Design of a cryptococcus neoformans vaccine by subtractive proteomics combined with immunoinformatics.

The emergence of Cryptococcus neoformans has posed an undeniable burden to many regions worldwide, with its strains mainly entering the lungs through the respiratory tract and spreading throughout the body. Limitations of drug regimens, such as high costs and limited options, have directed our attention toward the promising field of vaccine development. In this study, the subtractive proteomics approach was employed to select target proteins from databases that can accurately cover serotypes A and D of the Cryptococcus neoformans. Further, two multi-epitope vaccines consisting of T and B cell epitopes were demonstrated that they have good structural stability and could bind with immune receptor to induce desired immune responses in silico. After further evaluation, these vaccines show the potential for large-scale production and applicability to the majority of the population of the world. In summary, these two vaccines have been theoretically proven to combat Cryptococcus neoformans infections, awaiting further experimental validation of their actual protective effects.

Long-term cost-effectiveness of transcatheter mitral valve repair in HF patients with secondary mitral regurgitation.

AIMS: The long-term cost-effectiveness of MitraClip in heart failure patients with secondary mitral regurgitation is still unclear. This study aimed to evaluate the long-term cost-effectiveness of MitraClip added to guideline-directed medical therapy vs. guideline-directed medical therapy alone in heart failure patients with secondary mitral regurgitation from the perspective of the healthcare systems of mainland China, the United Kingdom, Germany, and the United States. METHODS AND RESULTS: A two-stage (decision + Markov) model was built. Health utilities were defined by the New York Heart Association class, heart failure re-hospitalization, and death and were calculated based on the 5 year follow-up results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation trial. Direct healthcare costs were derived from the nationally representative data. Future utilities and costs were discounted at country-specific rates. The primary outcome was the lifetime incremental cost-effectiveness ratio. The mean age of the base case in our model was 72.2 years. Over a lifetime horizon, treatment with MitraClip was associated with 829 fewer heart failure re-hospitalizations per 1000 treated patients. The MitraClip treatment was associated with incremental quality-adjusted life-year gains of 0.71, 0.76, 0.78, and 0.78, as well as incremental cost-effectiveness ratios of ¥468 462, £28 910, €26 045, and $71 199 per quality-adjusted life-year for a lifetime horizon in mainland China, the United Kingdom, Germany, and the United States, respectively. In probabilistic sensitivity analysis, 0.2%, 59.4%, 99.6%, and 84.7% of patients were cost-effective in mainland China, the United Kingdom, Germany, and the United States at the country-specific willingness-to-pay thresholds. CONCLUSIONS: MitraClip + guideline-directed medical therapy was cost-effective in heart failure patients with secondary mitral regurgitation in the United Kingdom, Germany, and the United States, but not in mainland China from the perspective of the national healthcare system.

Optimization of doping design for planar P-N homologous junction perovskite solar cells.

In this study, we used the solar cell capacitance simulator (SCAPS) to analyse numerically the performance of perovskite solar cells (PSCs) containing CH3NH3PbI3. The findings indicate that P-N homologous junction processing based on traditional P-I-N PSCs can enhance the photoelectric conversion efficiency (PCE). Furthermore, the authors analyzed the effect of uniform P-N doping of CH3NH3PbI3, concluding that the photoelectric efficiency can be improved from 16.10% to 19.03% after doping. In addition, the optical properties of PSCs under solar irradiation are simulated using finite difference time-domain (FDTD) software under AM1.5. This method is applied to investigate the effect of the P-N uniform junction on the internal electric field generated within the cell. The generation of this electric field promotes carrier separation and transmission, ultimately increasing the open circuit voltage (VOC) of the solar cell from 1.03 to 1.12 V. The usage of P-N junctions enhances PSCs performance and exhibits vast potential for designing and developing PSCs.

Microfluidic Synthesis of Scalable Layer-by-Layer Multiple Antigen Nano-Delivery Platform for SARS-CoV-2 Vaccines.

