steel or brass. The results reveal that the presence of bubbles can affect the feature of radiation force curves of particles. The force curve fluctuates, and negative force emerges in the small kR1 region for certain distance between the bubble and particle. There are more sharp peaks and dips in the curves because of the resonance of the elasticity of the system and the resonant peaks of the acoustic radiation force transfer to low frequencies when the size of elastic particle is increased. The approximate positive flat region is shortened because of the presence of bubble, which may help to optimize the size ranges of particle for acoustic screening. This study provides for improvement of the acoustic manipulation theoretical model.

Concomitant pulmonary sarcoidosis and HIV infection: A case report.

RATIONALE: Sarcoidosis is an immune-mediated systemic disease, and the increase in CD4+ T lymphocyte cells is considered as a key factor for the development of sarcoidosis. The acquired immune deficiency syndrome (AIDS) is well known as the impaired immune system and characterized by relative lack of CD4+ T lymphocytes. Thus, the coexistence of sarcoidosis and HIV infection has rarely been reported. PATIENT CONCERNS: A 65-year-old female patient was admitted to our respiratory ward complained of fatigue, chest distress, and a persistent dry cough for 2 months. DIAGNOSES: The chest computed tomography scan showed diffuse reticulonodular infiltrates and mediastinal and hilar lymphadenopathy. Fibreoptic bronchoscopy along with transbronchial biopsy and transbronchial needle aspiration was performed. The pathological findings revealed noncaseating granulomas, and the patient was found to be HIV-seropositive through enzyme-linked immunosorbent assay and confirmed as HIV by the centers for disease control and prevention. INTERVENTIONS: The patient was administered oral methylprednisolone 20 mg/day for pulmonary sarcoidosis and then referred to the hospital for infectious diseases receiving subsequent treatment for HIV. OUTCOMES: clinical symptoms relieved 3 months later after treatment. LESSONS: The coexistence of sarcoidosis and HIV infection is rare because of paradoxical roles of CD4-positive T cells in the pathogenesis of AIDS and sarcoidosis.

Mutation in NPPA causes atrial fibrillation by activating inflammation and cardiac fibrosis in a knock-in rat model.

Atrial fibrillation (AF) affects >30 million individuals worldwide. However, no genetic mutation from human patients with AF has been linked to inflammation. Here, we show that AF-associated human variant p.Ile138Thr in natriuretic peptide A (NPPA) encoding the atrial natriuretic peptide (ANP) causes inflammation, fibroblast activation, atrial fibrosis, and AF in knock-in (KI) rats. Variant p.Ile138Thr inhibits the interaction between ANP and its receptor natriuretic peptide receptor A and reduces intracellular cGMP levels. RNA sequencing and follow-up analyses showed that mutant ANP (mANP) activates multiple innate immunity pathways, including TNF-α, NF-κB, and IL-1ß signaling. mANP induces differentiation of cardiac fibroblasts (CFs) to myofibroblasts and promotes CF proliferation and fibrosis. These results suggest that NPPA variant p.Ile138Thr causes AF by activating TNF-α, NF-κB, and IL-1ß signaling, inflammation, and fibrosis. Multiple computational programs suggest that p.Ile138Thr is damaging or deleterious. Based on the 2015 American College of Medical Genetics and Genomics Standards and Guidelines, p.Ile138Thr can be classified as a likely pathogenic variant. Variant p.Ile138Thr was found only in Asian people in the Genome Aggregation Database and Exome Aggregation Consortium database at an averaged frequency of 0.026%. An estimated 1.15 million Asian people carry the variant and might be at risk of AF. The KI rats may provide an inflammation-based, genetic animal model for AF valuable for testing anti-inflammation or other therapies for AF.-Cheng, C., Liu, H., Tan, C., Tong, D., Zhao, Y., Liu, X., Si, W., Wang, L., Liang, L., Li, J., Wang, C., Chen, Q., Du, Y., Wang, Q. K., Ren, X. Mutation in NPPA causes atrial fibrillation by activating inflammation and cardiac fibrosis in a knock-in rat model.

The prevalence of human T-cell leukemia virus in blood donors in China.

