An Overview of Miami CDEIPI and a Showcase of Team Science and Cutting-Edge Research Driven by Students.

BACKGROUND: The Miami-CFAR Diversity, Equity & Inclusion Pathway Initiative (Miami CDEIPI) is designed to promote a diverse scientific workforce that reflects the communities at the highest risk of HIV in South Florida. SETTING AND METHODS: The focus of the Miami CDEIPI is to help train the next generation of Underrepresented Minorities (URM) and Black, Indigenous, People of Color (BIPOC) in HIV/AIDS-related research through a team science experience. The Miami CDEIPI objectives are to facilitate the interaction of URM/BIPOC students with the network of CFAR-affiliated investigators and to enable these students to access the cutting-edge technologies at the Miami-CFAR and the Sylvester Comprehensive Cancer Center and other resources at the University of Miami. RESULTS: Five URM/BIPOC students supported by the program in year 1 have been carrying out projects in collaboration with mentors at their parent institution and Miami-CFAR investigators. The students used the state-of-the-art laboratories and core facilities. They began their research with a proposal designed to integrate the cutting-edge technologies now available to them. Their training included participation in Miami-CFAR-sponsored activities such as seminars, an annual conference, and a national HIV workshop. Candidates in the Miami CDEIPI are in the process of developing their research proposals, integrating cutting-edge technologies into their doctoral dissertation research. Their projects are now in the completion phase. CONCLUSIONS: The Miami CDEIPI focuses its resources on one of the conspicuous gaps in the career paths of URM/BIPOC researchers-the dearth of leading URM/BIPOC scientists in the field. The Miami CDEIPI provides a professional network that supports the participation of URM/BIPOC trainees in innovative research and career skill training.

The Efficacy and Safety of Xinjia Xuanbai Chengqi Granules in Acute Exacerbation of COPD: A Multicentre, Randomised, Double-Blind, Controlled Trial.

Purpose: The study aimed to explore the efficacy and safety of Xinjia Xuanbai Chengqi granules (XJXBCQ) combined with conventional medicine in the treatment of acute exacerbation of chronic pulmonary disease (AECOPD). Patients and Methods. This multicentre, double-blind, parallel, placebo-controlled, randomised clinical trial conducted in China from January 2019 to February 2021 recruited 330 participants who were allocated into three groups. All participants underwent conventional basic treatment with oxygen therapy, antibiotics, and a bronchodilator. Besides, group A received XJXBCQ granules and budesonide suspension for inhalation; group B received XJXBCQ granules and half dosage of budesonide suspension; and group C received budesonide suspension and a placebo. All therapies lasted for 5 days, and participants were followed up for 30 days after discharge. The primary outcomes were efficacy, traditional Chinese medicine (TCM) syndrome score, and clinical symptom score. Secondary outcomes included the blood gas analysis, serum inflammatory markers, adverse events, mortality, theoretical discharge time, actual hospitalisation time, proportion of patients requiring invasive mechanical ventilation, proportion of patients transferred to an intensive care unit (ICU), and readmission rate within 30 days after discharge. Results: XJXBCQ adjunct with conventional treatment could significantly improve the total efficacy (P < 0.05). Meanwhile, group A showed significantly better results than group C in the TCM syndrome score, phlegm score, and Wexner constipation score (P < 0.05). For modified British medical research council (mMRC), on day 3 (-0.17, 95% confidence interval [CI]: -0.33--0.01) and day 4 (-0.20, 95% CI: -0.39--0.02), group A performed statistically better than group C. No significant differences in other secondary outcomes were detected. Conclusion: XJXBCQ is beneficial and safe for AECOPD treatment and could be considered an adjunctive therapy for promoting the relief of clinical symptoms. This trial is registered with ChiCTR1800016915.

A pair of non-Mendelian genes at the Ga2 locus confer unilateral cross-incompatibility in maize.