The COVID-19 outbreak was a global pandemic with wide-ranging healthcare implications. Although several mRNA-based vaccines delivered using lipid nanoparticles (LNP) have been approved and demonstrated efficacy at reducing the severity and spread of infection, continued rapid viral evolution and disadvantages currently associated with LNP delivery vehicles (such as toxicity) are driving the design of next-generation SARS-CoV-2 vaccines. Herein, we describe the development of a trimethylated chitosan-based nanoparticle layer-by-layer (LbL) delivery platform for multiple antigens as a scalable and safe COVID-19 vaccine, known as, "LbL-CoV19". These vaccine candidates have been demonstrated to be biocompatible, safe, and effective at stimulating both humoral and cellular responses for protection in preclinical studies. Preliminary results also indicate that LbL-CoV19 can potentially achieve rapid, long-lasting, and broad protection against the SARS-CoV-2 challenge. The "plug-and-play" platform technology is well suited to preparedness for future pandemics and disease outbreaks.

A Study on the Surface Quality and Damage Properties of Single-Crystal Silicon Using Different Post-Treatment Processes.

Detecting subsurface defects in optical components has always been challenging. This study utilizes laser scattering and photothermal weak absorption techniques to detect surface and subsurface nano-damage precursors of single-crystal silicon components. Based on laser scattering and photothermal weak absorption techniques, we successfully establish the relationship between damage precursors and laser damage resistance. The photothermal absorption level is used as an important parameter to measure the damage resistance threshold of optical elements. Single-crystal silicon elements are processed and post-processed optimally. This research employs dry etching and wet etching techniques to effectively eliminate damage precursors from optical components. Additionally, detection techniques are utilized to comprehensively characterize these components, resulting in the successful identification of optimal damage precursor removal methods for various polishing types of single-crystal silicon components. Consequently, this method efficiently enhances the damage thresholds of optical components.

The Impact of Contrast-Associated Acute Kidney Injury on All-Cause Mortality in Older Patients After Coronary Angiography:A 7.5-year Follow-Up.

Older patients (≥75 years) after coronary angiography constitute an increasing proportion, but only limited data are available regarding the prognosis of geriatric contrast-associated acute kidney injury (CA-AKI). Patients (≥75 years) undergoing coronary angiography between December 2010 and September 2013 were consecutively enrolled. CA-AKI was defined as an increase in serum creatinine of 25% or .5 mg/dL from the baseline within 48-72 h of contrast exposure. All-cause mortality was assessed during median 7.5 years (interquartile range [IQR] 6.7-8.7 years) follow-up period. In total, 571 patients aged >75 years undergoing coronary angiography were enrolled in a single center study; 82 (14.4%) patients had CA-AKI. The all-cause mortality during the median 7.5 years follow-up period was 22.0% in patients with CA-AKI and 13.1% in patients without CA-AKI (P = .015). After adjusting for potential confounding factors, the multivariable analysis indicated that CA-AKI was related to an increased risk of all-cause mortality during the median 7.5-year follow-up (hazard ratio [HR]: 2.46; 95% CI: 1.29-4.7; P = .006). CA-AKI is a significant and independent predictor of long-term mortality for patients aged over 75 years who underwent coronary angiography.

Short Carbon Nanotube-Based Delivery of mRNA for HIV-1 Vaccines.

Developing a safe and effective preventive for HIV-1 remains the hope for controlling the global AIDS epidemic. Recently, mRNA vaccines have emerged as a promising alternative to conventional vaccine approaches, primarily due to their rapid development and potential for low-cost manufacture. Despite the advantages of mRNA vaccines, challenges remain, especially due to the adverse effects of the delivery vehicle and low delivery efficiency. As a result, Luna Labs is developing a short carbon nanotube-based delivery platform (NanoVac) that can co-deliver mRNA and HIV-1 glycoproteins to the immune system efficiently with negligible toxicity. Surface chemistries of NanoVac were optimized to guide antigen/mRNA loading density and presentation. Multiple formulations were engineered for compatibility with both intramuscular and intranasal administration. NanoVac candidates demonstrated immunogenicity in rabbits and generated human-derived humoral and cellular responses in humanized mice (HIS). Briefly, 33% of the HIV-1-infected HIS mice vaccinated with NanoVac-mRNA was cleared of virus infection by 8-weeks post-infection. Finally, NanoVac stabilized the loaded mRNA against degradation under refrigeration for at least three months, reducing the cold chain burden for vaccine deployment.

Identification of Novel Targets for Treatment of Dilated Cardiomyopathy Based on the Ferroptosis and Immune Heterogeneity.

