The Changing and Predicted Trends in Chronic Obstructive Pulmonary Disease Burden in China, the United States, and India from 1990 to 2030.

Background: This study analyzed the burden of chronic obstructive pulmonary disease (COPD) in China, the United States, and India from 1990 to 2019 and projected the trends for the next decade. Methods: This study utilized the GBD 2019 to compare the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years (DALYs) rate, and the proportion attributed to different risk factors in China, the United States, and India. Joinpoint models and autoregressive integrated moving average (ARIMA) models were employed to capture the changing trends in disease burden and forecast outcomes. Results: From 1990 to 2019, China's age-standardized COPD incidence and mortality rates decreased by 29% and 70%, respectively. In the same period, India's rates decreased by 8% and 33%, while the United States saw an increase of 9% in COPD incidence and a 22% rise in mortality rates. Smoking and ambient particulate matter pollution are the two most significant risk factors for COPD, while household air pollution from solid fuels and low temperatures are the least impactful factors in the United States and India, respectively. The proportion of risk from household air pollution from solid fuels is higher in India than in China and the United States. Predictions for 2030 suggest that the age-standardized DALY rates, ASIR, and ASMR in the United States and India are expected to remain stable or decrease, while China's age-standardized incidence rate is projected to rise. Conclusion: Over the past three decades, the incidence of COPD has been decreasing in China and India, while showing a slight increase in the United States. Smoking and ambient particulate matter pollution are the primary risk factors for men and women, respectively. The risk of household air pollution from solid fuels in India needs attention.

Tumor necrosis factor α1 decreases mucosal immune and antioxidant response in the midgut of hybrid fish (white crucian carp ♀ × red crucian carp ♂).

Tumor necrosis factor α1 (TNFα) is a pleiotropic cytokine involved in immune regulation and cellular homeostasis, but the crucial role of TNFα in fish gut remained unclear. The current study aimed to evaluate the immunoregulatory function of TNFα1 on gut barrier in a novel hybrid fish (WR), which was produced by crossing white crucian carp (Carassius cuvieri, ♀) with red crucian carp (Carassius auratus red var, ♂). In this study, WR-tnfα1 sequence was identified, and a high-level expression was detected in the intestine. Elevated levels of WR-tnfα1 expressions were detected in immune-related tissues and cultured fish cells on stimulation. The appearance of vacuolization and submucosal rupture was observed in TNFα1-treated midgut of WR, along with elevated levels of goblet cell atrophy, whereas no significant changes were detected in most expressions of tight-junction genes and mucin genes. In contrast, WR receiving gut perfusion with WR-TNFα1 showed a remarkable decrease in antioxidant status in midgut, whereas the expression levels of apoptotic genes and redox responsive genes increased sharply. These results suggested that TNFα1 could exhibit a detrimental effect on antioxidant defense and immune regulation in the midgut of WR.

Study of Zinc Diffusion Based on S, N-Codoped Honeycomb Carbon Cathodes for High-Performance Zinc-Ion Capacitors.

