Molecular and cellular role of variants of the promoter region of HAND1 gene in sporadic and isolated ventricular septal defect.

Ventricular septal defect (VSD) is the most common type of congenital heart disease. HAND1 gene plays a crucial role in the development of the heart, but the role of the variants in the HAND1 gene promoter region in patients with VSD has not been explored yet. From 588 participants (300 with isolated and sporadic VSD and 288 healthy controls), DNA was extracted from blood samples. Variants at the HAND1 gene promoter region were analyzed through Sanger sequencing. Subsequently, cell functional validation was conducted through cell experiments, including dual-luciferase reporter gene analysis, electrophoretic mobility shift analysis, and bioinformatics analysis was also conducted. The promoter region of HAND1 gene had a total of 9 identified variant sites. Among them, 4 variants were exclusively found in VSD patients, and 1 variant (g.3631A>C) was newly discovered. Cell functional experiments indicated that all four variants decreased the transcriptional activity of HAND1 gene promoter with three of them reached statistical significance (p < 0.05). Subsequent analysis using JASPAR (a transcription factor binding profile database) suggests that these variants may alter the binding sites of transcription factors, potentially contributing to the formation of VSD. Our study for the first time identified variants in the promoter region of HAND1 gene in Chinese patients with isolated and sporadic VSD. These variants significantly decreased the expression of HAND1 gene, impacting transcription factor binding sites, and thereby demonstrating pathogenicity. This study offers new insights into the role of HAND1 gene promoter region, contributing to a better understanding of the genetic basis of VSD formation.

Philadelphia chromosome-like acute lymphoblastic leukemia with concomitant rearrangements of CRLF2 and ABL1: a pediatric case report.

BACKGROUND: BCR::ABL1-like or Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) was first reported in 2009. Ph-like ALL is characterized by gene signature similar to Philadelphia chromosome ALL, but without BCR::ABL1 fusions. Molecularly, Ph-like ALL is divided into seven categories, with CRLF2 and ABL-class rearrangements being the two most common subtypes, exhibiting alterations in distinct downstream signaling cascades. CASE PRESENTATION: We report a rare case of pediatric Ph-like ALL with concomitant CRLF2 and ABL1 rearrangements. CRLF2 was fused with P2RY8, its most common fusion partner, whereas ABL1 was fused with MYO18B, a novel fusion partner that has not been previously reported. The 4-year-old female patient was treated using the national multicenter CCCG-ALL-2020 protocol with the addition of dasatinib at the end of induction when ABL1 rearrangement was confirmed by RNA-seq. Morphologically and molecularly, the patient remained in continuous remission until the last follow-up. To the best of our knowledge, this is the first case of Ph-like ALL harboring two distinct rearrangement categories. CONCLUSIONS: Our results identified that ABL1 rearrangement and CRLF2 rearrangement can coexist. The application of FISH, whole transcription sequencing, PCR can help us to have a more comprehensive understanding of ALL cytogenetics and molecular biology. Further studies are needed to explore the role of targeted therapies in such rare clinical scenarios.

A P1-like MYB transcription factor boosts biosynthesis and transport of C-glycosylated flavones in duckweed.

C-glycosylated flavones (CGFs) are the main flavonoids in duckweed (Lemna turionifera), known for their diverse pharmacological activities and nutritional values. However, the molecular mechanisms underlying flavonoid metabolism in duckweed remain poorly understood. This study identified a P1-Like R2R3-MYB transcription factor, LtP1L, as a crucial regulator of CGF biosynthesis and transport in L. turionifera. Over-expression of LtP1L led to a six-fold increase in CGF levels, whereas the CRISPR-mediated knockdown of LtP1L caused a drastic 74.3 % decrease in CGF contents compared with the wild type. LtP1L specifically activated the expression of genes encoding key enzymes involved in the biosynthesis of CGFs, including flavanone 3'-hydroxylases (F3'H), flavanone 2-hydroxylases (F2H), and C-glycosyltransferase (CGT). Meanwhile, LtP1L activated genes associated with phenylalanine and phenylpropanoid biosynthesis pathways, such as 3-deoxy-7-phosphoheptulonate synthase (DHS), phenylalanine ammonia-lyase (PAL), cinnamate 4-hydroxylase (C4H), and 4-coumarate: CoA ligase (4CL), redirecting carbon metabolic flux towards flavonoid pathway at the early stages of phenylalanine synthesis. In addition, LtP1L directly bound to a novel AC-like cis-element in the promoter of a tonoplast-localized ATP-binding cassette (ABC) transporter LtABCC4 and activated its expression. Furthermore, the preference of LtABCC4 for isoorientin over orientin during vacuolar transport was evidenced by the significant reduction of isoorientin compared to orientin in the Ltabcc4crispr lines. Altogether, LtP1L acts as a crucial transcriptional orchestrator in coordinating the biosynthesis and intracellular transport of CGFs in duckweed.