Purpose: This study aimed to investigate the role of ferroptosis in dilated cardiomyopathy (DCM) and to identify new targets for treatment and diagnosis of DCM. Methods: GSE116250 and GSE145154 were downloaded from the Gene Expression Omnibus database. Unsupervised consensus clustering of DCM patients was used to confirm the impact of ferroptosis. Ferroptosis-related hub genes were identified by WGCNA and single cell sequencing analyses. Finally, we established a DCM mouse model via injection of Doxorubicin to verify the expression level of OTUD1 and colocalization between cell markers and OTUD1 in DCM mouse heart. Results: A total of 13 ferroptosis-related differentially expressed genes (DEGs) were identified. The DCM patients were divided into two clusters according to the expression of 13 DEGs. The DCM patients in different clusters showed discrepancies in immune infiltration. Four hub genes were further identified by WGCNA analysis. Single cell data analysis revealed that OTUD1 may regulate B cells and DC cells and then participate in immune infiltration discrepancy. The upregulation of OTUD1 and the colocalization of OTUD1 with CD19 (B cell maker) and CD11c (DCs markers) markers were confirmed in DCM mouse hearts. Conclusion: Ferroptosis and the immune microenvironment are closely associated with DCM, and OTUD1 may play an important role through B cells and DCs.

Simulation Optimization of AlGaN/GaN SBD with Field Plate Structures and Recessed Anode.

This study investigated several AlGaN/GaN Schottky Barrier Diodes (SBDs) with different designs to achieve device optimization. First, the optimal electrode spacing, etching depth, and field plate size of the devices were measured using Technology Computer-Aided Design (TCAD) software by Silvaco, and analysis of the electrical behavior of the device was based on the simulation results, and several AlGaN/GaN SBD chips were designed and prepared. The experimental results revealed that the recessed anode can increase the forward current and reduce the on-resistance. An etched depth of 30 nm could obtain a turn-on voltage of 0.75 V and a forward current density of 216 mA/mm. A breakdown voltage of 1043 V and a power figure of merit (FOM) value of 572.6 MW/cm2 was obtained with a 3 µm field plate. Experiments and simulations confirmed that the recessed anode and field plate structure could increase the breakdown voltage and forward current and improve the FOM value, resulting in higher electrical performance and a wider range of application scenarios.

Does the patellar tendon reflex affect the postural stability in stroke patients with blocked vision?

Background: Stroke patients often show postural instability. The patellar tendon reflex is a basic physical examination for stroke patients. This study aimed to explore the correlation between patellar tendon reflex grade and postural stability among stroke patients. Methods: A total of 37 elderly stroke patients, each with the same quadriceps muscle strength but different patellar tendon reflex levels, were tested on a force platform under eyes-open (EO) and eyes-closed (EC) conditions. Parametric analysis, detrended fluctuation analysis (DFA), and power spectral density (PSD) analysis were used in centre of pressure (COP) signal processing. The correlation between the results of measured data processing and the level of patellar tendon reflex was analysed. Results: All three parameters of COP (the length of the sway trajectory, the mean range of the sway trajectory in the mediolateral [ML] direction [R x ], and the mean range of the sway trajectory in the anterior-posterior [AP] directions [R y ]) were negatively correlated with the patient's patellar tendon reflex grade under the EC condition. The DFA results showed that a higher grade of patellar tendon reflex was associated with a smaller value of the crossover point in the AP direction. Only the PSD values of each frequency band in the AP direction were negatively correlated with patellar tendon reflex grade with EO and became negatively correlated in both AP and ML directions with EC. Overall, the results showed a strong correlation between patellar tendon reflex and postural stability in stroke patients when vision was blocked. Significance: The strong correlation with EC may provide insights into clinic evaluation and treatment for rehabilitation or fall risks of stroke patients.

Prediabetes and all-cause mortality in young patients undergoing coronary artery angiography: a multicenter cohort study in China.

