Global incidence and death estimates of chronic kidney disease due to hypertension from 1990 to 2019, an ecological analysis of the global burden of diseases 2019 study.

BACKGROUND: The intricate relationship between hypertension and chronic kidney disease (CKD) presents a global challenge for prevention of hypertension-related CKD. This study's objective is to analyze age, gender, regional disparities, and evolving trends in the disease burden of hypertension-related CKD. We aim to estimate changing spatial and temporal trends in incidence and mortality rates, considering the socio-demographic index (SDI), to inform health strategies effectively. METHOD: Age-standardized incidence rates (ASIR) and death rates (ASDR) were collected from the GBD 2019. Trend analysis was conducted by Joinpoint regression of ASRs from 1990 to 2019. Spatial autocorrelation analysis was performed to obtain spatial patterns. The association between SDI and burden of CKD due to hypertension was estimated using a Pearson correlation analysis. RESULTS: The global ASIR and ASDR due to hypertension-related CKD were 19.45 (95% CI, 17.85 to 21.09) and 5.88 (95% CI, 4.95 to 6.82) per 100 K population in 2019, representing increases of 17.89% and 13.29% compared to 1990, respectively. The elderly population and males were found the highest ASIR and ASDR. The high SDI region had the highest ASIRs, while low SDI regions experienced the highest ASDRs. Joinpoint regression found both global ASIR and ASDR showed increasing trends, with the highest increases observed in middle- and high-SDI regions, respectively. The SDI exhibited a positive association with ASIRs but displayed an inverse V-shaped correlation with the average annual percentage change (AAPC) of ASIRs. Spatial autocorrelation analysis revel significant positive spatial autocorrelation for the AAPC of ASDRs and ASIRs, from 1990 to 2019. CONCLUSIONS: Results met the objectives, and demonstrated a rising global burden of hypertension-related CKD. Factors such as aging, gender, and regional variations should be considered when designing control measures and developing healthcare systems to effectively address the burden of this complex condition.

Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.

High-level production of cordycepin by the xylose-utilising Cordyceps militaris strain 147 in an optimised medium.

Cordycepin is an important active metabolite of Cordyceps militaris. Xylose, an attractive feedstock for producing chemicals through microbial fermentation, cannot be effectively utilised by many reported C. militaris strains. Herein, a xylose-utilising C. militaris strain 147 produced the highest level of cordycepin (3.03 g/L) in xylose culture. Xylose, alanine, and ammonium citrate were determined as the main affecting factors on the cordycepin production using a Plackett-Burman design. The combination of these factors was optimised using response surface methodology, and the maximal 6.54 g/L of cordycepin was produced by the fungus in the optimal medium. Transcriptome analysis revealed that xylose utilisation upregulated the transcriptional levels of genes participating in purine and energy metabolisms in the fungus, which may facilitate the formation of precursors for cordycepin biosynthesis. This investigation provides new insights into the efficient production of cordycepin and is conducive to the valorisation of biomass rich in xylose.

Four New Species of Russula Subsection Sardoninae from China.

Four new species of Russula subsection Sardoninae from northern and southwestern China under coniferous and deciduous trees are proposed as R. begonia, R. photinia, R. rhodochroa, and R. rufa. Illustrations and descriptions of R. gracillima, R. leucomarginata, R. roseola, and the above four new species are provided based on evidence of morphological characters and phylogenetic analyses of the internal transcribed spacer (ITS), as well as the multi-locus of mtSSU, nLSU, rpb1, rpb2 and tef1-α. The relationships between these new species and allied taxa are discussed.

Denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women: A randomized, double-blind, placebo-controlled, multicenter phase III study.