The Characteristics of Coronary Artery Lesions in COVID-19 Infected Patients With Coronary Artery Disease: An Optical Coherence Tomography Study.

COVID-19 may predispose patients to cardiac injuries but whether COVID-19 infection affects the morphological features of coronary plaques to potentially influence the outcome of patients with coronary artery disease (CAD) remains unknown. By using optical coherence tomography (OCT), this study compared the characteristics of coronary plaque in patients with CAD with/without COVID-19 infection. The 206 patients were divided into 2 groups. The COVID-19 group had 113 patients between December 7, 2022, and March 31, 2023, who received OCT assessment after China decided to lift the restriction on COVID-19 and had a history of COVID-19 infection. The non-COVID-19 group had 93 patients without COVID-19 infection who underwent OCT before December 7, 2022. The COVID-19 group demonstrated a higher incidence of plaque ruptures (53.1% vs 38.7%, p = 0.039), erosions (28.3% vs 11.8%, p = 0.004), fibrous (96.5% vs 89.2%, p = 0.041) and diffuse lesions (73.5% vs 50.5%, p <0.001) compared with the non-COVID-19 group, whereas non-COVID-19 group exhibited a higher frequency of cholesterol crystals (83.9% vs 70.8%, p = 0.027), deep calcifications (65.6% vs 51.3%, p = 0.039) and solitary lesions (57.0% vs 34.5%, p = 0.001). Kaplan-Meier survival analysis revealed a significantly lower major adverse cardiac events-free probability in the COVID-19 group (91.6% vs 95.5%, p = 0.006) than in the non-COVID-19 group. In conclusion, OCT demonstrated that COVID-19 infection is associated with coronary pathological changes such as more plaque ruptures, erosions, fibrosis, and diffuse lesions. Further, COVID-19 infection is associated with a higher propensity for acute coronary events and a higher risk of major adverse cardiac events in patients with CAD.

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In the context of rapid urbanization, metropolitan areas are facing the risk of supply-demand mismatches among ecosystem services. Investigating the patterns, relationships, and driving factors of multiple supply-demand risks is of great significance to support the efficient management of regional ecological risks. We quantified the single/comprehensive supply-demand risk rates of six ecosystem services in Wuhan Metropolitan Area at the township scale in 2000, 2010, and 2020. By applying the self-organizing feature map network and optimal parameter geo-detector, we identified supply-demand risks bundles of ecosystem services and influencing factors of comprehensive risks. The results showed significant spatial variations in the supply-demand risks of typical ecosystem services from 2000 to 2020. The supply-demand risk associated with grain production, water yield, carbon sequestration, and green space recreation increased, while soil conservation and water purification risks decreased. The comprehensive ecosystem services supply-demand risk increased from 0.41 to 0.45, indicating a 'core area increase and periphery decrease' trend. Throughout the study period, the area exhibited bundles of comprehensive extremely high-risk bundles (B1), comprehensive high-risk bundles (B2), water purification high-risk bundles (B3), and grain production-soil conservation risk bundles (B4). The transition of risk types from B3 to B2 and from B2 to B1 suggested an increase in the combination and intensity of supply-demand risk. Vegetation cover, nighttime light index, and population density were the main driving factors for spatial variations in comprehensive supply-demand risk. Ecologi-cal risk assessment based on ecosystem services supply-demand bundles could provide an effective and reliable way to regulate multiple regional risk issues.

Integration of C3H15-mediated transcriptional and post-transcriptional regulation confers plant thermotolerance in Arabidopsis.