BACKGROUND: The prevalence of prediabetes is increasing in young adults and patients undergoing coronary angiography. However, whether prediabetes is a considerable risk factor for all-cause mortality remains undetermined in young patients undergoing coronary angiography. METHODS: In this study, we retrospectively included 8868 young patients (men aged < 45 years, women aged < 55 years) who underwent coronary angiography (CAG). Patients were categorized as normoglycemic, prediabetes and diabetes according to the HbA1c level or documented history of diabetes. The association of all-cause mortality with diabetes and prediabetes was detected by Cox proportional hazards regression analysis. RESULTS: A total of 3240 (36.5%) among 8868 young patients receiving CAG were prediabetes and 2218 (25.0%) were diabetes. 728 patients died during a median follow-up of 4.92 years. Compared to the normoglycemic group, prediabetes increased the risk of all-cause mortality in young CAG patients by 24%(adjusted HR: 1.24, 95% CI: 1.04-1.49, p = 0.019) and diabetes increased the risk of all-cause mortality by 46%(adjusted HR:1.46, 95% CI:1.2-1.79, p < 0.001). Subgroup analysis showed that diabetes and prediabetes increased the risk of death mainly in patients without comorbidities. CONCLUSION: Prediabetes accounts for more than one-third of the young adults undergoing CAG and was associated with an increased risk of all-cause mortality, active prevention strategy should be considered for these patients.

Mucosal Delivery of HIV-1 Glycoprotein Vaccine Candidate Enabled by Short Carbon Nanotubes.

The HIV-1 envelope glycoprotein spike is the target of antibodies, and therefore represents the main viral antigen for antibody-based vaccine design. One of the challenges in HIV-1 vaccine development is finding efficient ways for the immune system to recognize and respond to HIV-1 without establishing an infection. Since HIV-1 enters the body at mucosal surfaces, induction of immune response at these sites is a preferred preventive approach. Nasal administration is a very effective route for mucosal immunization since it can stimulate mucosal immune responses both locally and distantly. In this paper, Luna develops a safe, short carbon nanotube (CNT)-based, needle-free delivery platform known as "CNTVac". The size of short CNT was controlled to possess HIV-1 particle-like morphology (100-200 nm) capable of efficiently delivering a broad range of antigens intranasally. PEG-Lipid served as the antigen conformation protector and mucosal barrier penetration enhancer (Schematic Figure) was localized between V1V2 antigens, which caused highly enhanced local IgA and systemic antibody IgG responses in mice and rabbits. The short CNT incorporated with PEG-Lipid could not only serve as efficient delivery system but also reduce the amount of lipid usage in order to balance the vaccine dosage in order to eliminate the potential adverse effect. These data suggest a promising platform technology for vaccine delivery.

Layer-by-Layer Delivery of Multiple Antigens Using Trimethyl Chitosan Nanoparticles as a Malaria Vaccine Candidate.

Developing a safe and effective malaria vaccine is critical to reducing the spread and resurgence of this deadly disease, especially in children. In recent years, vaccine technology has seen expanded development of subunit protein, peptide, and nucleic acid vaccines. This is due to their inherent safety, the ability to tailor their immune response, simple storage requirements, easier production, and lower expense compared to using attenuated and inactivated organism-based approaches. However, these new vaccine technologies generally have low efficacy. Subunit vaccines, due to their weak immunogenicity, often necessitate advanced delivery vectors and/or the use of adjuvants. A new area of vaccine development involves design of synthetic micro- and nano-particles and adjuvants that can stimulate immune cells directly through their physical and chemical properties. Further, the unique and complex life cycle of the Plasmodium organism, with multiple stages and varying epitopes/antigens presented by the parasite, is another challenge for malaria vaccine development. Targeting multistage antigens simultaneously is therefore critical for an effective malaria vaccine. Here, we rationally design a layer-by-layer (LbL) antigen delivery platform (we called LbL NP) specifically engineered for malaria vaccines. A biocompatible modified chitosan nanoparticle (trimethyl chitosan, TMC) was synthesized and utilized for LbL loading and release of multiple malaria antigens from pre-erythrocytic and erythrocytic stages. LbL NP served as antigen/protein delivery vehicles and were demonstrated to induce the highest Plasmodium falciparum Circumsporozoite Protein (PfCSP) specific T-cell responses in mice studies as compared to multiple controls. From immunogenicity studies, it was concluded that two doses of intramuscular injection with a longer interval (4 weeks) than traditional malaria vaccine candidate dosing would be the vaccination potential for LbL NP vaccine candidates. Furthermore, in PfCSP/Py parasite challenge studies we demonstrated protective efficacy using LbL NP. These LbL NP provided a significant adjuvant effect since they may induce innate immune response that led to a potent adaptive immunity to mediate non-specific anti-malarial effect. Most importantly, the delivery of CSP full-length protein stimulated long-lasting protective immune responses even after the booster immunization 4 weeks later in mice.