Objectives: This study assessed the efficacy, safety, pharmacokinetics (PK), and immunogenicity profiles of a denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women with a high risk of fracture. Methods: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, 448 postmenopausal women aged 50-85 years with osteoporosis were enrolled at 49 centers in China and were randomly assigned (3:1) to receive 60 â€‹mg of the denosumab biosimilar (LY06006) or placebo subcutaneously every 6 months for 1 year. Lumbar spine bone mineral density (BMD) change was the primary endpoint. Results: Of the 448 randomized patients, 409 (LY06006, n â€‹= â€‹311; placebo, n â€‹= â€‹98) completed the study. All 448 (100.0%) subjects were included in the intent-to-treat (ITT) trial, 427 (95.3%) were included in the full analysis set (FAS), 408 (91.1%) were included in the per protocol set (PPS), 446 (99.6%) were included in the safety set (SS), and 336 (75.0%) were included in the pharmacokinetics concentration set (PKCs). For the primary endpoint, a 4.71% (95% CI, 3.81%, 5.60%) treatment difference in percent change in lumbar spine BMD from baseline to month 12 was observed in the LY06006 group compared with the placebo group (P â€‹< â€‹0.0001). For the secondary endpoints, LY06006 was associated with increased lumbar spine BMD levels measured at month 6, BMD levels at the femoral neck, total hip, and trochanter measured at months 6 and 12 and reduced serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 â€‹N-peptide (P1NP) levels at months 1, 6, and 12. Safety analysis was based on the safety analysis set (SS), and 264 (78.6%) subjects in the LY06006 group and 83 (75.5%) in the placebo group experienced adverse events (AEs). Most events were mild or moderate and not related to the study drugs. Conclusion: In postmenopausal women with a high risk of fracture, LY06006 increased the BMD and decreased bone resorption; thus, LY06006 might be an effective treatment for osteoporosis. LY06006 was generally safe and well tolerated without unexpected adverse reactions, similar to the reference drug Prolia®. The characteristics of effectiveness and safety were similar to those reported in previous studies. The translational potential of this article: In this multi-center, randomized, double-blind, placebo-controlled phase 3 study, LY06006 showed substantially efficacy to increase BMD and well tolerance without unexpected adverse reactions, which is comparable to the reference drug Prolia ®. The presented results are encouraging and can offer some valuable evidence for the clinical practice.

Morpho-Molecular Evidence Reveals Four Novel Species of Gymnopus (Agaricales, Omphalotaceae) from China.

Nine collections of gymnopoid fungi were studied based on morpho-molecular characteristics. The macromorphology was made according to the photograph of fresh basidiomata and field notes, while the micromorphology was examined via an optical microscope. Simultaneously, the phylogenetic analyses were performed by maximum likelihood and Bayesian inference methods based on a combined dataset of nrITS1-nr5.8S-nrITS2-nrLSU sequences. Integrated analysis of these results was therefore, G. efibulatus belonging to sect. Androsacei, G. iodes and G. sinopolyphyllus belonging to sect. Impudicae and G. strigosipes belonging to sect. Levipedes are proposed as new to science. The detailed descriptions, colour photos of basidiomata and line-drawings of microscopic structures are provided. The comparisons with closely related species and a key to known species of Gymnopus s. str. reported with morpho-molecular evidence in China is also given.

Emending Gymnopus sect. Gymnopus (Agaricales, Omphalotaceae) by including two new species from southern China.

Based on phylogenetic analyses, some newly studied Chinese mushroom specimens were found to represent two distinct species within the genus Gymnopus. Along with G.fusipes (sect. Gymnopus) they form a distinct clade with high support, although their macromorphological characters seem to be closer to members of Gymnopus sect. Levipedes or sect. Vestipedes (Collybiopsis). When examined in detail, their micromorphological characters, especially the type of pileipellis, support them as new members of G. sect. Gymnopus. Therefore, two new species, G.omphalinoides and G.schizophyllus, and the emended circumscription of sect. Gymnopus are proposed in this paper. Detailed morphological descriptions, colour photos, illustrations of the two new species, morphological comparisons with similar taxa and the molecular-phylogenetic analyses of the combined nrITS and nrLSU data are presented. A key to the known species of G. sect. Gymnopus is also presented.

Genomic Sequence and Transcriptome Analysis of the Medicinal Fungus Keithomyces neogunnii.

The filamentous fungus Keithomyces neogunnii can infect the larvae of Lepidoptera (Hepialus sp.) and form an insect-fungi complex, which is utilized as an important traditional Chinese medicine. As a valuable medicinal fungus, K. neogunnii produces diverse bioactive substances (e.g., polysaccharide, vitamins, cordycepic acid, and adenosine) under cultivation conditions. Herein, we report the first high-quality genome of the K. neogunnii single-spore isolate Cg7.2a using single-molecule real-time sequencing technology in combination with Illumina sequencing. The assembled genome was 32.6 Mb in size, containing 8,641 predicted genes and having a GC content of 52.16%. RNA sequencing analysis revealed the maximum number of differentially expressed genes in the fungus during the stroma formation stage compared with those during the mycelium stage. These data are valuable to enhance our understanding of the biology, development, evolution, and physiological metabolism of K. neogunnii.