Capacitors with zinc ions, with excellent stabilities, low cost, and high energy density, are expected to be promising energy storage devices. However, the development of zinc-ion capacitors is quietly restricted by low specific capacity and cycling stability. Herein, to overcome these limitations, honeycomb-structured S, N-codoped carbon (SNPC) is constructed by one-pot calcination of waste corn bracts and thiourea. The honeycomb structure of SNPC is demonstrated to provide abundant active sites that can enhance the extron/ion transport, conductivity for high power export, and ion adsorption capacity in energy storage applications, leading to a higher electrochemical performance achieved. The electrolytes of zinc salt have also been studied. It reveals that the SNPC electrode presents the best electrochemical performance in a 2 M ZnSO4 and 0.5 M ZnCl2 electrolyte mixture because in the electrolyte mixture, Cl- can replace the existing bound water in the solvation structure to form an anion-type water-free solvation structure ZnCl42-. The SNPC-800 electrode with a highly improved surface area (∼909.0 m2 g-1) is proved to be more suitable as the electrode than other materials. Aqueous zinc-ion capacitors (ZICs) have been assembled by the honeycomb-structured SNPC-800 as the cathode, which can achieve a relatively wide working voltage range of 0.1-1.8 V. The SNPC-800 ZICs exhibit a superior specific capacity of 179.1 mA h g-1 at 0.1 A g-1. The energy density of SNPC-800 ZICs reaches an impressive value of 89.6 Wh kg-1 at 53.8 W kg-1, and it sustains 28.3 Wh kg-1 at 1997.6 W kg-1. In addition, there is 99.8% capacity retention in the SNPC-800 ZICs over 5000 cycles. The absorption energy in SPNC is much higher than that in undoped CPC, as confirmed by density functional theory, which reveals that introducing of heteroatoms (S, N) has a comparatively active advantage at increasing the Zn-ion storage capacity. This work proposes a practical strategy for the effective recycling of waste biomass materials into honeycomb carbon electrode materials. Moreover, the honeycomb carbon-based ZICs with excellent electrochemical performance and long-term cycling stability possess great potential to be a superior cathode in practical applications.

GhVOZ1-AVP1 module positively regulates salt tolerance in upland cotton (Gossypium hirsutum L.).

Vascular Plant One­zinc Finger (VOZ) transcription factor can respond to a variety of abiotic stresses, however its function in cotton and the molecular mechanisms of response to salt tolerance remained unclear. In this study, we found that GhVOZ1 is highly expressed in stamen and stem of cotton under normal conditions. The expression of GhVOZ1 increased significantly after 3 h of salt treatment in three-leaf staged upland cotton. Overexpressed transgenic lines of GhVOZ1 in Arabidopsis and upland cotton were treated with salt stress and we found that GhVOZ1 could respond positively to salt stress. GhVOZ1 can regulate Arabidopsis Vacuolar Proton Pump Pyrophosphatase (H+-PPase) gene (AVP1) expression through specific binding to GCGTCTAAAGTACGC site on GhAVP1 promoter, which was examined through Dual-luciferase assay and Electrophoretic mobility shift assay (EMSA). AVP1 expression was significantly increased in Arabidopsis with GhVOZ1 overexpression, while GhAVP1 expression was decreased in virus induced gene silenced (VIGS) cotton plants of GhVOZ1. Knockdown of GhAVP1 expression in cotton plants by VIGS showed decreased superoxide dismutase (SOD) and peroxidase (POD) activities, whereas an increased malondialdehyde (MDA) content and ultimately decreased salt tolerance. The GhVOZ1-AVP1 module could maintain sodium ion homeostasis through cell ion transport and positively regulate the salt tolerance in cotton, providing new ideas and insights for the study of salt tolerance.

Cloning, expression and functional characterization of recombinant tumor necrosis factor α1 (TNFα1) from white crucian carp in gut immune regulation.

TNFα is one of important cytokines belonging to TNF superfamily, which can exhibit a pleiotropic effect in immune modulation, homeostasis as well as pathogenesis. However, its immunoregulatory function on mucosal immunity in fish gut are still unclear. In this study, we aimed to investigated the immunoregulatory role of TNFα1 in midgut of white crucian carp (WCC). WCC-TNFα1 sequence and its deduced structure were firstly identified in WCC. Then, tissue-specific analysis revealed that high-level WCC-TNFα1 expression was detected in gill. After Aeromonas hydrophila and lipopolysaccharide (LPS) stimulated, increased trends of WCC-TNFα1 expressions were detected in immune-related tissues and cultured fish cells, respectively. WCC anal-intubated with WCC-TNFα1 fusion protein showed the increased levels of edema and fuzzy appearance in impaired villi, along with atrophy and reduction of goblet cells (GC). Moreover, the expression levels of tight junction (TJ) genes and mucin genes were consistently lower than those of the control (P < 0.05). WCC-TNFα1 treatment could sharply decrease antioxidant status in midgut, while the expression levels of caspase (CASP) genes, unfolded protein response (UPR) genes and redox response genes increased dramatically. Our results suggested that WCC-TNFα1 could exhibit a detrimental effect on antioxidant and mucosal immune regulation in midgut of WCC.

