Chemodiversity, pharmacological activity, and biosynthesis of specialized metabolites from medicinal model fungi Ganoderma lucidum.

Ganoderma lucidum is a precious fungus, particularly valued for its dual use as both medicine and food. Ganoderic acids (GAs), the distinctive triterpenoids found in the Ganoderma genus, exhibit a wide range of pharmacological activities. However, the limited resources of GAs restrict their clinic usage and drug discovery. In this review, we presented a comprehensive summary focusing on the diverse structures and pharmacological activity of GAs in G. lucidum. Additionally, we discussed the latest advancements in the elucidation of GA biosynthesis, as well as the progress in heterosynthesis and liquid fermentation methods aimed at further increasing GA production. Furthermore, we summarized the omics data, genetic transformation system, and cultivation techniques of G. lucidum, described as medicinal model fungi. The understanding of Ganoderic acids chemodiversity and biosynthesis in medicinal model fungi Ganoderma lucidum will provide important insights into the exploration and utilization of natural products in medicinal fungi.

Manual correction of genome annotation improved alternative splicing identification of Artemisia annua.

Gene annotation is essential for genome-based studies. However, algorithm-based genome annotation is difficult to fully and correctly reveal genomic information, especially for species with complex genomes. Artemisia annua L. is the only commercial resource of artemisinin production though the content of artemisinin is still to be improved. Genome-based genetic modification and breeding are useful strategies to boost artemisinin content and therefore, ensure the supply of artemisinin and reduce costs, but better gene annotation is urgently needed. In this study, we manually corrected the newly released genome annotation of A. annua using second- and third-generation transcriptome data. We found that incorrect gene information may lead to differences in structural, functional, and expression levels compared to the original expectations. We also identified alternative splicing events and found that genome annotation information impacted identifying alternative splicing genes. We further demonstrated that genome annotation information and alternative splicing could affect gene expression estimation and gene function prediction. Finally, we provided a valuable version of A. annua genome annotation and demonstrated the importance of gene annotation in future research.

UiO-66 derived ZrO2@C catalysts for the double-bond isomerization reaction of 2-butene.

1-Butene, as one of the widely used chemical raw materials, can be produced by the double bond isomerization of 2-butene. However, the current yield of the isomerization reaction is only up to 20% or so. It is therefore an urgent issue to develop novel catalysts with higher performances. In this work, a high-activity ZrO2@C catalyst that is derived from UiO-66(Zr) is fabricated. The catalyst is prepared by calcining the precursor UiO-66(Zr) at high temperature in nitrogen, and characterized by XRD, TG, BET, SEM/TEM, XPS and NH3-TPD. The results demonstrate that the calcination temperature has significant influences on the catalyst structure and performance. Regarding the catalyst ZrO2@C-500, the selectivity and yield of 1-butene are 94.0% and 35.1%, respectively. The high performance is due to multiple aspects, including the inherited octahedral morphology from parent UiO-66(Zr), suitable medium-strong acidic active sites and high surface area. The present work will lead to a better understanding of the ZrO2@C catalyst and guide the rational design of high-activity catalysts for the double bond isomerization of 2-butene to 1-butene.

Long-term clinical outcomes of Chinese diabetic patients after coronary revascularization with drug-eluting stents: a retrospective comparative cohort study.

Background: Compared to bare-metal stent implantation, coronary drug-eluting stent (DES) implantation is more likely to reduce restenosis and the need for a subsequent repeat revascularization procedure. Diabetes increases the risk of coronary heart disease and the population of diabetic patients has increased significantly in China in recent years. It's essential to know more about the outcome in these patients underwent DES implantation. To date, the long-term safety and efficacy of coronary DES implantation in Chinese patients with diabetes has rarely been investigated. Methods: In this study, according to inclusion and exclusion criteria, 580 patients who underwent DES implantations between July 2014 and January 2016 were included and divided into the diabetic group (n=173) and non-diabetic group (n=407). Clinical baseline characteristics and follow-up outcomes were collected from electronic medical record. Serial clinical follow-up was conducted at 1-, 3-, and 5-year. The primary end point was a composite of major adverse cardiac events (MACEs), including cardiac death, recurrent myocardial infarction (re-MI), and target lesion revascularization (TLR) in 5-year follow-up. The long-term outcomes observed in the 5-year follow-up period were compared between the diabetic and non-diabetic patients. Results: Non-cardiac death was more common in the diabetic than non-diabetic patients in the 5-year follow-up period (8.7% vs. 3.2% P=0.00). Conversely, the risk of occurrence of MACEs, cardiac death, re-MI, and TLR were comparable. The all-cause mortality rate in 5-year follow-up was higher in the diabetic than non-diabetic patients (14.5% vs. 6.1%, P=0.00). The incidence of stent thrombosis was also comparable between the diabetic and non-diabetic patients. Conclusions: Compared to the non-diabetic patients, the diabetic patients were at higher risk for all-cause mortality after coronary DES implantation during the long-term follow-up period.