Heat stress is an environmental factor that significantly threatens crop production worldwide. Nevertheless, the molecular mechanisms governing plant responses to heat stress are not fully understood. Plant zinc finger CCCH proteins have roles in stress responses as well as growth and development through protein-RNA, protein-DNA, and protein-protein interactions. Here, we reveal an integrated multi-level regulation of plant thermotolerance that is mediated by the CCCH protein C3H15 in Arabidopsis. Heat stress rapidly suppressed C3H15 transcription, which attenuated C3H15-inhibited expression of its target gene HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2), a central regulator of heat stress response (HSR), thereby activating HEAT SHOCK COGNATE 70 (HSC70.3) expression. The RING-type E3 ligase MED25-BINDING RING-H2 PROTEIN 2 (MBR2) was identified as an interacting partner of C3H15. The mbr2 mutant was susceptible to heat stress compared to wild-type plants, whereas plants overexpressing MBR2 showed increased heat tolerance. MBR2-dependent ubiquitination mediated the degradation of phosphorylated C3H15 protein in the cytoplasm, which was enhanced by heat stress. Consistently, heat sensitivities of C3H15 overexpression lines increased in MBR2 loss-of-function and decreased in MBR2 overexpression backgrounds. Heat stress-induced accumulation of HSC70.3 promoted MBR2-mediated degradation of C3H15 protein, implying that an auto-regulatory loop involving C3H15, HSFA2, and HSC70.3 regulates HSR. Heat stress also led to the accumulation of C3H15 in stress granules (SGs), a kind of cytoplasmic RNA granule. This study advances our understanding of the mechanisms plants use to respond to heat stress, which will facilitate technologies to improve thermotolerance in crops.

Scriptaid is a prospective agent for improving human asthenozoospermic sample quality and fertilization rate in vitro.

ABSTRACT: Male infertility is a global issue caused by poor sperm quality, particularly motility. Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology (ART) treatment. Scriptaid, with a novel human sperm motility-stimulating activity, has been investigated as a prospective agent for improving sperm quality and fertilization rate in ART. We evaluated the effects of Scriptaid on asthenozoospermic (AZS) semen, including its impact on motility stimulation and protective effects on cryopreservation and duration of motility, by computer-aided sperm analysis (CASA). Sperm quality improvement by Scriptaid was characterized by increased hyaluronan-binding activity, tyrosine phosphorylation, adenosine triphosphate (ATP) concentration, mitochondrial membrane potential, and an ameliorated AZS fertilization rate in clinical intracytoplasmic sperm injection (ICSI) experiments. Furthermore, our identification of active Scriptaid analogs and different metabolites induced by Scriptaid in spermatozoa lays a solid foundation for the future biomechanical exploration of sperm function. In summary, Scriptaid is a potential candidate for the treatment of male infertility in vitro as it improves sperm quality, prolongs sperm viability, and increases the fertilization rate.

Metabolomics Analysis Identifies Differential Metabolites as Biomarkers for Acute Myocardial Infarction.

Myocardial infarction (MI), including ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI), is still a leading cause of death worldwide. Metabolomics technology was used to explore differential metabolites (DMs) as potential biomarkers for early diagnosis of STEMI and NSTEMI. In the study, 2531 metabolites, including 1925 DMs, were discovered. In the selected 27 DMs, 14 were successfully verified in a new cohort, and the AUC values were all above 0.8. There were 10 in STEMI group, namely L-aspartic acid, L-acetylcarnitine, acetylglycine, decanoylcarnitine, hydroxyphenyllactic acid, ferulic acid, itaconic acid, lauroylcarnitine, myristoylcarnitine, and cis-4-hydroxy-D-proline, and 5 in NSTEMI group, namely L-aspartic acid, arachidonic acid, palmitoleic acid, D-aspartic acid, and palmitelaidic acid. These 14 DMs may be developed as biomarkers for the early diagnosis of MI with high sensitivity and specificity. These findings have particularly important clinical significance for NSTEMI patients because these patients have no typical ECG changes.

Anti-Hu antibody associated paraneoplastic neurological syndrome in a child with ganglioneuroblastoma: A rare case report and literature review.