Maize unilateral cross-incompatibility (UCI) that causes non-Mendelian segregation ratios has been documented for more than a century. Ga1, Ga2, and Tcb1 are three major UCI systems, described but not fully understood. Here, we report comprehensive genetic studies on the Ga2 locus and map-based cloning of the tightly linked male determinant ZmGa2P and female determinant ZmGa2F that govern pollen-silk compatibility among different maize genotypes. Both determinants encode putative pectin methylesterases (PME). A significantly higher degree of methyl esterification is detected in the apical region of pollen tubes growing in incompatible silks. No direct interaction between ZmGa2P and ZmGa2F is detected in the yeast two-hybrid system implying a distinct mechanism from that of self-incompatibility (SI). We also demonstrate the feasibility of Ga2 as a reproductive barrier in commercial breeding programs and stacking Ga2 with Ga1 could strengthen the UCI market potentials.

Treatment with JianPiYiFei II granules for patients with moderate to very severe chronic obstructive pulmonary disease: A 52-week randomised, double-blinded, placebo-controlled, multicentre trial.

BACKGROUND: Complementary and alternative therapy is widely used to treat chronic obstructive pulmonary disease (COPD). A Chinese herbal medicine, JianPiYiFei (JPYF) II granules, have been shown to improve COPD patients' quality of life, however long-term effectiveness has not been examined. PURPOSE: To investigate whether long-term treatment with JPYF II granules is effective and safe for patients with stable, moderate to very severe COPD. STUDY DESIGN AND METHODS: A multicentre, randomised, double-blinded, placebo-controlled trial was conducted. Eligible participants from six hospitals were randomly assigned 1:1 to receive either JPYF II granules or placebo for 52 weeks. The primary outcome was the change in St. George's Respiratory Questionnaire (SGRQ) score during treatment. Secondary outcomes included the frequency of acute exacerbations during treatment, COPD Assessment Test (CAT), 6-minute walking test (6MWT), lung function, body mass index, airflow obstruction, dyspnoea, exercise capacity (BODE) index, and peripheral capillary oxygen saturation (SpO2) at the end of treatment. RESULTS: A total of 276 patients (138 in each group) were included in the analysis. JPYF II granules led to a significantly greater reduction in SGRQ score (-7.33 points, 95% CI -10.59 to -4.07; p < 0.0001) which reflects improved quality of life. JPYF II granules improved CAT (-3.49 points, 95% CI -5.12 to -1.86; p < 0.0001) and 6MWT (45.61 metres, 95% CI 20.26 to 70.95; p = 0.0005), compared with placebo. Acute exacerbations were less frequent with JPYF II granules than with placebo (0.87 vs. 1.34 events per patient; p = 0.0043). There were no significant differences between the groups in lung function, BODE index and SpO2. JPYF II granules were well tolerated and no significant adverse effects were noted. CONCLUSIONS: Long-term treatment with JPYF II granules is effective in moderate to very severe COPD, improving quality of life and exercise capacity, decreasing the risk of acute exacerbation, and relieving symptoms.

Quanzhenyiqitang Reverses LPS-Induced Inflammation via Inhibiting PYK2/p38MAPK/HDAC2/CK2 Signaling Pathway in Rat Alveolar Macrophage.

Chronic obstructive pulmonary disease (COPD) is a common chronic pulmonary disease with multiple etiologies and pathological changes. PYK2 expression is significantly increased in lipopolysaccharide-induced lung injury, but it mediates chronic lung inflammation. The mechanism of its occurrence remains unclear. Quanzhenyiqitang is often used in clinical treatment of COPD, so this study explored the mechanism of its treatment of lipopolysaccharide-induced lung injury. In this study, transfection, flow cytometry, QRT-PCR, and Western blotting methods were used to study the mechanism of Quanzhenyiqitang lipopolysaccharide-induced lung injury. The results showed that the mechanism of occurrence remains unclear. Our novel observations imply that the PYK2/p38MAPK/HDAC2/CK2 pathway is one of the fundamental underlying mechanisms that mediate the pathogenic progression of COPD, and Quanzhenyiqitang may be the therapeutic drug to prevent chronic inflammation and delay the progression of COPD by inhibiting PYK2 signaling pathways.

