Carriage prevalence of Neisseria meningitidis in China, 2005-2022: a systematic review and meta-analysis.

INTRODUCTION: Neisseria meningitidis (Nm) is a major cause of meningitis and septicemia. Most people are infected with latent infections or are carriers. We aimed to estimate the carriage prevalence of Nm in China. METHODS: We did a systematic review of published work to assess the prevalence of meningococcal carriage in China. The quality assessment was conducted by the risk of bias tool according to Damian Hoy's study. We estimated pooled proportions of carriage and its 95% confidence interval (95% CI) using fixed effect model for studies with low heterogeneity and random effect model for studies with moderate or high heterogeneity. Subgroup analyses were also conducted by region and age group. RESULTS: In total, 115 studies were included. The quality evaluation grades of all included documents were medium or high grade. The weighted proportion of carriage was 2.86% (95% CI: 2.25-3.47%, I2: 97.7%, p = 0). The carriage prevalence of Nm varied between provinces, ranged from 0.00% (95% CI: 0.00-0.66%) to 15.50% (95% CI: 14.01-16.99%). Persons aged 15 years and older had the highest carriage 4.38% (95% CI: 3.15-5.62%, I2: 95.4%, p < 0.0001), and children under 6 years of age had the lowest carriage 1.01% (95% CI: 0.59-1.43%, I2: 74.4%, p < 0.0001). In positive carriers, serogroup B (41.62%, 95% CI: 35.25-48.00%, I2: 98.6%, p = 0) took up the highest proportion, and serogroup X (0.02%, 95% CI: 0.00-0.09%, I2: 0.00%, p = 1) accounted for the lowest proportion. CONCLUSION: The meningococcal carriage in China was estimated low and varied by region and age group. Understanding the epidemiology and transmission dynamics of meningococcal infection in insidious spreaders is essential for optimizing the meningococcal immunization strategies of the country.

Over-expression of SlJA2 decreased heat tolerance of transgenic tobacco plants via salicylic acid pathway.

KEY MESSAGE: Over-expression of SlJA2 decreased the accumulation of SA, which resulted in significant physiological and gene expression changes in transgenic tobacco plants, leading to the decreased heat tolerance of transgenic tobacco. NAC family, the largest transcription factors in plants, responses to different environmental stimuli. Here, we isolated a typical NAC transcription factor (SlJA2) from tomato and got transgenic tobacco with SlJA2 over-expression. Expression of SlJA2 was induced by heat stress (42 °C), chilling stress (4 °C), drought stress, osmotic stress, abscisic acid, and salicylic acid. Over-expression of SlJA2 decreased the accumulation of salicylic acid by regulating expression of salicylic acid degradation gene under heat stress. Compared to WT plants, stomatal apertures and water loss increased in transgenic plants, and the damage of photosynthetic apparatus and chlorophyll breakdown were more serious in transgenic plants under heat stress. Meanwhile, more H2O2 and O2·- were accumulated transgenic plants and proline synthesis was restricted, which resulted in more serious oxidative damage compared to WT. qRT-PCR analysis showed that over-expression of SlJA2 could down-regulate genes involved in reactive oxygen species scavenging, proline biosynthesis, and response to heat stress. All the above results indicated that SlJA2 may be a negative regulator responded to plant's heat tolerance. Thus, this study provides new insight into roles of NAC family member in plant response to abiotic stress.

Optical Coherence Tomography Angiography: Revolutionizing Clinical Diagnostics and Treatment in Central Nervous System Disease.

Optical coherence tomography angiography (OCTA), as a new generation of non-invasive and efficient fundus imaging technology, can provide non-invasive assessment of vascular lesions in the retina and choroid. In terms of anatomy and development, the retina is referred to as an extension of the central nervous system (CNS). CNS diseases are closely related to changes in fundus structure and blood vessels, and direct visualization of fundus structure and blood vessels provides an effective "window" for CNS research. This has important practical significance for identifying the characteristic changes of various CNS diseases on OCTA in the future, and plays a key role in promoting early screening, diagnosis, and monitoring of disease progression in CNS diseases. This article reviews relevant fundus studies by comparing and summarizing the unique advantages and existing limitations of OCTA in various CNS disease patients, in order to demonstrate the clinical significance of OCTA in the diagnosis and treatment of CNS diseases.

Tunable rigidity of PLGA shell-lipid core nanoparticles for enhanced pulmonary siRNA delivery in 2D and 3D lung cancer cell models.