RATIONALE: Paraneoplastic neurological syndrome with anti-Hu antibody (Hu-PNS) is a neurological disorder that occur in patients with malignancy. The syndrome has a wide range of presentations and can present before diagnosis of primary malignancy. Familiarity with these paraneoplastic neurological syndromes can help early recognition and take appropriate regimens. PATIENTS CONCERNS: Diagnosis and treatment of Hu-PNS. DIAGNOSES: This is retrospective study that analyzed the clinical data of this case. Through retrospective analysis and targeted antibody screening, serum anti-Hu antibody was detected. Subsequent spinal imaging revealed a mass in the paraspinal region, which was confirmed as ganglioneuroblastoma by pathologic examination. INTERVENTIONS: The child was treated with a course of intravenous immunoglobulin and radical surgical operation without chemotherapy. OUTCOMES: The neurological symptoms were gradually improved and no signs indicate disease progression or tumor recurrence. LESSONS: Hu-PNS has rarely been reported in children with ganglioneuroblastomas. They can mimic non-neoplastic processes, making detection and diagnosis difficult. Serum and/or cerebrospinal fluid onconeural antibody can strongly indicate occult cancers. Early detection of paraneoplastic neurological syndromes can help take appropriate regimens and improve prognosis.

INFLUENCES OF HEAT STRESS ON GLUTAMATE TRANSMISSION-DEPENDENT EXPRESSION LEVELS OF IL-1ß and IL-18 IN BV-2 MICROGLIAL CELLS.

ABSTRACT: Objective: This study aimed to explore the impact of heat stress (HS) on glutamate transmission-dependent expression levels of interleukin-1ß (IL-1ß) and IL-18 in BV-2 microglial cells. Methods: BV-2 microglial cells were cultured in vitro , with cells maintained at 37°C serving as the control. The HS group experienced incubation at 40°C for 1 h, followed by further culturing at 37°C for 6 or 12 h. The experimental group was preincubated with glutamate, the glutamate antagonist riluzole, or the mGluR5 agonist, 2-chloro-5-hydroxyphenylglycine (CHPG), before HS. Glutamate content in BV-2 culture supernatant was assessed using colorimetric assay. Moreover, mRNA expression levels of EAAT3 and/or mGluR5 in BV-2 cells were determined via quantitative polymerase chain reaction. Interleukins (IL-1ß and IL-18) in cell culture supernatant were measured using enzyme-linked immunosorbent assay. Western blot analysis was employed to assess protein levels of IL-1ß and IL-18 in BV-2 cells. Results: HS induced a significant release of glutamate and increased the expression levels of mGluR5 and EAAT3 in BV-2 cells. It also triggered the expression levels and release of proinflammatory factors, such as IL-1ß and IL-18, synergizing with the effects of glutamate treatment. Preincubation with both riluzole and CHPG significantly reduced HS-induced glutamate release and mitigated the increased expression levels and release of IL-1ß and IL-18 induced by HS. Conclusion: The findings confirmed that microglia could be involved in HS primarily through glutamate metabolisms, influencing the expression levels and release of IL-1ß and IL-18.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

Synergistic nucleation regulation using 4,4',4''-tris(carbazol-9-yl)-triphenylamine and moisture for stably air-processed high-performance perovskite photodetectors.

Perovskite photodetectors (PPDs) offer a promising solution with low cost and high responsivity, addressing the limitations of traditional inorganic photodetectors. However, there is still room for improvement in terms of the dark current and stability of air-processed PPDs. In this study, 4,4',4''-tris(carbazol-9-yl)-triphenylamine (TCTA) was utilized as a nucleation agent to enhance the quality of perovskite films. The synergistic effect of TCTA and moisture promotes rapid nucleation of PbI2-PbCl2, resulting in an increased nucleation rate and the elimination of pinholes in the film. By employing additive engineering, we obtained a PbI2-PbCl2 layer with high coverage, leading to a low density of traps in the corresponding perovskite film. Consequently, the modified PPD exhibits a remarkable reduction in dark current density by over one order of magnitude, reaching 2.4 × 10-10 A cm-2 at -10 mV, along with a large linear dynamic range (LDR) of 183 dB. Furthermore, the resulting PPD demonstrates remarkable stability, retaining 90% of the initial external quantum efficiency (EQE) value even after continuous operation for over 3200 hours. Owing to a fast response time in the nanosecond range, the PPD could convert modulated light signals into electrical signals at a speed of 588 Kbit s-1, highlighting the great potential in the field of optical communication.

Cardiotoxicity induced by fluoropyrimidine drugs in the treatment of gastrointestinal tumors.