Morphological Characteristics and Molecular Evidence Reveal four New Species of Russula subg. Brevipedum from China.

In this study, four new species of Russula subg. Brevipedum collected from China are described based on morphological characteristics and molecular evidence. Russula brevispora has a white body whose whole parts often stain brownish-orange or grayish-orange, extremely crowded lamellae with the presence of lamellulae, basidiospores with low warts and an inamyloid suprahilar spot, and clavate or lageniform hymenial cystidia often with a papillary or submoniliform appendage. Russula flavescens is characterized by a white pileus often turning yellowish brown when touched, white lamellae turning brown or light orange, basidiospores with an inamyloid suprahilar spot, and fusiform hymenial cystidia often with an appendage. Russula longicollis is morphologically characterized by a white pileus, turning grayish orange when bruised, white lamellae turning pale yellow when bruised, basidiospores with isolated warts and an amyloid suprahilar spot, and fusiform hymenial cystidia usually with a long appendage. Russula pseudojaponica has a yellowish-brown pileus center, yellowish lamellae unchanging when bruised, basidiospores with low warts and an inamyloid suprahilar spot, clavate hymenial cystidia often with a papillary appendage, and clavate pileocystidia with granulose contents. Phylogenetic analyses showed that R. flavescens, R. brevispora, and R. pseudojaponica are members of the subsect. Pallidosporinae, whereas R. longicollis belongs to subsect. Lactarioideae, and is somewhat related to R. leucocarpa.

Three new Russula species in sect. Ingratae (Russulales, Basidiomycota) from southern China.

Three new species of Russulasection Ingratae, found in Guizhou and Jiangsu Provinces, southern China, are proposed: R.straminella, R.subpectinatoides and R.succinea. Photographs, line drawings and detailed morphological descriptions for these species are provided with comparisons against closely-related taxa. Phylogenetic analysis of the internal transcribed spacer (ITS) region supported the recognition of these specimens as new species. Additionally, R.indocatillus is reported for the first time from China and morphological and phylogenetic data are provided for the Chinese specimens.

miR-378a-5p regulates CAMKK2/AMPK pathway to contribute to cerebral ischemia/reperfusion injury-induced neuronal apoptosis.

INTRODUCTION: The pathological mechanism of cerebral ischemia/reperfusion (CIR) injury is complicated and unclear. Apart from the involvement of many low-molecular factors it was found that several miRNAs were dysregulated during and after CIR injury in cell models. This study aimed to explore the effects of miR-378a-5p on in vitro model of (CIR) injury-induced neuronal apoptosis and provide a new mechanism of CIR injury. MATERIAL AND METHODS: Primary hippocampal neurons were isolated from newborn Sprague-Dawley rats. Oxygen- glucose deprivation/reoxygenation (OGDR) for 24 h and 48 h was used as an in vitro model of CIR. Cell viability was measured using MTT assay and apoptosis was determined by flow cytometry. Quantitative real time PCR (qRT-PCR) assay and Western blotting were used to examine mRNA and protein expressions, respectively. TargetScan was used to predict the direct target of miR-378a-5p and luciferase assay was used to validate that calmodulin-dependent protein kinase kinase-2 (CAMKK2) was the direct target of miR-378a-5p. RESULTS: miR-378a-5p expression was significantly increased after OGDR at 24 h and 48 h. After OGDR, cell viability was reduced, which was reversed by miR-378a-5p and enhanced by shCAMKK2 plasmid. Cell apoptosis was increased after OGDR, which was prevented by miR-378a-5p and enhanced by shCAMKK2 plasmid. Results of TargetScan and luciferase assay demonstrated that miR-378a-5p could directly bind to 3'-untranslated region (3'-UTR) of CAMKK2. Both mRNA and protein expression of CAMKK2 were downregulated by miR-378a-5p mimics and upregulated by miR-378a-5p inhibitors. Phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) was positively associated with expression of CAMKK2. CONCLUSIONS: Data of this study indicated that miR-378a-5p was significantly overexpressed after OGDR. miR-378a-5p could bind to 3'-UTR of CAMKK2 to inhibit cell proliferation through regulation of CAMKK2/AMPK pathway providing a new mechanism and biomarker for the diagnosis and potential treatment of CIR injury.