Faced with the threat of lung cancer-related deaths worldwide, small interfering RNA (siRNA) can silence tumor related messenger RNA (mRNA) to tackle the issue of drug resistance with enhanced anti-tumor effects. However, how to increase lung tumor targeting and penetration with enhanced gene silencing are the issues to be addressed. Thus, the objective of this study is to explore the feasibility of designing non-viral siRNA vectors for enhanced lung tumor therapy via inhalation. Here, shell-core based polymer-lipid hybrid nanoparticles (HNPs) were prepared via microfluidics by coating PLGA on siRNA-loaded cationic liposomes (Lipoplexes). Transmission electron microscopy and energy dispersive spectroscopy study demonstrated that HNP consists of a PLGA shell and a lipid core. Atomic force microscopy study indicated that the rigidity of HNPs could be well tuned by changing thickness of the PLGA shell. The designed HNPs were muco-inert with increased stability in mucus and BALF, good safety, enhanced mucus penetration and cellular uptake. Crucially, HNP1 with the thinnest PLGA shell exhibited superior transfection efficiency (84.83%) in A549 cells, which was comparable to that of lipoplexes and Lipofectamine 2000, and its tumor permeability was 1.88 times that of lipoplexes in A549-3T3 tumor spheroids. After internalization of the HNPs, not only endosomal escape but also lysosomal exocytosis was observed. The transfection efficiency of HNP1 (39.33%) was 2.26 times that of lipoplexes in A549-3T3 tumor spheroids. Moreover, HNPs exhibited excellent stability during nebulization via soft mist inhaler. In conclusion, our study reveals the great potential of HNP1 in siRNA delivery for lung cancer therapy via inhalation.

Research Progress on the GIP/GLP-1 Receptor Coagonist Tirzepatide, a Rising Star in Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is a chronic progressive metabolic disease that has become a growing health problem worldwide, and the dangers of hyperglycemia and its chronic complications have long been considered a goal of diabetes treatment. In recent years, tirzepatide has become the first dual GIP/GLP-1R agonist approved for the treatment of diabetes mellitus in the United States as a new hypoglycemic medicine. Its hypoglycaemic and weight loss effects have been demonstrated in several large clinical trials, and there is also evidence that it has great potential for cardiovascular protection. In addition, the very concept of synthetic peptides opens up many unknown possibilities for tirzepatide. Ongoing trials (NCT04166773) and evidence suggest that it appears to be a promising drug in the areas of NAFLD, renal, and neuroprotection. Based on preclinical studies and clinical trials, the aim of this article is to discuss the latest clinical developments in tirzepatide, to focus on its differences with other incretin therapies, and to suggest future possibilities and mechanisms of tirzepatide therapy.

Prevalence of Neisseria meningitidis serogroups in invasive meningococcal disease in China, 2010 - 2020: a systematic review and meta-analysis.

Invasive meningococcal disease (IMD) caused by Neisseria meningitidis (Nm) continues to be a global public health concern. Understanding the prevalence of Nm serogroups in IMD is critical for developing strategies for meningococcal vaccination. We used the keywords "cerebrospinal meningitis", "meningococcal", "Neisseria meningitidis'', "meningococcal meningitis", "serogroup'' and "China'' to search five databases, including PubMed, CNKI, CBM (Chinese BioMedical Literature Database), WanFang and VIP from 2010 to 2020. The age distributions, proportions of Nm serogroups and serogroup changes in IMD were analyzed. A total of 14 studies were included according to PRISMA guidelines. In China, from 2010 to 2020, the highest proportion of Nm in IMD was NmC, with 49.7% (95% CI: 35.8%-63.5%), followed by NmB with 30.2% (95%CI:17.3%-43.0%) and NmW with 23.8% (95%CI: 7.0-40.7%). Before 2014, NmC was the major circulating serogroup, with 59.6% (95% CI: 43.8%-75.4%), followed by NmW with 24.4% (95% CI: 5.9%-42.9%). After 2015, IMD cases caused by NmB were increasing, the proportion of NmB reached to 52.4% (95% CI: 31.8%-73.1%). The age groups of children from 0 to 5 years and from 6 to 10 years represented, respectively, 29.6% (95% CI: 16.8%-42.4%) and 28.9% (95% CI: 12.1%-45.8%) of all IMD cases were reported. In China, NmB, NmC and NmW were the major serogroups causing IMD between 2010 and 2020. Since 2015, the proportion of NmB increased rapidly. The current serogroup distribution in China highlights the need of replacing the meningococcal polysaccharide vaccines that are being used in the National Immunization Program with more appropriate vaccines.

Multi-Omics Analysis of Transcriptomic and Metabolomics Profiles Reveal the Molecular Regulatory Network of Marbling in Early Castrated Holstein Steers.

The intramuscular fat (IMF), or so-called marbling, is known as potential determinant of the high quality beef in China, Korea, and Japan. Of the methods that affect IMF content in cattle, castration is markedly regarded as an effective and economical way to improve the deposition of IMF but with little attention to its multi-omics in early-castrated cattle. The aim of this study was to investigate the liver transcriptome and metabolome of early-castrated Holstein cattle and conduct a comprehensive analysis of two omics associated with the IMF deposition using transcriptomics and untargeted metabolomics under different treatments: non−castrated and slaughtered at 16 months of age (GL16), castrated at birth and slaughtered at 16 months of age (YL16), and castrated at birth and slaughtered at 26 months of age (YL26). The untargeted metabolome was analyzed using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The transcriptome of the hepatic genes was analyzed to identify marbling-related genes. Using untargeted metabolomics, the main altered metabolic pathways in the liver of cattle, including those for lipid and amino acid metabolism, were detected in the YL16 group relative to the GL16 and YL26 groups. Significant increases in the presence of betaine, alanine, and glycerol 3-phosphate were observed in the YL16 group (p < 0.05), which might have contributed to the improved beef-marbling production. Compared to the GL16 and YL26 groups, significant increases in the presence of glutathione, acetylcarnitine, and riboflavin but decreases in diethanolamine and 2-hydroxyglutarate were identified in YL16 group (p < 0.05), which might have been beneficial to the beef's enhanced functional quality. The gene expressions of GLI1 and NUF2 were downregulated and that of CYP3A4 was upregulated in the YL16 group; these results were strongly correlated with the alanine, betaine, and leucine, respectively, in the liver of the cattle. In conclusion, implementation of early castration modified the hepatic metabolites and the related biological pathways by regulating the relevant gene expressions, which could represent a better rearing method for production of high marbled and healthier beef products.