Torrefaction, temperature, and heating rate dependencies of pyrolysis of coffee grounds: Its performances, bio-oils, and emissions.

The torrefaction pretreatment is of great significance to the efficient conversion of biomass residues into bioenergy. In this study, the effects of the three torrefaction temperatures (200, 250, and 300 °C) on the pyrolysis performance and products of coffee grounds (CG) were quantified. The torrefaction treatment increased the initial devolatilization and maximum peak temperatures of the CG pyrolysis. Activation energy of CG250 was lower than that of CG and more conducive to the pyrolysis. Torrefaction altered the distributions of the pyrolytic products and promoted the generation of C=C. Torrefaction changed the composition ratio of the pyrolytic bio-oils although cyanoacetic acid and 2-butene still dominated the bio-oils. The joint optimization pointed to pyrolysis temperature > 600 °C and torrefaction temperature ≤ 270 °C as the optimal conditions. Our experimental results also verified that torrefaction of CG may be more suitable at 200 and 250 °C than 300 °C.

A PECTIN METHYLESTERASE gene at the maize Ga1 locus confers male function in unilateral cross-incompatibility.

Unilateral cross-incompatibility (UCI) is a unidirectional inter/intra-population reproductive barrier when both parents are self-compatible. Maize Gametophyte factor1 (Ga1) is an intraspecific UCI system and has been utilized in breeding. However, the mechanism underlying maize UCI specificity has remained mysterious for decades. Here, we report the cloning of ZmGa1P, a pollen-expressed PECTIN METHYLESTERASE (PME) gene at the Ga1 locus that can confer the male function in the maize UCI system. Homozygous transgenic plants expressing ZmGa1P in a ga1 background can fertilize Ga1-S plants and can be fertilized by pollen of ga1 plants. ZmGa1P protein is predominantly localized to the apex of growing pollen tubes and may interact with another pollen-specific PME protein, ZmPME10-1, to maintain the state of pectin methylesterification required for pollen tube growth in Ga1-S silks. Our study discloses a PME-mediated UCI mechanism and provides a tool to manipulate hybrid breeding.

Transcriptome Analysis Provides Insight into the Molecular Mechanisms Underlying gametophyte factor 2-Mediated Cross-Incompatibility in Maize.

In maize (Zea mays L.), unilateral cross-incompatibility (UCI) is controlled by Gametophyte factors (Ga), including Ga1, Ga2, and Tcb1; however, the molecular mechanisms underpinning this process remain unexplored. Here, we report the pollination phenotype of an inbred line, 511L, which carries a near-dominant Ga2-S allele. We performed a high-throughput RNA sequencing (RNA-Seq) analysis of the compatible and incompatible crosses between 511L and B73, to identify the transcriptomic differences associated with Ga2-mediated UCI. An in vivo kinetics analysis revealed that the growth of non-self pollen tubes was blocked at the early stages after pollination in 511L, maintaining the UCI barrier in Ga2. In total, 25,759 genes were expressed, of which, 2063 differentially expressed genes (DEGs) were induced by pollination (G_GG, G_GB, B_BB, B_BG). A gene ontology (GO) enrichment analysis revealed that these genes were specifically enriched in functions involved in cell wall strength and pectic product modification. Moreover, 1839, 4382, and 5041 genes were detected to differentially express under same pollination treatments, including B_G, BG_GG, and BB_GB, respectively. A total of 1467 DEGs were constitutively expressed between the two inbred lines following pollination treatments, which were enriched in metabolic processes, flavonoid biosynthesis, cysteine biosynthesis, and vacuole functions. Furthermore, we confirmed 14 DEGs related to cell wall modification and stress by qRT-PCR, which might be involved in Ga2-S-mediated UCI. Our results provide a comprehensive foundation for the molecular mechanisms involved in silks of UCI mediated by Ga2-S.