The rs17782313 polymorphism near MC4R gene confers a high risk of obesity and hyperglycemia, while PGC1α rs8192678 polymorphism is weakly correlated with glucometabolic disorder: a systematic review and meta-analysis.

Background: The relationships of the rs17782313 polymorphism near melanocortin 4 receptor gene (MC4R) and the rs8192678 polymorphism in peroxisome proliferator-activated receptor gamma coactivator 1 alpha gene (PGC1α) with metabolic abnormalities have been explored in many populations around the world, but the findings were not all consistent and sometimes even a bit contradictory. Methods: Electronic databases including Medline, Scopus, Embase, Web of Science, CNKI and Google Scholar were checked for studies that met the inclusion criteria. Data were carefully extracted from eligible studies. Standardized mean differences (SMDs) were calculated by using a random-effects model to examine the differences in the indexes of obesity, glucometabolic disorder and dyslipidemia between the genotypes of the rs17782313 and rs8192678 polymorphisms. Cochran's Q-statistic test and Begg's test were employed to identify heterogeneity among studies and publication bias, respectively. Results: Fifty studies (58,716 subjects) and 51 studies (18,660 subjects) were respectively included in the pooled meta-analyses for the rs17782313 and rs8192678 polymorphisms. The C-allele carriers of the rs17782313 polymorphism had a higher average level of body mass index (SMD = 0.21 kg/m2, 95% confidence interval [95% CI] = 0.12 to 0.29 kg/m2, p < 0.001), waist circumference (SMD = 0.14 cm, 95% CI = 0.06 to 0.23 cm, p < 0.001) and blood glucose (SMD = 0.09 mg/dL, 95% CI = 0.02 to 0.16 mg/dL, p = 0.01) than the TT homozygotes. Regarding the rs8192678 polymorphism, no significant associations with the indexes of obesity, glucometabolic disorder and dyslipidemia were detected. However, significant correlations between the rs8192678 polymorphism and multiple glucometabolic indexes were observed in subgroup analyses stratified by sex, age, ethnicity and health status. Conclusion: The meta-analysis demonstrates that the C allele of the MC4R rs17782313 polymorphism confers a higher risk of obesity and hyperglycemia, and the PGC1α rs8192678 polymorphism is weakly correlated with glucometabolic disorder. These findings may partly explain the relationships between these variants and diabetes as well as cardiovascular disease. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022373543.

Expression and molecular regulation of non-coding RNAs in HPV-positive head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide. Accumulating evidence suggests that persistent HPV infection is closely related to a subset of HNSCC types, and the incidence of human papillomavirus (HPV)-positive HNSCC has been annually increasing in recent decades. Although the carcinogenesis of HPV-positive HNSCC has not been completely elucidated, it has been well confirmed that E6 and E7, the main viral oncoproteins are responsible for the maintenance of malignant transformation, promotion of cell proliferation, and increase in tumor invasion. Moreover, compared with HPV-negative HNSCC, HPV-positive HNSCC shows some special clinical-pathological features, which are possibly related to HPV infection and their specific regulatory mechanisms. Non-coding RNA (ncRNA) is a class of RNA lacking the protein-coding function and playing a critical regulatory role via multiple complex molecular mechanisms. NcRNA is an important regulatory pattern of epigenetic modification, which can exert significant effects on HPV-induced tumorigenesis and progression by deregulating downstream genes. However, the knowledge of ncRNAs is still limited, hence, a better understanding of ncRNAs could provide some insights for exploring the carcinogenesis mechanism and identifying valuable biomarkers in HPV-positive HNSCC. Therefore, in this review, we mainly focused on the expression profile of ncRNAs (including lncRNA, miRNA, and circRNA) and explored their regulatory role in HPV-positive HNSCC, aiming to clarify the regulatory mechanism of ncRNAs and identify valuable biomarkers for HPV-positive HNSCC.