The effects of different frequencies of repetitive transcranial magnetic stimulation (rTMS) on patients with swallowing disorders after cerebral infarction.

BACKGROUND: Swallowing disorders represent one of the most common complications after cerebral infarction. OBJECTIVE: To study the effects of different frequencies of repetitive transcranial magnetic stimulation (rTMS) on swallowing disorders after cerebral infarction. METHODS: Ninety patients with swallowing disorder after cerebral infarction were enrolled and randomly assigned to three groups: the 10 Hz frequency rTMS group (30 patients), the 5 Hz frequency rTMS group (30 patients), and the 1 Hz frequency rTMS group (30 patients); another 90 healthy persons without swallowing disorders were included as the control group. The Kubota's water-swallow test, the video fluoroscopic swallow study (VFSS), and the Electroencephalograph (EEG) were analyzed before and after treatment; the EEG of the control group was detected as the baseline. RESULTS: The Kubota's water-swallow test scores were significantly decreased while the scores of pharynx period and the aspiration degree of VFSS significantly increased in 10 Hz frequency rTMS group than before treatment (P≤0.05); the amplitudes of C3 of the EEG significantly increased in three frequency groups than before treatment (P≤0.05). CONCLUSIONS: 10 Hz frequency of rTMS is effective for the treatment of swallowing disorder after cerebral infarction, the excitement of C3 area maybe the therapeutic target of rTMS on swallowing disorder after cerebral infarction.

Lipocalin-2 Regulates Hippocampal Microglial Activation in Poststroke Depression.

Background and Purpose: Microglia play important role in poststroke depression (PSD), however, the exact mechanism was still unclear. The purpose of the study was to study the mechanism of microglial activation in PSD. Methods: 24 rats were randomly divided into three groups: the PSD group (n = 10), the poststroke (PS) group (n = 7), and the sham group (n = 7). Primary hippocampal microglia were isolated and cultured, and recombined LCN2 protein was used to stimulate the cultured microglia. The protein expression of Iba1, P38 MAPK and PP38 MAPK was analyzed by western blotting; the LCN2 expression was measured by RT-qPCR, the serum LCN2 level and the NO level were analyzed by ELISA. Results: Open field test scores (horizontal score, vertical score, and self-grooming score) and the serum LCN2 level were significantly decreased in the PSD group compared with the other two groups (P < 0.05). The serum LCN2 level was positively correlated with the horizontal score and negatively correlated with the self-grooming score in the open field test (P < 0.05). The relative protein level of Iba1 and the LCN2 mRNA level were significantly increased in the hippocampal region compared with other brain regions (P < 0.05), while the relative protein level of Iba1 and the LCN2 mRNA level were significantly increased in the PSD group compared with the other two groups (P < 0.05). The length, supernatant NO level, phagocytic ability and migration ability of LCN2-treated microglia were significantly increased compared with those of untreated microglia (P < 0.05). The relative protein levels of P38 MAPK and the PP38 MAPK significantly increased in hippocampal region in the PSD group and LCN2-treated hippocampal microglia (P < 0.05). Conclusion: Hippocampal microglia are activated during PSD; LCN2 may regulate hippocampal microglial activation by the P38 MAPK pathway in the process of PSD.

Effects of cancer treatment on household impoverishment: a multicentre cross-sectional study in China.