Downregulated SOCS1 expression activates the JAK1/STAT1 pathway and promotes polarization of macrophages into M1 type.

Macrophage polarization is flexible, and involves in different signaling pathways and various transcription factors. Suppressor of cytokine signaling (SOCS) is an important inhibitor of cytokine signaling pathways and also a key physiological regulator for natural and acquired immunity systems. Following transfection of SOCS1 short hairpin (sh)RNA into mouse macrophage cells, reverse transcription­quantitative polymerase chain reaction demonstrated that the mRNA levels of Janus kinase (JAK)1 and signal transducer and activator of transcription (STAT)1 increased significantly. In addition, western blotting indicated that JAK1, STAT1 and p­STAT1 expression was significantly enhanced. Fludarabine can inhibit phosphorylation of STAT1 and SOCS1 expression. When fludarabine was added and SOCS1 shRNA was transfected, the inhibition of fludarabine was weakened, and p­STAT1 expression was upregulated. Flow cytometry detection indicated that, following the downregulation of SOCS1 expression, M1­type cells significantly increased, but the proportion of M2­type cells did not change significantly. Fludarabine can reduce the effect of SOCS1 shRNA on promoting M1­type cell polarization, and macrophages can polarize into both M1 and M2 phenotypes. Further ELISA results presented that, when downregulating SOCS1 expression, interleukin (IL)­4 and IL­10 expression was both downregulated, and tumor necrosis factor (TNF)­α and interferon (IFN)­Î³ expression was significantly upregulated. When adding fludarabine or injecting with the traditional Chinese medicine Xuebijing, IL­4 and IL­10 expression was both significantly upregulated, and TNF­α and IFN­Î³ expression was significantly downregulated. When adding fludarabine and downregulating SOCS1, IL­4, IL­10, TNF­α and IFN­Î³ expression presented no significant changes. The above results indicated that, when SOCS1 expression is downregulated, it will activate the JAK1/STAT1 pathway, and thereby promote the polarization of macrophages into M1 type. The findings are of great importance for understanding occurrence, development and treatment of various immune­related diseases.

miR-646 is a key negative regulator of EGFR pathway in lung cancer.

BACKGROUND: As one of the leading cause of cancer-related deaths in the worldwide, lung cancer needs to be understood better. Nowadays, increasing point mutations of specific oncogenes are biomarkers used to predict the therapeutic effect of targeted therapy and lung cancer has entered the age of individual treatment. At present, many relevant researchers have suggested that EGFR is a biomarker used to predict the therapeutic effect of targeted therapy. A large number of evidence indicates that EGFR/Akt pathway plays important role in cancer growth and metastasis. AIM OF THE STUDY: In this paper, we found EGFR was a target of miR-646. RESULTS: Overexpression of miR-646 not only downregulated EGFR/Akt pathway, but also inhibited lung cancer cell proliferation and metastasis. At the same time, miR-646 was a prognosis factor for overall survival. CONCLUSION: Our finding could provide new insights into the molecular therapeutic of lung cancer.

Different lasers in the treatment of benign prostatic hyperplasia: a network meta-analysis.