Evaluating SARS-CoV-2 antibody reactivity to natural exposure and inactivated vaccination with peptide microarrays.

Objective: Vaccination is effective tool for preventing and controlling SARS-CoV-2 infections, and inactivated vaccines are the most widely used type of vaccine. In order to identify antibody-binding peptide epitopes that can distinguish between individuals who have been vaccinated and those who have been infected, this study aimed to compare the immune responses of vaccinated and infected individuals. Methods: SARS-CoV-2 peptide microarrays were used to assess the differences between 44 volunteers inoculated with the inactivated virus vaccine BBIBP-CorV and 61 patients who were infected with SARS-CoV-2. Clustered heatmaps were used to identify differences between the two groups in antibody responses to peptides such as M1, N24, S15, S64, S82, S104, and S115. Receiver operating characteristic curve analysis was used to determine whether a combined diagnosis with S15, S64, and S104 could effectively distinguish infected patients from vaccinated individuals. Results: Our findings showed that the specific antibody responses against S15, S64, and S104 peptides were stronger in vaccinators than in infected persons, while responses to M1, N24, S82, and S115 were weaker in asymptomatic patients than in symptomatic patients. Additionally, two peptides (N24 and S115) were found to correlate with the levels of neutralizing antibodies. Conclusion: Our results suggest that antibody profiles specific to SARS-CoV-2 can be used to distinguish between vaccinated individuals and those who are infected. The combined diagnosis with S15, S64, and S104 was found to be more effective in distinguishing infected patients from those who have been vaccinated than the diagnosis using individual peptides. Moreover, the specific antibody responses against the N24 and S115 peptides were found to be consistent with the changing trend of neutralizing antibodies.

Development of MRI-based radiomics predictive model for classifying endometrial lesions.

An unbiased and accurate diagnosis of benign and malignant endometrial lesions is essential for the gynecologist, as each type might require distinct treatment. Radiomics is a quantitative method that could facilitate deep mining of information and quantification of the heterogeneity in images, thereby aiding clinicians in proper lesion diagnosis. The aim of this study is to develop an appropriate predictive model for the classification of benign and malignant endometrial lesions, and evaluate potential clinical applicability of the model. 139 patients with pathologically-confirmed endometrial lesions from January 2018 to July 2020 in two independent centers (center A and B) were finally analyzed. Center A was used for training set, while center B was used for test set. The lesions were manually drawn on the largest slice based on the lesion area by two radiologists. After feature extraction and feature selection, the possible associations between radiomics features and clinical parameters were assessed by Uni- and multi- variable logistic regression. The receiver operator characteristic (ROC) curve and DeLong validation were employed to evaluate the possible predictive performance of the models. Decision curve analysis (DCA) was used to evaluate the net benefit of the radiomics nomogram. A radiomics prediction model was established from the 15 selected features, and were found to be relatively high discriminative on the basis of the area under the ROC curve (AUC) for both the training and the test cohorts (AUC = 0.90 and 0.85, respectively). The radiomics nomogram also showed good performance of discrimination for both the training and test cohorts (AUC = 0.91 and 0.86, respectively), and the DeLong test shows that AUCs were significantly different between clinical parameters and nomogram. The result of DCA demonstrated the clinical usefulness of this novel nomogram method. The predictive model constructed based on MRI radiomics and clinical parameters indicated a highly diagnostic efficiency, thereby implying its potential clinical usefulness for the precise identification and prediction of endometrial lesions.

Yogliptin monotherapy in type 2 diabetes: A 12-week randomized, double-blind, placebo-controlled phase II study.