Immunoinformatic screening of Marburgvirus epitopes and computational investigations of epitope-allele complexes.

Marburgvirus (MARV), a member of the Filovirus family, causes severe hemorrhagic fever in humans. Currently, there are no approved vaccines or post exposure treatment methods available against MARV. With the aim of identifying vaccine candidates against MARV, we employ different sequence-based computational methods to predict the MHC-I and MHC-II T-cell epitopes as well as B-cell epitopes for the complete MARV genome. We analyzed the variations in the predicted epitopes among four MARV variants, the Lake Victoria, Angola, Musoke, and Ravn. We used a consensus approach to identify several epitopes, including novel epitopes, and narrowed down the selection based on different parameters such as antigenicity and IC50 values. The selected epitopes can be used in various vaccine constructs that give effective antibody responses. The MHC-I epitope-allele complexes for GP and NP with favorably low IC50 values were investigated using molecular dynamics computations to determine the molecular details of the epitope-allele complexes. This study provides information for further experimental validation of the potential epitopes and the design and development of MARV vaccines.

The U-Shaped Relationship Between Serum Uric Acid and Long-Term All-Cause Mortality in Coronary Artery Disease Patients: A Cohort Study of 33,034 Patients.

Background: Associations between high serum uric acid (SUA) and cardiovascular diseases have been reported. However, few studies have been conducted to explore the relationship between SUA and long-term all-cause mortality in coronary artery disease (CAD) patients. Our study aims to investigate the relationship between SUA and long-term all-cause mortality in patients with CAD. Methods: From January 2007 to December 2018, we divided 33,034 patients with CAD admitted in the Guangdong Provincial People's Hospital into five groups (quintile 1: SUA <5.05 mg/dl, quintile 2: 5.05 mg/dl ≤ SUA <5.59 mg/dl, quintile 3:5.59 mg/dl ≤ SUA <6.8 mg/dl, quintile 4, 6.8 mg/dl ≤ SUA <7.93 mg/dl, and quintile 5, SUA ≥7.93 mg/d;). This study used Kaplan-Meier survival analysis to evaluate patient outcomes with different ranges of SUA. Cox proportional hazards regression models and restricted cubic spline were applied to determine the association between serum uric and long-term all-cause mortality. Results: A total of 33,034 participants were recruited, including 24,780 (75.01%) men and 8,254 (24.99) women in this cohort study. Median follow-up was 4.91 years. We found that SUA is an independent risk factor of long-term all-cause mortality according to the result of Cox proportional hazards models. This study also illustrated an approximate U-shape association between SUA and all-cause mortality when compared with 5.95 mg/lL ≤ SUA <6.8 mg/dl, SUA <5.0 5mg/dl (adjusted hazard ratio (aHR) =1.13, 95% CI: 1.01-1.26, p = 0.03), and SUA ≥8 mg/dL (aHR = 1.18, 95% CI: 1.06-1.32, p = 0.003). Conclusion: Our study indicated a U-shaped relationship between SUA and long-term all-cause mortality in patients with CAD. No matter whether SUA is too high or too low, it increased the all-cause mortality in the CAD population, which deserves to be closely monitored.

Comparison Between Two Definitions of Contrast-Associated Acute Kidney Injury in Patients With Congestive Heart Failure.

Background: Different definitions of contrast-associated acute kidney injury (CA-AKI) have different predictive effects on prognosis. However, few studies explored the relationship between these definitions and long-term prognosis in patients with congestive heart failure (CHF). Thus, we aimed to evaluate this association and compared the population attributable risks (PAR) of different CA-AKI definitions. Methods: This study enrolled 2,207 consecutive patients with CHF undergoing coronary angiography (CAG) in Guangdong Provincial People's Hospital. Two different definitions of CA-AKI were used: CA-AKIA was defined as an increase ≥.5 mg/dl or > 25% in serum creatinine (SCr) from baseline within 72 h after CAG, and CA-AKIB was defined as an increase of ≥.3 mg/dl or > 50% in SCr from baseline within 48 h after CAG. Kaplan-Meier methods and Cox regression were applied to evaluate the association between CA-AKI with long-term mortality. Population attributable risk (PAR) of different definitions for long-term prognosis was also calculated. Results: During the 3.8-year median follow-up (interquartile range 2.1-6), the overall long-term mortality was 24.9%, and the long-term mortality in patients with the definitions of CA-AKIA and CA-AKIB were 30.4% and 34.3%, respectively. We found that CA-AKIA (HR: 1.44, 95% CI 1.19-1.74) and CA-AKIB (HR: 1.48, 95% CI 1.21-1.80) were associated with long-term mortality. The PAR was higher for CA-AKIA (9.6% vs. 8%). Conclusions: Our findings suggested that CA-AKI was associated with long-term mortality in patients with CHF irrespective of its definitions. The CA-AKIA was a much better definition of CA-AKI in patients with CHF due to its higher PAR. For these patients, cardiologists should pay more attention to the presence of CA-AKI, especially CA-AKIA.