All available surgical treatments for benign prostatic hyperplasia (BPH) have their individual advantages or disadvantages. However, the lack of head-to-head studies comparing different surgeries makes it unavailable to conduct direct analysis. To compare the efficacy and safety among different lasers and transurethral resection of prostate (TURP) for BPH, randomized controlled trials were searched in MEDLINE, EMBASE, Cochrane library, WHO International Clinical Trial Registration Platform, and Clinical Trial.gov by 2015.5; and the effectiveness-, perioperation- and complication-related outcomes were assessed by network meta-analysis. 36 studies involving 3831 patients were included. Holmium laser through resection and enucleation had the best efficacy in maximum flow rate. Thulium laser through vapo-resection was superior in improving international prostate symptom score and holmium laser through enucleation was the best for post-voiding residual volume improvement. Diode laser through vaporization was the rapidest in removing postoperative indwelling catheter, while TURP was the longest. TURP required the longest hospitalization and thulium laser through vapo-resection was relatively shorter. Holmium and thulium lasers seem to be relatively better in surgical efficacy and safety, so that these two lasers might be preferred in selection of optimal laser surgery. Actually, more large-scale and high quality head-to-head RCTs are suggested to validate the conclusions.

Green tea epigallocatechin-3-gallate alleviates Porphyromonas gingivalis-induced periodontitis in mice.

Porphyromonas gingivalis causes inflammation, and leads to the periodontitis in gingival tissue damage and bone resorption. Epigallocatechin-3-gallate (EGCG) is a major polyphenol extract from green tea with plenty of pharmacological functions. The aim of this study was to determine whether continuous oral intake of EGCG would alleviate P. gingivalis-induced periodontitis. Eight-week BALB/c mice were administered with EGCG (0.02%) or vehicle in drinking water. They were fed normal food and orally infected with P. gingivalis every 2days, up to a total of 20 times, and then sacrificed at 15weeks of age. The P. gingivalis-challenged group markedly increased alveolar bone resorption of the maxillae in BALB/c mice by Micro-CT detection, and administration of EGCG resulted in a significant reduction in bone loss. Inflammation cytokine antibody array and enzyme linked immunosorbent assay revealed that some inflammatory mediators in serum were increased by P. gingivalis infection, but were lowered after EGCG treatment. High positive areas of IL-17 and IL-1ß in the gingival tissue were observed in the P. gingivalis-challenged mice, and were reduced by EGCG treatment. Real-time polymerase chain reaction (PCR) analyses also showed the expressions of IL-1ß, IL-6, IL-17, IL-23, TNF-α and other mediators in gingival tissue were higher in P. gingivalis-challenged mice, and were down-regulated with EGCG treatment, except IL-23. Our results suggest that EGCG, as a natural healthy substance, probably alleviates P. gingivalis-induced periodontitis by anti-inflammatory effect.

Maternally transmitted aminoglycoside-induced and non-syndromic hearing loss caused by the 1494C > T mutation in the mitochondrial 12S rRNA gene in two Chinese families.

OBJECTIVE: To explore the molecular genetic characterization of two Chinese families with aminoglycoside-induced and non-syndromic hearing loss (NSHL). DESIGN: Clinical evaluations, sequence analysis of mitochondrial DNA (mtDNA) as well as two nuclear genes TRMU and MTO1 encoding mitochondrial proteins. STUDY SAMPLE: Two Chinese families with aminoglycoside-induced and NSHL. RESULTS: Clinical evaluations revealed incomplete penetrance (28.6% vs. 40.0%) and variable phenotype of hearing losses between two families. When the effect of aminoglycosides was excluded, the penetrances were both 0%. Sequence analysis of mitochondrial genomes showed a homoplasmic 1494C > T mutation in the12S rRNA gene (MT-RNR1) in all maternal relatives, as well as distinct sets of mtDNA polymorphism belonging to Eastern Asian haplogroups D4j and D5a2, respectively. However, none of these mtDNA variants was highly evolutionarily conserved and implicated to have functional significance. No mutations were identified in either TRMU or MTO1 gene. CONCLUSIONS: Mitochondrial 1494C> T mutation is the molecular basis responsible for the NSHL of two families, and the use of aminoglycoside antibiotics can worsen the hearing of the mutation carriers. Our results indicate the importance of a systematic screening for the mitochondrial 1494C > T mutation in Chinese subjects in the prevention of aminoglycoside-induced and non-syndromic hearing loss.