BACKGROUND: China has not yet incorporated routine human T-lymphotropic virus (HTLV)-1/2 blood donor screening, even though HTLV has been reported in the southeastern coastal region. This study was conducted to investigate the prevalence of HTLV in five major regions across of China. METHODS: From January 2016 to December 2017, blood samples were collected in 20 blood centers located in different regions of China. These samples were screened for HTLV-1/2 antibodies using enzyme-linked immunosorbent assay (ELISA). If the test samples were reactive, the samples were confirmed with a western blot (WB) assay. If the results of WB were indeterminate, the donor was interviewed after a minimum lapse of 8 weeks. All follow-up samples from donors were tested for anti-HTLV-1/2 with ELISA and WB. RESULTS: There were 875,453 donor samples tested for anti-HTLV-1/2 by ELISA. In all, 365 samples tested negative, 22 samples tested positive by WB, and 14 samples with HTLV status undetermined due to being lost to follow-up. The prevalences were 11.09, 5.96, 3.16, 2.88 and 0.98 per 100,000 in Xiamen, Changsha, Beijing, Shenzhen, and Nanjing blood center, respectively. The prevalences were 0 per 100,000 for all 15 other blood centers. There was significant differences in the prevalence of HTLV in different regions of China (p = 0.0011). CONCLUSION: In China, HTLV-1 confirmed positive donors are mainly from southeastern coastal areas. It may be necessary to conduct HTLV screening in these areas to reduce the risk of transfusion-transmitted HTLV.

Isolation and functional validation of the CmLOX08 promoter associated with signalling molecule and abiotic stress responses in oriental melon, Cucumis melo var. makuwa Makino.

BACKGROUND: Lipoxygenases (LOXs) play significant roles in abiotic stress responses, and identification of LOX gene promoter function can make an important contribution to elucidating resistance mechanisms. Here, we cloned the CmLOX08 promoter of melon (Cucumis melo) and identified the main promoter regions regulating transcription in response to signalling molecules and abiotic stresses. RESULTS: The 2054-bp promoter region of CmLOX08 from melon leaves was cloned, and bioinformatic analysis revealed that it harbours numerous cis-regulatory elements associated with signalling molecules and abiotic stress. Five 5'-deletion fragments obtained from the CmLOX08 promoter-2054 (LP1), 1639 (LP2), 1284 (LP3), 1047 (LP4), and 418 bp (LP5)-were fused with a GUS reporter gene and used for tobacco transient assays. Deletion analysis revealed that in response to abscisic acid, salicylic acid, and hydrogen peroxide, the GUS activity of LP1 was significantly higher than that of the mock-treated control and LP2, indicating that the - 2054- to - 1639-bp region positively regulates expression induced by these signalling molecules. However, no deletion fragment GUS activity was induced by methyl jasmonate. In response to salt, drought, and wounding treatments, LP1, LP2, and LP4 promoted significantly higher GUS expression compared with the control. Among all deletion fragments, LP4 showed the highest GUS expression, indicating that - 1047 to - 1 bp is the major region regulating promoter activity and that the - 1047 to - 418-bp region positively regulates expression induced by salt, drought, and wounding, whereas the - 1284 to - 1047-bp region is a negative regulatory segment. Interestingly, although the GUS activity of LP1 and LP2 was not affected by temperature changes, that of LP3 was significantly induced by heat, indicating that the - 1284- to - 1-bp region is a core sequence responding to heat and the - 2054- to - 1284-bp region negatively regulates expression induced by heat. Similarly, the - 1047- to - 1-bp region is the main sequence responding to cold, whereas the - 2054- to - 1047-bp region negatively regulates expression induced by cold. CONCLUSIONS: We cloned the CmLOX08 promoter and demonstrated that it is a signalling molecule/stress-inducible promoter. Furthermore, we identified core and positive/negative regulatory regions responding to three signalling molecules and five abiotic stresses.

Physalin B induces G2/M cell cycle arrest and apoptosis in A549 human non-small-cell lung cancer cells by altering mitochondrial function.

Physalin B (PB) is one of the major constituents of Physalis alkekengi var. franchetii, a well-known Chinese traditional herb. In this study, we demonstrated for the first time that PB exhibits significant antiproliferative and apoptotic activity in A549 human lung cancer cells in a concentration-dependent and time-dependent manner. Flow cytometric analyses indicated that PB-induced G2/M arrest through down-regulation of cyclin B1 and cell division control protein cyclin-dependent kinase 1, and up-regulation of p21. The reduction in the level of cyclin B1/cyclin-dependent kinase 1 complex down-regulated oxidative phosphorylation multisubunit activity to reduce mitochondrial energetic homeostasis. Moreover, defects in mitochondrial ATP synthesis and mitochondrial membrane potential were found in PB-treated cell lines. These abnormalities led to an increase in intracellular superoxide and apoptosis. Thus, as an inhibitor of mitochondrial energetic homeostasis, PB demonstrates potent antitumor activities and may be developed as an alternative therapeutic agent against non-small-cell lung cancer.