First Report of Mango Leaf Blotch Caused by Pseudoplagiostoma mangiferae in Taiwan.

Mango (Mangifera indica L.) is an economically important tropical fruit in southern Taiwan. In February 2019, new leaf blotches distinct from anthracnose lesions were noticed on mango leaves in Meinong, Kaohsiung (N22°54'43.7" E120°32'59.3"). Symptoms were circular to irregular lesions with easily torn centers and were cream to light brown with dark brown margin on both leaf surfaces. Similar symptoms were observed on mango leaves in Yujing, Tainan (N23°07'31.3" E120°27'18.2") in July of the same year. We surveyed the disease incidence on 60 mango trees consisting of three cultivars, 'Irwin', 'Yu-win No.6' and a native cultivar in a commercial farm by randomly examining five shoots of each tree. The disease incidences of 'Irwin', the native cultivar and 'Yu-win No.6' were 25%, 37% and 73%, respectively. Diseased tissues from the two locations were surface sterilized and incubated on potato dextrose agar (PDA) for pathogen isolation. Seven isolates (Mgk3, TMg2-2.2, TMg3-1.2, TMg3-2.1, TMg4-1, TMg6-3, and TMg8-1.1) from different locations and cultivars were selected for further study. Pycnidia were produced on 7-day-old PDA cultures. Conidiogenous cells were hyaline and short cylindrical phialides. Conidia were hyaline, aseptate, thick-walled, 20-24 × 11-16 µm, and subcircular to ellipsoid with 1-2 large oil droplets and a markedly flat protruding hilum at the base. These morphological features presenting in the seven isolates were identified as a member of Pseudoplagiostoma (Cheewangkoon et al. 2010). Pathogenicity assays were conducted by the point inoculation method on 10 intact young leaves growing on 'Irwin' mango plants in a greenhouse at 20-25℃. Each leaf was inoculated at six points on the abaxial surface with point inoculation. Each point was inoculated with a 10 µl conidial suspension (106 conidia/ml) of isolate TMg 8-1.1. Sterilized water was used as control. Shoots with inoculated leaves were covered with translucent plastic bags for 2 days. At 7 days post-inoculation (dpi), 70% of conidia inoculated points (n = 60) displayed symptoms resembling the field symptoms, but sterilized water inoculated points (n = 60) did not. The six other isolates were inoculated on detached leaves by the point inoculation method. All inoculated leaves were maintained in humid containers at 25℃ with 12 h light/dark regime, and displayed similar lesions at 7 dpi. Fungi re-isolated from the symptomatic leaves showed the same morphological characteristics observed in the Pseudoplagiostoma originally isolated from diseased tissues. Internal transcribed spacer (ITS), TUB2 and LSU gene sequences of the seven isolates (ITS accession nos.: MN818659 to MN818665; TUB2 accession nos.: MW415921 to MW415927; LSU accession nos.: MN876849 to MN876855) were amplified with primer sets ITS4/V9G, T1/Bt-2b and LSU1Fd/LR5, respectively, and used for molecular identification (Cheewangkoon et al. 2010). The seven isolate were 95.8%, 99-100% and 99.8% identical to Pseudoplagiostoma mangiferae Dayarathne, Phookamsak & K. D. Hyde KUMCC 18-0179 (the ex-type strain) for the ITS gene (MK084824), TUB2 gene (MK084823) and LSU gene (MK084825), respectively. Phylogenetic analysis based on concatenated sequences of ITS and LSU genes was performed by the Maximum Likelihood method. All seven isolates were clustered in a well-supported clade with P. mangiferae KUMCC 18-0179 with 100% bootstrap value. Based on the pathogenicity and morphological characteristics, the pathogen was identified as P. mangiferae which was reported as a new species associated with mango leaf blight in Yunnan, China (Bezerra et al. 2019; Cheewangkoon et al. 2010; Crous et al. 2012; Crous et al. 2018; Phookamsak et al. 2019; Suwannarach et al. 2016). The newly emerging leaf blotch may become a prevalent disease of mango in future.