In this editorial, we review the article published in World J Gastrointest Oncol 2019, 11: 1031-1042. We specifically focus on the occurrence, clinical characteristics, and risk factors of fluoropyrimidine drug-related cardiotoxicity in patients with gastrointestinal tumors. Despite significant advancements in diagnostic and therapeutic techniques that have reduced mortality rates associated with digestive system tumors, the incidence and mortality rates of treatment-related cardiotoxicity have been increasing, severely impacting the survival and prognosis of cancer patients. Fluoropyrimidine drugs are widely used as antimetabolites in the treatment of malignant tumors, including gastrointestinal tumors, and they represent the second largest class of drugs associated with cardiotoxicity. However, there is often a lack of awareness or understanding regarding their cardiotoxic effects and associated risks.

MsHDZ23, a Novel Miscanthus HD-ZIP Transcription Factor, Participates in Tolerance to Multiple Abiotic Stresses.

The homeodomain-leucine zipper (HD-ZIP) transcription factors, representing one of the largest plant-specific superfamilies, play important roles in the response to various abiotic stresses. However, the functional roles of HD-ZIPs in abiotic stress tolerance and the underlying mechanisms remain relatively limited in Miscanthus sinensis. In this study, we isolated an HD-ZIP TF gene, MsHDZ23, from Miscanthus and ectopically expressed it in Arabidopsis. Transcriptome and promoter analyses revealed that MsHDZ23 responded to salt, alkali, and drought treatments. The overexpression (OE) of MsHDZ23 in Arabidopsis conferred higher tolerance to salt and alkali stresses compared to wild-type (WT) plants. Moreover, MsHDZ23 was able to restore the hb7 mutant, the ortholog of MsHDZ23 in Arabidopsis, to the WT phenotype. Furthermore, MsHDZ23-OE lines exhibited significantly enhanced drought stress tolerance, as evidenced by higher survival rates and lower water loss rates compared to WT. The improved drought tolerance may be attributed to the significantly smaller stomatal aperture in MsHDZ23-OE lines compared to WT. Furthermore, the accumulation of the malondialdehyde (MDA) under abiotic stresses was significantly decreased, accompanied by dramatically enhanced activities in several antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in the transgenic plants. Collectively, these results demonstrate that MsHDZ23 functions as a multifunctional transcription factor in enhancing plant resistance to abiotic stresses.

Effective Treatment of Anlotinib Combined With Chemotherapy in Children With Desmoplastic Small Round Cell Tumor: A Case Series in a Single-center and Literature Review.

INTRODUCTION: Desmoplastic small round cell tumor (DSRCT) is a highly aggressive primitive sarcoma with a 5-year survival rate estimated at only 15% to 30%. Although few curative treatment options exist, patients are most often treated with a combination of aggressive chemotherapy, radiation, and surgery. Targeted therapy inhibitors of platelet-derived growth factor A, insulin-like growth factor receptor 1, and vascular endothelial growth factor receptor-2, which are almost uniformly overexpressed in DSRCT, have largely failed in clinical trials. Anlotinib is a multitarget receptor tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor α/ß, c-Kit, and Met. In this study, we presented 3 cases of DSRCT treated effectively with anlotinib combined with chemotherapy. CASE PRESENTATION: Three children DSRCT patients were enrolled from September 2020 to December 2021 and monitored until August 30, 2022. The clinical data were prospectively studied. The peritoneal cancer index classified all 3 patients as stage IV. After surgery, all 3 patients received anlotinib in combination with chemotherapy and reacted to the medication. For all 3 patients, clinical symptoms were substantially eased, and the size of the masses was reduced. Patient 1 and patient 3's progression-free survival had been extended, and anlotinib was continued as a maintenance medication in the 2 patients who were in good health at the end of the follow-up. Patient 2 died of postoperative complications 1 month after second-stage surgery. The main side effects of anlotinib were fatigue and hypertension. However, its toxicity was controllable and tolerable in children patients. CONCLUSIONS: This is the first report that anlotinib is effective in children with DSRCT. This report may provide an additional option for the treatment of metastatic DSRCT.

Variants of the promoter of MYH6 gene in congenital isolated and sporadic patent ductus arteriosus: case-control study and cellular functional analyses.