BACKGROUND: The new xanthine dipeptidyl peptidase-4 inhibitor yogliptin has exhibited excellent hypoglycemic activity in experimental disease models. The present work aimed to assess the efficacy of yogliptin as a monotherapy in individuals with type 2 diabetes mellitus (T2DM). METHODS: A 12-week, double-blind, placebo-controlled phase II study was performed. T2DM patients (new diagnosis or inadequately controlled) were randomly divided into groups (1:1:1:1) and administered either a placebo or weekly doses of 200, 300, or 400 mg yogliptin, respectively. The primary efficacy end point in this analysis was hemoglobin A1c (HbA1c) change at 12 weeks relative to baseline. Relevant secondary outcomes were also examined, including fasting plasma glucose (FPG), 2 h-postprandial plasma glucose (PPG), body weight, and the rate of individuals who achieved the treatment goal of HbA1c ≤ 7% at 12 weeks from baseline. RESULTS: A total of 81 cases who received either the placebo (20 cases) or 200 (20 cases), 300 (20 cases), or 400 (21 cases) mg yogliptin were examined in the full analysis set. At 12 weeks, changes in HbA1c levels from baseline were 0.17 (-0.22, 0.57) in the placebo group, and -0.75 (-1.15, -0.35), -0.52 (-0.93, -0.11) and -1.02 (-1.41, -0.64) (mean % [95% confidence interval], p < .001 vs. placebo) in the 200, 300, and 400 mg yogliptin groups, respectively. From week four, significant improvements in secondary efficacy outcomes among patients administered the yogliptin monotherapy were observed. FPG showed markedly more pronounced reduction after treatment with yogliptin at 200, 300, and 400 mg in comparison with placebo patients at 4, 8, and 12 weeks. At 12 weeks, goal attainment (HbA1c ≤ 7%) was reached in 0%, 20.00%, 15.80%, and 33.33% of the placebo and three Yogliptin dosage groups, respectively. Adverse events were comparable in all groups. CONCLUSIONS: This study demonstrated that yogliptin controlled glycemia in Chinese T2DM cases, with a great safety profile. The current findings supported that any of the three doses of yogliptin, administered once a week, could be used for phase III clinical studies.

Systematic analysis of CNGCs in cotton and the positive role of GhCNGC32 and GhCNGC35 in salt tolerance.

BACKGROUND: Cyclic nucleotide-gated ion channels (CNGCs) are calcium-permeable channels that participate in a variety of biological functions, such as signaling pathways, plant development, and environmental stress and stimulus responses. Nevertheless, there have been few studies on CNGC gene family in cotton. RESULTS: In this study, a total of 114 CNGC genes were identified from the genomes of 4 cotton species. These genes clustered into 5 main groups: I, II, III, IVa, and IVb. Gene structure and protein motif analysis showed that CNGCs on the same branch were highly conserved. In addition, collinearity analysis showed that the CNGC gene family had expanded mainly by whole-genome duplication (WGD). Promoter analysis of the GhCNGCs showed that there were a large number of cis-acting elements related to abscisic acid (ABA). Combination of transcriptome data and the results of quantitative RT-PCR (qRT-PCR) analysis revealed that some GhCNGC genes were induced in response to salt and drought stress and to exogenous ABA. Virus-induced gene silencing (VIGS) experiments showed that the silencing of the GhCNGC32 and GhCNGC35 genes decreased the salt tolerance of cotton plants (TRV:00). Specifically, physiological indexes showed that the malondialdehyde (MDA) content in gene-silenced plants (TRV:GhCNGC32 and TRV:GhCNGC35) increased significantly under salt stress but that the peroxidase (POD) activity decreased. After salt stress, the expression level of ABA-related genes increased significantly, indicating that salt stress can trigger the ABA signal regulatory mechanism. CONCLUSIONS: we comprehensively analyzed CNGC genes in four cotton species, and found that GhCNGC32 and GhCNGC35 genes play an important role in cotton salt tolerance. These results laid a foundation for the subsequent study of the involvement of cotton CNGC genes in salt tolerance.

Cuffless Blood Pressure Monitoring: Academic Insights and Perspectives Analysis.