Comparisons of adipogenesis- and lipid metabolism-related gene expression levels in muscle, adipose tissue and liver from Wagyu-cross and Holstein steers.

The intramuscular fat (IMF) content and fatty acid composition are important meat quality traits that are mostly affected by the cattle breed. Muscle, adipose tissue and liver are important organs involved in the development of intramuscular adipose tissue. Thus, we hypothesized that there were marked differences in the adipogenesis and lipid metabolism of these tissues between Wagyu-cross and Holstein steers during the finishing phases. To test this hypothesis, we analyzed the expression levels of adipogenesis- and lipid metabolism-related genes in longissimus muscle (LM), subcutaneous fat (SCF) and liver from Wagyu-cross and Holstein steers at 26 months of age. The IMF content and fatty acid profile of LM were determined. Wagyu-cross steers had a higher IMF content and MUFA percentages in the LM than Holstein steers (P<0.05). The relative expression of FGF2, COL1A1, SREBP1c, SCD1, GRP78 and LEP was greater in the LM of Wagyu-cross steers than in Holstein steers (P<0.05). In contrast, Holstein steer SCF had higher (P<0.05) mRNA expression levels of FABP4 and ADIPOQ than Wagyu-cross steers. In the liver, the expression of SREBP1c and GRP78 in Wagyu-cross steers was significantly higher than that in Holstein steers (P<0.05). The results demonstrate that both intramuscular adipogenesis and fibrogenesis are enhanced in Wagyu-cross steers compared with Holstein steers during the finishing phase and that IMF deposition is positively correlated with the maturity of SCF and hepatic lipid accumulation in Wagyu-cross steers.

Femtosecond laser-assisted synthesis of silver nanoparticles and reduced graphene oxide hybrid for optical limiting.

Reduced graphene oxide (rGO) functionalized with silver nanoparticles (Ag NPs) is prepared using a femtosecond laser ablation in liquids method. By ablating the mixed aqueous solutions of silver nitrate and graphene oxide (GO) using femtosecond laser pulses, Ag ions and GO are simultaneously reduced and well-dispersed Ag NPs supported on rGO are obtained. The effect of laser power, irritation time and Ag ion concentration on the optical property and morphology of the products are systematically studied. The nonlinear optical responses of the functionalized graphene are studied using a nanosecond Z-scan technique. The rGO hybrid shows an enhanced nonlinear absorption (NLA) effect compared with GO and rGO, and thus exhibits an excellent optical limiting (OL) property with very low activating threshold, which is estimated to be about 0.38 J cm-2. The enhanced NLA effect in rGO hybrids makes it possible to fabricate solid-state optical limiter, improving the practicality of graphene materials in the OL area.

Heterology expression of the tomato LeLhcb2 gene confers elevated tolerance to chilling stress in transgenic tobacco.

Chilling is one of the most serious environmental stresses that disrupt the metabolic balance of cells and enhance the production of reactive oxygen species (ROS). Light harvesting complex (LHC) proteins had a function in dissipating excess excitation energy and eliminating ROS to maintain the normal physiological function of cells. A tomato (Lycopersicon esculentum) LHC antenna protein gene (LeLhcb2) was isolated. The LeLhcb2-green fluorescent protein (GFP) fusion protein was targeted to the chloroplast of Arabidopsis mesophyll protoplast. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that the expression of LeLhcb2 was markedly abundant in leaves and was induced by chilling (4 °C). qRT-PCR analysis and western blot confirmed that the sense gene LeLhcb2 was transferred into tobacco genome and overexpressed. Under chilling stress, the transgenic plants showed not only better growth, higher fresh weight, chlorophyll content, but also lower malondialdehyde (MDA) accumulation and relative electrical conductivity (REC), compared with the wild type (WT). The maximal photochemical efficiency of PSII (Fv/Fm), non-photochemical quenching (NPQ) and D1 protein content were also higher in the transgenic plants. Furthermore, the relatively lower hydrogen peroxide (H2O2) and superoxide radical (O2(-)) levels in the sense plants were not considered to due to the higher activity of ascorbate peroxidase (APX) and superoxide dismutase (SOD). These results suggested that the overexpression of LeLhcb2 had a key function in alleviating photo-oxidation of PSII and enhanced transgenic tobacco tolerance to chilling stress.