Paradoxical Association Between Baseline Apolipoprotein B and Prognosis in Coronary Artery Disease: A 36,460 Chinese Cohort Study.

BACKGROUND: Apolipoprotein B (ApoB) and low-density lipoprotein cholesterol (LDL-C) were identified targets for blood lipid management among coronary artery disease (CAD) patients. However, previous studies reported an inverse correlation between baseline LDL-C concentration and clinical outcomes. This study aims to explore the definite association between baseline ApoB and long-term prognosis. METHODS: A total of 36,460 CAD patients admitted to Guangdong Provincial People's Hospital were enrolled and categorized into two groups: high ApoB (≥65 mg/dL) group and low ApoB (<65 mg/dL) group. The association between baseline ApoB and long-term all-cause mortality was evaluated by the Kaplan-Meier method, Cox regression analyses and restricted cubic splines. RESULTS: The overall mortality was 12.49% (n = 4,554) over a median follow-up period of 5.01 years. Patients with low baseline ApoB levels were paradoxically more likely to get a worse prognosis. There was no obvious difference in risk of long-term all-cause mortality when only adjusted for age, gender, and comorbidity (aHR: 1.07, 95% CI: 0.99-1.16). When CONUT and total bilirubin were adjusted, the risk of long-term all-cause mortality would reduce in the low-ApoB (<65 mg/dL) group (aHR: 0.86, 95% CI: 0.78-0.96). In the fully covariable-adjusted model, patients in the ApoB <65 mg/d group had a 10.00% lower risk of long-term all-cause mortality comparing to patients with ApoB ≥65 mg/dL (aHR: 0.90; 95% CI:0.81-0.99). CONCLUSION: This study found a paradoxical association between baseline ApoB and long-term all-cause mortality. Malnutrition and bilirubin mainly mediate the ApoB paradox. Increased ApoB concentration remained linearly associated with an increased risk of long-term all-cause mortality.

Non-HDL cholesterol paradox and effect of underlying malnutrition in patients with coronary artery disease: A 41,182 cohort study.

BACKGROUND & AIMS: Non-high-density lipoprotein cholesterol (non-HDL-C) and low-density lipoprotein cholesterol (LDL-C) were established as the target for blood lipid management among patients with coronary artery disease (CAD). Previous study reported a negative relation between baseline LDL-C levels and long-term prognosis. However, the association between baseline non-HDL-C concentration and clinical outcomes is unknown. METHODS: A total of 41,182 CAD patients admitted to Guangdong Provincial People's Hospital in China were included in this study from January 2007 to December 2018 and divided into two groups (non-HDL-C < 2.2 mmol/L, n = 3236; non-HDL-C ≥ 2.2 mmol/L, n = 37,946). The Kaplan-Meier method, Cox regression analyses and restricted cubic splines were used to assess the association between non-HDL-C levels and long-term all-cause mortality. RESULTS: The overall mortality was 12.74% (n = 5247) over a median follow-up period of 5.20 years. Kaplan-Meier analysis showed that low non-HDL-C levels were paradoxically associated with a worse prognosis. After adjustment for baseline confounders (e.g., age, sex and comorbidities, etc.), multivariate Cox regression analysis revealed that low non-HDL-C levels (<2.2 mmol/L) were not significantly associated with all-cause mortality (adjusted HR, 1.03; 95% CI, 0.93-1.14). After adjustment for nutritional status, the risk of all-cause mortality in patients with low non-HDL-C levels decreased (adjusted HR, 0.86; 95% CI, 0.78-0.95). In the final multivariate Cox model adjusting for full covariates, low non-HDL-C level was related to better prognosis (adjusted HR, 0.88; 95% CI, 0.80-0.98). CONCLUSION: This study found a paradoxical association between baseline non-HDL-C concentration and long-term all-cause mortality. Malnutrition mainly mediates to the non-HDL-C paradox. Elevated non-HDL-C concentration is still a risk factor of long-term all-cause mortality after considering nutritional status.