Patent ductus arteriosus (PDA) is a common form of congenital heart disease. The MYH6 gene has important effects on cardiovascular growth and development, but the effect of variants in the MYH6 gene promoter on ductus arteriosus is unknown. DNA was extracted from blood samples of 721 subjects (428 patients with isolated and sporadic PDA and 293 healthy controls) and analyzed by sequencing for MYH6 gene promoter region variants. Cellular function experiments with three cell lines (HEK-293, HL-1, and H9C2 cells) and bioinformatics analyses were performed to verify their effects on gene expression. In the MYH6 gene promoter, 11 variants were identified. Four variants were found only in patients with PDA and 2 of them (g.3434G>C and g.4524C>T) were novel. Electrophoretic mobility shift assay showed that the transcription factors bound by the promoter variants were significantly altered in comparison to the wild-type in all three cell lines. Dual luciferase reporter showed that all the 4 variants reduced the transcriptional activity of the MYH6 gene promoter (P < 0.05). Prediction of transcription factors bound by the variants indicated that these variants alter the transcription factor binding sites. These pathological alterations most likely affect the contraction of the smooth muscle of ductus arteriosus, leading to PDA. This study is the first to focus on variants at the promoter region of the MYH6 gene in PDA patients with cellular function tests. Therefore, this study provides new insights to understand the genetic basis and facilitates further studies on the mechanism of PDA formation.

A novel porous titanium with engineered surface for bone defect repair in load-bearing position.

Porous titanium exhibits low elastic modulus and porous structure is thought to be a promising implant in bone defect repair. However, the bioinert and low mechanical strength of porous titanium have limited its clinical application, especially in load-bearing bone defect repair. Our previous study has reported an infiltration casting and acid corrosion (IC-AC) method to fabricate a novel porous titanium (pTi) with 40% porosity and 0.4 mm pore diameter, which exerts mechanical property matching with cortical bone and interconnected channels. In this study, we introduced a nanoporous coating and incorporated an osteogenic element strontium (Sr) on the surface of porous titanium (named as Sr-micro arch oxidation [MAO]) to improve the osteogenic ability of the pTi by MAO. Better biocompatibility of Sr-MAO was verified by cell adhesion experiment and cell counting kit-8 (CCK-8) test. The in vitro osteogenic-related tests such as immunofluorescence staining, alkaline phosphatase staining and real-time polymerase chain reaction (RT-PCR) demonstrated better osteogenic ability of Sr-MAO. Femoral bone defect repair model was employed to evaluate the osseointegration of samples in vivo. Results of micro-CT scanning, sequential fluorochrome labeling and Van Gieson staining suggested that Sr-MAO showed better in vivo osteogenic ability than other groups. Taking results of both in vitro and in vivo experiment together, this study indicated the Sr-MAO porous titanium could be a promising implant load-bearing bone defect.

Progress in mechanism-based diagnosis and treatment of tuberculosis comorbid with tumor.

Tuberculosis (TB) and tumor, with similarities in immune response and pathogenesis, are diseases that are prone to produce autoimmune stress response to the host immune system. With a symbiotic relationship between the two, TB can facilitate the occurrence and development of tumors, while tumor causes TB reactivation. In this review, we systematically sorted out the incidence trends and influencing factors of TB and tumor, focusing on the potential pathogenesis of TB and tumor, to provide a pathway for the co-pathogenesis of TB comorbid with tumor (TCWT). Based on this, we summarized the latest progress in the diagnosis and treatment of TCWT, and provided ideas for further exploration of clinical trials and new drug development of TCWT.

Lily (Lilium spp.) LhERF4 negatively affects anthocyanin biosynthesis by suppressing LhMYBSPLATTER transcription.

Anthocyanins are among the main pigments involved in the colouration of Asiatic hybrid lily (Lilium spp.). Ethylene, a plant ripening hormone, plays an important role in promoting plant maturation and anthocyanin biosynthesis. However, whether and how ethylene regulates anthocyanin biosynthesis in lily tepals have not been characterized. Using yeast one-hybrid screening, we previously identified an APETALA2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) named LhERF4 as a potential inhibitor of LhMYBSPLATTER-mediated negative regulation of anthocyanin biosynthesis in lily. Here, transcript and protein analysis of LhERF4, a transcriptional repressor, revealed that LhERF4 directly binds to the promoter of LhMYBSPLATTER. In addition, overexpression of LhERF4 in lily tepals negatively regulates the expression of key structural genes and the total anthocyanin content by suppressing the LhMYBSPLATTER gene. Moreover, the LhERF4 gene inhibits anthocyanin biosynthesis in response to ethylene, affecting anthocyanin accumulation and pigmentation in lily tepals. Collectively, our findings will advance and elucidate a novel regulatory network of anthocyanin biosynthesis in lily, and this research provides new insight into colouration regulation.