Ophiocordycepsaphrophoridarum sp. nov., a new entomopathogenic species from Guizhou, China.

BACKGROUND: Ophiocordyceps is the largest genus in the family Ophiocordicipitaceae, including many entomopathogenic species. In recent years, many species have been described in this genus, with a wide range of host insects. Entomopathogenic fungi include ecologically, economically and medicinally important species, but a large portion of their diversity remains to be discovered and described. NEW INFORMATION: In this study, a new species, Ophiocordycepsaphrophoridarum sp. nov, parasitising Aphrophoridae sp. (Hemiptera) is proposed from China, based on evidence from morphology and molecular phylogenetic analyses. This species is characterised by fibrous, pigmented stromata, cylindrical asci and filiform ascospores. Compared to its closest relative, O.tricentri, the new species has wider perithecia and longer asci. Molecular phylogenetic analyses of a multilocus dataset (consisting of SSU, ITS, LSU, TEF1, RPB1 and RPB2) confirm its placement in Ophiocordyceps. Ophiocordycepsaphrophoridarum is morphologically described and illustrated with colour photographs. Morphological comparisons with closely-related species are also presented in tabulated format.

[Primary culture of adipose-derived stromal cells].

This study was aimed to explore the methodology regarding culture, proliferation and purification of adipose-derived stromal cells (ADSCs), and to study their biological characteristics. ADSCs were obtained using type I collagenase digestion method. Cell growth was observed, and cell viability were detected under different digestion period by MTT. The ADSCs were then identified and induced. The results showed that adherent cells digested by type I collagenase for 60 min had a strong proliferation capability. After the induction of different inducers these adherent cells could differentiate into nerve cells and fat cells. The best digestion period was proved to be of 60 minutes in the experiment. The results indicate that stem cells with multilineage differentiation ability could be separated from adipose tissue, namely ADSCs.

Wnt3a expression during the differentiation of adipose-derived stem cells into cholinergic neurons.

The present study analyzed changes in Wnt3a expression during differentiation of adipose-derived stem cells into cholinergic neurons. Immunocytochemistry and immunofluorescence revealed significantly increased nestin, neuron-specific enolase, microtubule-associated protein 2, and choline acetyltransferase expression in adipose-derived stem cells isolated from Sprague-Dawley rats and cultured in vitro in neural-induced medium. These expressions increased with prolonged induction time. Real-time reverse transcription-PCR and western blot assay results demonstrated significantly increased choline acetyltransferase and Wnt3a protein and mRNA expressions, respectively, in adipose-derived stem cells following induction. Choline acetyltransferase expression positively correlated with Wnt3a protein and mRNA expressions. These results demonstrated that neural-induced medium induced differentiation of adipose-derived stem cells into cholinergic neuronal-like cells, with subsequent increased Wnt3a expression.

[Association of HLA-A0205 and HLA-A30 with latent autoimmune diabetes in adults].

To investigate the association of HLA-A0205 and HLA-A30 with latent autoimmune diabetes mellius in adults (LADA) in Chengdu Hans, 121 subjects (41 cases of LADA, 40 cases of T2DM, and 40 normal controls) were enrolled in the study. The frequencies of HLA-A0205 and HLA-A30 were determined by nested PCR-SSP and direct sequencing, respectively. The allele frequencies of patient groups and of normal controls were compared by chi-square test using SPSS 11.0 (alpha = 0.05). Hardy-Weinberg equilibrium was tested with use of software HWE (alpha = 0.05). Data from the subjects showed: HLA-A0205 was present in 1 patient with LADA and in 1 normal control (2.44% and 2.5%, respectively), HLA-A30 was present in 2 patients with LADA, in 2 patients with T2DM and in 1 normal control (4.87%, 5.0% and 2.5%, respectively). There was no statistically significant difference between the allele frequencies of the three groups. These results suggest that HLA-A0205, HLA-A30 may not be related to LADA in Chengdu Hans. Yet, further studies with larger sample size may be needed to warrant this conclusion.