In recent decades, cuffless blood pressure monitoring technology has been a point of research in the field of health monitoring and public media. Based on the web of science database, this paper evaluated the publications in the field from 1990 to 2020 using bibliometric analysis, described the developments in recent years, and presented future research prospects in the field. Through the comparative analysis of keywords, citations, H-index, journals, research institutions, national authors and reviews, this paper identified research hotspots and future research trends in the field of cuffless blood pressure monitoring. From the results of the bibliometric analysis, innovative methods such as machine learning technologies related to pulse transmit time and pulse wave analysis have been widely applied in blood pressure monitoring. The 2091 articles related to cuffless blood pressure monitoring technology were published in 1131 journals. In the future, improving the accuracy of monitoring to meet the international medical blood pressure standards, and achieving portability and miniaturization will remain the development goals of cuffless blood pressure measurement technology. The application of flexible electronics and machine learning strategy in the field will be two major development directions to guide the practical applications of cuffless blood pressure monitoring technology.

[Metabolic engineering of Escherichia coli for production of malonic acid].

Malonic acid is an important dicarboxylic acid, which can be widely used in the fields of chemical industry, medicine and food. In this study, a recombinant Escherichia coli strain BL21(TPP) was constructed to synthesize malonate through overexpressing six genes of ppc, aspC, panD, pa0132, yneI and pyc. Under shake flask fermentation conditons, strain BL21(TPP) produced 0.61 g/L malonic acid. In a 5 L fermentor, the production of malonic acid reached 3.32 g/L by using an intermittent feeding strategy. Next, a recombinant strain BL21(SCR) was constructed by fusional expression of ppc and aspC, as well as pa0132 and yneI, respectively. As a result, the production of malonic acid increased to 0.83 g/L at the shake flask level, which was a 36% increase over the starting strain BL21(TPP). Finally, the highest malonate production reached 5.61 g/L in a 5 L fermentor, which was a 69% increase over the starting strain BL21(TPP). Production of malonic acid by metabolically engineered E. coli provides a basis for further optimization, and may also serve as a reference for the biosynthesis of other dicarboxylic acids.

Investigation of Antibody Levels During Three Doses of Sinopharm/BBIBP Vaccine Inoculation.

Levels of neutralizing antibodies (NAb) after vaccine against coronavirus disease 2019 (COVID-19) can be detected using a variety of methods. A critical challenge is how to apply simple and accurate methods to assess vaccine effect. In a population inoculated with three doses of the inactivated Sinopharm/BBIBP vaccine, we assessed the performance of chemiluminescent immunoassay (CLIA) in its implementation to detect severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) specific antibodies, as well as the antibody kinetics of healthcare workers throughout the course of vaccination. The antibody levels of NAb, the receptor-binding-domain (RBD) antibodies and IgG peaked one month after the second and remained at a relatively high level for over three months after the booster injection, while IgM and IgA levels remained consistently low throughout the course of vaccination. The production of high-level neutralizing antibodies is more likely when the inoculation interval between the first two doses is within the range of one to two months, and that between the first and booster dose is within 230 days. CLIA showed excellent consistency and correlation between NAb, RBD, and IgG antibodies with the cytopathic effect (CPE) conventional virus neutralization test (VNT). Receiver operating characteristic (ROC) analysis revealed that the optimal cut-off levels of NAb, RBD and IgG were 61.77 AU/ml, 37.86 AU/ml and 4.64 AU/ml, with sensitivity of 0.833, 0.796 and 0.944, and specificity of 0.768, 0.750 and 0.625, respectively, which can be utilized as reliable indicators of COVID-19 vaccination immunity detection.

Transcriptome analysis and co-expression network reveal the mechanism linking mitochondrial function to immune regulation in red crucian carp (Carassius auratus red var) after Aeromonas hydrophila challenge.