[Analysis of urinary storage symptoms following transurethral resection of the prostate].

OBJECTIVE: To explore the lower urinary tract symptoms (LUTS), especially those in the urinary storage phase, following transurethral resection of the prostate (TURP), and to improve the postoperative management and patients' quality of life after TURP. METHODS: A total of 86 patients with benign prostate hyperplasia (BPH) underwent TURP, and were interviewed on urinary symptoms at 1, 3, 7, 15 and 30 days after removal of the catheter. The patients were divided into two groups according to whether they had preoperative detrusor instability and/or compliance of the bladder (Group A) or not (Group B), and observed for the changes in IPSS scores and urinary storage symptoms after removal of the catheter. RESULTS: Complete follow-ups were achieved in 71 cases, 28 with detrusor instability and/or compliance of the bladder and the other 43 without. Their IPSS scores on the 1st, 3rd, 7th, 15th and 30th day after removal of the catheter were 8.1 +/- 2.5, 7.2 +/- 3.1, 6.3 +/- 3.8, 5.3 +/- 4.2 and 2.4 +/- 3.4, respectively, with statistically significant differences between the 7th and the 1st as well as the 30th and the 15th day (P < 0.05), but not between the 1st and the3rd nor the 15th and the 7th day (P > 0.05). On the 1st day, the cardinal symptoms in the urinary storage phase were urinary frequency, urgency and incontinence; the scores on IPSS and urinary storage symptoms were 10.4 +/- 3.3 and 9.3 +/- 3.8 in Group A and 6.2 +/- 2.8 and 5.2 +/- 2.7 in Group B, with significant differences between the two groups (P < 0.05). After treatment with tolterodine and alpha-adrenoreceptor inhibitor, neither IPSS scores nor the scores on urinary storage symptoms showed any significant differences between Groups A and B on the 15th and 30th day (P > 0.05). CONCLUSION: The lower urinary tract symptoms following TURP, especially those in the urinary storage phase, are correlated with preoperative bladder function, and getting improved gradually after surgery.

[Andrographolide drop-pill in treatment of acute upper respiratory tract infection with external wind-heat syndrome: a multicenter and randomized controlled trial].

OBJECTIVE: To evaluate the safety and efficacy of andrographolide drop-pill in treatment of acute upper respiratory tract infection with external wind-heat syndrome. METHODS: A multicenter, randomized controlled trial was conducted. In phase I, 202 patients with acute upper respiratory tract infection were randomly divided into two groups: trial group (n=101) and control group (n=101). In phase II, 276 patients with acute upper respiratory tract infection were randomly divided into two groups: trial group (n=138) and control group (n=138). The patients in the trial group received andrographolide drop-pill, at a dose of 1.5 g, three times a day; the patients in the control group received andrographolide tablet, at a dose of 1.5 g, three times a day. The therapeutic courses in both groups were 3 days. Clinical symptoms, physical signs, adverse effects, blood, urine and stool tests, hepatorenal function and electrocardiogram were examined before and after the treatment. RESULTS: After treatment in the phase I, the cure rates in the trial group and the control group were 44.55%, 42.57% (full analysis set, FAS) and 45.00%, 43.00% (per protocol set, PPS), and the total obvious rates were 94.06%, 94.06% (FAS) and 95.00%, 95.00% (PPS), respectively. There were no significant differences between the two groups (P>0.05). In the phase II, the cure rates in the trial group and the control group were 39.13%, 33.82% (FAS) and 38.69%, 33.58% (PPS), and the total obvious rates were 96.38%, 96.32% (FAS) and 96.36%, 96.27% (PPS), respectively. There were no significant differences between the two groups (P>0.05) too. No adverse effects were found in the trial. CONCLUSION: Andrographolide drop-pill is effective and safe in the treatment of acute upper respiratory tract infection with external wind-heat syndrome.