OBJECTIVES: To determine the incidence and intensity of household impoverishment induced by cancer treatment in China. DESIGN: Average income and daily consumption per capita of the households and out-of-pocket payments for cancer care were estimated. Household impoverishment was determined by comparing per capita daily consumption against the Chinese poverty line (CPL, US$1.2) and the World Bank poverty line (WBPL, US$1.9) for 2015. Both pre-treatment and post-treatment consumptions were calculated assuming that the households would divert daily consumption money to pay for cancer treatment. PARTICIPANTS: Cancer patients diagnosed initially from 1 January 2015 to 31 December 2016 who had received cancer treatment subsequently. Those with multiple cancer diagnoses were excluded. DATA SOURCES: A household questionnaire survey was conducted on 2534 cancer patients selected from nine hospitals in seven provinces through two-stage cluster/convenience sampling. FINDINGS: 5.89% (CPL) to 12.94% (WBPL) households were impoverished after paying for cancer treatment. The adjusted OR (AOR) of post-treatment impoverishment was higher for older patients (AOR=2.666-4.187 for ≥50 years vs <50 years, p<0.001), those resided in central region (AOR=2.619 vs eastern, p<0.01) and those with lower income (AOR=0.024-0.187 in higher income households vs the lowest 20%, p<0.001). The patients without coverage from social health insurance had higher OR (AOR=1.880, p=0.040) of experiencing post-treatment household impoverishment than those enrolled with the insurance for urban employees. Cancer treatment is associated with an increase of 5.79% (CPL) and 12.45% (WBPL) in incidence of household impoverishment. The median annual consumption gap per capita underneath the poverty line accumulated by the impoverished households reached US$128 (CPL) or US$212 (WBPL). US$31 170 395 (CPL) or US$115 238 459 (WBPL) were needed to avoid household impoverishment induced by cancer treatment in China. CONCLUSIONS: The financial burden of cancer treatment imposes a significant risk of household impoverishment despite wide coverage of social health insurance in China.

The effects of traditional Chinese medicine sensory stimulation combined with transcranial direct current stimulation on deglutition and related complications in stroke patients with dysphagia: a randomized trial.

BACKGROUND: Stroke is a serious manifestation of a variety of cerebrovascular diseases and can cause significant morbidity and mortality. This study explored the effects of traditional Chinese medicine (TCM) sensory stimulation combined with transcranial direct current stimulation (tDCS) on swallowing function and related complications in stroke patients with dysphagia. METHODS: A total of 60 stroke patients with deglutition dysfunction admitted to our hospital from August 2019 to January 2021 were selected as research subjects. The patients were randomized into 3 different treatment groups, namely, the TCM group, the tDCS group, and the TCM combined with tDCS group (the combined group). Water swallowing tests (WSTs) were conducted to compare the swallowing function before and after treatment. Video fluoroscopic swallowing studies (VFSS) were conducted to analyze the scores of the oral phase, pharyngeal phase, and degree of aspiration. Brain activation and brain volume were examined using functional magnetic resonance imaging (fMRI). RESULTS: The WST and VFSS scores in the combined treatment group were significantly higher than that observed in the other two groups (P<0.05). The fMRI demonstrated that the brain activation volume in the combined treatment group was also greater than that in the other two groups (P<0.05). CONCLUSIONS: TCM combined with tDCS significantly improved deglutition and complications in stroke patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-12001972.

Role and characteristics of hippocampal region microglial activation in poststroke depression.

AIMS: To study the role and characteristics of activated microglia in poststroke depression (PSD) . METHODS: Twenty-four male Wistar rats were randomly divided into three groups: the poststroke (PS) group, PSD group, and Sham group. Neurobehavioral testing was performed 24 h postoperation. The body weights of the rats were regularly recorded, and behavioral testing was regularly performed at 1, 2 and 3 weeks postmodeling. Immunofluorescent staining was used to detect the microglial marker OX42. Real-time PCR was used to analyze the relative gene expression of microglial activation markers (TNF-a, IL-10, IL-1, TGF-ß, CD86, iNOS, CD206, IL-1ß, and Arg1) . RESULTS: The relative gene expression of proinflammatory markers (IL-1, TNF-a, iNOS, and IL1ß) and anti-inflammatory markers (CD206 and Arg1) significantly increased in the hippocampal region compared with that in the right cerebral and left cerebral hemispheres in the PSD group. The relative gene expression of proinflammatory markers (TNF-a, IL-1, iNOS, and CD86) in the hippocampal region was significantly increased in the PSD group compared with that in the Sham and PS groups. The anti-inflammatory markers (TGF-ß and CD206) in the hippocampal region were significantly increased in the PSD group compared with that in the Sham group, and the M2 marker Arg1 was significantly increased in the PSD group compared with that in the PS group. Correlation analysis showed that IL-1 was strongly negatively correlated with PSD . CONCLUSIONS: Most microglia in the hippocampal region of PSD had a proinflammatory status and an anti-inflammatory status. IL-1 showed a strong negative correlation with PSD.

Association Between Programed Cell Death-1 and CD4+ T Cell Alterations in Different Phases of Ischemic Stroke Patients.