Aeromonas hydrophila is a common pathogen of freshwater fish. In this study, A. hydrophila infection was shown to cause tissue damage, trigger physiological changes as well as alter the expression profiles of immune- and metabolic-related genes in immune tissues of red crucian carp (RCC). Transcriptome analysis revealed that acute A. hydrophila infection exerted a profound effect on mitochondrial oxidative phosphorylation linking metabolic regulation to immune response. In addition, we further identified cellular senescence, apoptosis, necrosis and mitogen-activated protein kinase signal pathways as crucial signal pathways in the kidney of RCC subjected to A. hydrophila infection. These findings may have important implications for understanding modulation of immunometabolic response to bacterial infection.

Metabolic engineering of the malonyl-CoA pathway to efficiently produce malonate in Saccharomyces cerevisiae.

Malonate is a platform chemical that has been utilized to synthesize many valuable chemical compounds. Here, Saccharomyces cerevisiae was metabolically engineered to produce malonate through the malonyl-CoA pathway. To construct the key step of converting malonyl-CoA to malonate, a native mitochondrial 3-hydroxyisobutyryl-CoA hydrolase gene EHD3 was mutated to target the cytoplasm and obtain malonyl-CoA hydrolase activity. The malonyl-CoA hydrolase activity of Ehd3 was achieved by mutating the malonyl-CoA binding site F121 to I121 and the active site E124 to seven amino acids (S/T/H/K/R/N/Q). We identified that the strain with E124S mutation had the highest malonate titer with 13.6 mg/L. Genomic integration of the mutant EHD3 and ACC1** to delta sequence sites was further explored to increase their reliable expression. Accordingly, a screening method with the work flow of fluorescence detection, shake-tube fermentation, and shake-flask fermentation was constructed to screen high copy delta sequences efficiently. The malonate titer was improved to 73.55 mg/L after screening the ∼1500 integrative strains, which was increased 4.4-folds than that of the episomal strain. We further engineered the strain by regulating the expression of key enzyme in the malonyl-CoA pathway to improve the precursor supply and inhibiting its competing pathways, and the final engineered strain LMA-16 produced 187.25 mg/L in the flask, 14-fold compared with the initial episomal expression strain. Finally, the combined efforts increased the malonate titer to 1.62 g/L in fed-batch fermentation.

A Comprehensive Identification and Function Analysis of Serine/Arginine-Rich (SR) Proteins in Cotton (Gossypium spp.).

As one of the most important factors in alternative splicing (AS) events, serine/arginine-rich (SR) proteins not only participate in the growth and development of plants but also play pivotal roles in abiotic stresses. However, the research about SR proteins in cotton is still lacking. In this study, we performed an extensive comparative analysis of SR proteins and determined their phylogeny in the plant lineage. A total of 169 SR family members were identified from four Gossypium species, and these genes could be divided into eight distinct subfamilies. The domain, motif distribution and gene structure of cotton SR proteins are conserved within each subfamily. The expansion of SR genes is mainly contributed by WGD and allopolyploidization events in cotton. The selection pressure analysis showed that all the paralogous gene pairs were under purifying selection pressure. Many cis-elements responding to abiotic stress and phytohormones were identified in the upstream sequences of the GhSR genes. Expression profiling suggested that some GhSR genes may involve in the pathways of plant resistance to abiotic stresses. The WGCNA analysis showed that GhSCL-8 co-expressed with many abiotic responding related genes in a salt-responding network. The Y2H assays showed that GhSCL-8 could interact with GhSRs in other subfamilies. The subcellular location analysis showed that GhSCL-8 is expressed in the nucleus. The further VIGS assays showed that the silencing of GhSCL-8 could decrease salt tolerance in cotton. These results expand our knowledge of the evolution of the SR gene family in plants, and they will also contribute to the elucidation of the biological functions of SR genes in the future.

Comparative analysis on the immunoregulatory roles of ferritin M in hybrid fish (Carassius cuvieri ♀ × Carassius auratus red var ♂) and its parental species after bacterial infection.

Ferritin M is involved in the regulation of fish immunity. In this study, open reading frame (ORF) sequences of ferritin M from hybrid fish and its parental species were 534 bp. Tissue-specific analysis indicated that the highest level of ferritin M from red crucian carp was observed in kidney, while peaked expressions of ferritin M from white crucian carp and hybrid carp were observed in gill. Elevated levels of ferritin M from hybrid carp and its parental species were detected in immune-related tissues following Aeromonas hydrophila infection or in cultured fish cell lines after lipopolysaccharide (LPS) challenge. Ferritin M overexpression could attenuate NF-κB and TNFα promoter activity in their respective fish cells. Purified ferritin M fusion proteins elicited in vitro binding activity to A. hydrophila and Edwardsiella tarda, lowered bacterial dissemination to tissues and alleviated inflammatory response. Furthermore, treatment with ferritin M fusion proteins could mitigate bacteria-induced liver damage and rescue antioxidant activity. These results suggested that ferritin M in hybrid fish showed a similar immune defense against bacteria infection in comparison with those of its parental species.

Humoral immune response of BBIBP COVID-19 vaccination before and after the booster immunization.

BACKGROUND: The inactivated Sinopharm/BBIBP COVID-19 vaccine has been widely used in the world and has joined the COVAX vaccine supply program for developing countries. It is also well adapted for usage in low- and middle-income nations due to their low storage requirements. OBJECTIVE: This study aims to report on the kinetics, durability, and neutralizing ability of the induced immunity of the BBIBP vaccine, and the intensified antibody response elicited by the booster. METHODS: A total of 353 healthy adult participants, aged 20-74 years, were recruited in this multicenter study. A standard dose of the BBIBP vaccine was administered (Month 0), followed by a second standard dose (Month 1), and a booster dose (after Month 7). Vaccine-induced virus-specific antibody levels (SARS-CoV-2-IgA/IgM/IgG), conventional virus neutralization test (cVNT), pseudovirus neutralization test (pVNT), and surrogate virus neutralization test (sVNT) were monitored over multiple time points. RESULTS: Neutralizing titers induced by the two doses of inactivated vaccine for COVID-19 peaked at Month 2 and declined to 33.89% at Month 6. Following the booster dose, elevated levels of antibodies were induced for IgA, IgG, and neutralizing antibodies, with neutralizing titer reaching 13.2 times that of before the booster. CONCLUSION: By monitoring the antibody titer levels postvaccination, this study has shown that serum antibody levels will decrease over time, but a notable spike in antibody levels postbooster highlights the anamnestic immune response. This signifies that the protection capability has increased following the injection of booster immunization.

Programmable Synthetic Upstream Activating Sequence Library for Fine-Tuning Gene Expression Levels in Saccharomyces cerevisiae.

A wide dynamic range of promoters is necessary for fine-tuning transcription levels. However, weak intensity and narrow dynamic range limit transcriptional regulation via constitutive promoters. The upstream activation sequence (UAS) located upstream of the core promoter is a crucial region that could obviously enhance promoter strength. Herein, we created a random mutagenesis library consisting of 330 different variants based on the UAS of the TDH3 promoter with an ∼37-fold dynamic range by error-prone polymerase chain reaction (PCR) and obtained strong intensity mutant UAS, which was ∼12-fold greater than the wild-type UASTDH3. Analysis of the mutant library revealed 15 strength-enhancing sites and their corresponding bases of the UASTDH3 regions, which provided the impetus for a synthetic library. The resulting 32 768 mutant UAS library was constructed by permutation and combination of the bases of the 15 enhancing sites. To characterize the library, a strength prediction model was built by correlating DNA structural features and UAS strength, which provided a model between UAS sequence and intensity. Following characterization, the UAS library was applied to precisely regulate gene expression in the production of ß-carotene, proving that the UAS library would be a useful tool for gene tuning in metabolic engineering. In summary, we designed, constructed, and characterized a UAS library that facilitated precise tuning of transcription levels of target proteins.