Objective: We aimed to analyze alterations in T cell subgroups during different post-ischemic stroke (IS) phases to explore the possible mechanisms underlying stroke-induced immune depression (SIID). Methods: Sixty-four IS patients who met the entry criteria were divided into three groups: an acute phase group, a sub-acute phase group and a stable phase group. Fourteen healthy individuals were selected as normal controls. The phenotype distribution of T cells in patient peripheral blood was analyzed, and the immune checkpoint receptors programed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain 3 (Tim-3) were detected in different T cell phenotypes. Results: Compared with the control group, the absolute number of CD4+ T cells and CD4+ T central memory (TCM) cells was significantly increased in the acute phase group but decreased in the sub-acute phase and stable phase groups compared with that in the acute phase group. PD-1 expression in CD4+ T cells in the stable phase group showed a significant increase compared with that in the acute phase group. The expression of PD-1 on CD4+ TCM cells and CD4+ T effector memory (TEM) cells showed significant decreases in the acute phase compared with control cells; however, in the sub-acute phase and the stable phase, PD-1 expression was significantly increased compared with that in the acute phase. Conclusions: T cell dysfunction, especially CD4+ T cell dysfunction, occurred during different IS phases. PD-1 was highly expressed in CD4+ T cells of different phenotypes after the acute phase and was associated with alterations in CD4+ T cells. Particularly, PD-1 was negatively correlated with the absolute number of TCM cells among different CD4+ T cell phenotypes, which may be one of the possible mechanisms of SIID.

Elevation of plasma neutrophil gelatinase-associated lipocalin (NGAL) levels in schizophrenia patients.

BACKGROUND: Psychiatric diseases are usually accompanied by immune dysregulation and activation of the inflammatory response system. However, the characteristics of immunoinflammatory markers in psychiatric diseases are not well defined. METHODS: Seventy-three patients with psychiatric diseases were divided into four groups, including a schizophrenia group, an anxiety disorder group, a unipolar depression group, and a bipolar disorder group, according to the ICD-10 and DSM-IV codes. Neutrophil gelatinase-associated lipocalin (NGAL) and associated classical immunoinflammatory markers including C-reactive protein (CRP), Th1/Th2 cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ), total leukocyte count (TLC), and neutrophilic granulocyte percentage (NEU%) were analysed; patients with physical diseases were excluded to avoid confounders. Fifteen healthy, age- and gender-matched individuals served as controls. RESULTS: Compared with the corresponding values in the control group, the level of CRP in each psychiatric disease group, the levels of IFN-γ and NGAL in the schizophrenia group, and the NEU% in the depression group were significantly elevated (P < 0.05). Compared with the levels in the schizophrenia group, the levels of CRP in the bipolar disorder and depression groups, the level of IFN-γ in the bipolar disorder group, and the levels of NGAL in the anxiety disorder and depression groups were significantly decreased (P < 0.05). Compared with the depression group, the bipolar disorder group showed significant elevation the NGAL level. LIMITATION: The sample size was relatively small. CONCLUSIONS: Immunoinflammatory markers were elevated in patients with psychiatric diseases, especially schizophrenia. We are the first to report that the level of NGAL is significantly increased in schizophrenia patients.

[Intervention on network craving and encephalofluctuogram in patients with internet addiction disorder: a randomized controlled trial].

OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with psychological interference on abstinence symptom such as network craving and anxiety in internet addiction disorder (IAD) and explore its mechanism. METHODS: One hundred and twenty cases of IAD were randomly divided into EA group, psychotherapy group and EA plus psychotherapy group (combined therapy group). In EA group, Baihui (GV 20), Sishencong (EX-HN 1), Hegu (LI 4), Neiguan (PC 6), Taichong (LR 3) and Sanyinjiao (SP 6) were selected in EA, once every 2 days, for 20 sessions totally. In psychotherapy group, the cognition and behavior therapy was applied, once every 4 days, for 10 sessions totally. In combined therapy group, EA combined with psychological interference was administered. The changes in IAD self-scale table, network craving scale, ZUNG self-rating anxiety scale (SAS) and S spectrum of encephalofluctuogram (ET) were observed before and after treatment. RESULTS: After treatment, the results of IAD self-scale table, network craving scale and ZUNG SAS in combined therapy group were reduced significantly as compared with those before treatment (all P < 0.01) and the score of IAD self-scale table was lower significantly as compared with EA group and psychotherapy group (P < 0.01, P < 0.05), and the score of network craving scale was lower than that in psychotherapy group (P < 0.01). S11 spectrum in combined therapy group decreased significantly as compared with that before treatment (P < 0.05) and was lower significantly as compared with psychotherapy group and EA group (both P < 0.05). CONCLUSION: Electroacupuncture combined with psychological interference can reduce network craving and anxiety of IAD patients and its mechanism is probably related with the decrease of dopamine content in central system.