Efficacy and safety of sacubitril/allisartan for the treatment of primary hypertension: a phase 2 randomized, double-blind study.

This randomized, double-blind phase 2 study assessed the efficacy and safety of sacubitril/allisartan, an angiotensin receptor neprilysin inhibitor, compared with placebo in Chinese patients with mild to moderate hypertension. Eligible patients aged 18-75 years (n = 235) with mild to moderate hypertension were randomized to receive sacubitril/allisartan 120 mg (n = 52), sacubitril/allisartan 240 mg (n = 52), sacubitril/allisartan 480 mg (n = 52), placebo (n = 26) or olmesartan 20 mg (n = 53) once daily for 8 weeks. The primary end point was a reduction in clinic systolic blood pressure from baseline with different doses of sacubitril/allisartan versus placebo at 8 weeks. Secondary efficacy variables included clinic diastolic blood pressure and 24-h ambulatory blood pressure for the comparison between sacubitril/allisartan and placebo at 8 weeks. Safety assessments included all adverse events and serious adverse events. Sacubitril/allisartan 480 mg/day provided a significantly greater reduction in clinic systolic blood pressure than placebo at 8 weeks (between-treatment difference: -9.1 mmHg [95% confidence interval -1.6 to -16.6 mmHg], P = 0.02). There were also significant reductions in 24-h, daytime and nighttime systolic and diastolic blood pressure for sacubitril/allisartan 480 mg/day compared with placebo (P ≤ 0.03). Similarly, a greater reduction in daytime systolic blood pressure was observed for sacubitril/allisartan 240 mg/day compared with placebo (between-treatment difference: -7.3 mmHg [95% confidence interval -0.5 to -14.0 mmHg], P = 0.04). Sacubitril/allisartan was well tolerated, and no cases of angioedema were reported. Sacubitril/allisartan is effective for the treatment of hypertension in Chinese patients and is well tolerated.

Clinical guideline on magnetically controlled capsule gastroscopy (2021 edition).

With the development and generalization of endoscopic technology and screening, clinical application of magnetically controlled capsule gastroscopy (MCCG) has been increasing. In recent years, various types of MCCG are used globally. Therefore, establishing relevant guidelines on MCCG is of great significance. The current guidelines containing 23 statements were established based on clinical evidence and expert opinions, mainly focus on aspects including definition and diagnostic accuracy, application population, technical optimization, inspection process, and quality control of MCCG. The level of evidence and strength of recommendations were evaluated. The guidelines are expected to guide the standardized application and scientific innovation of MCCG for the reference of clinicians.

Bordetella spp. utilize the type 3 secretion system to manipulate the VIP/VPAC2 signaling and promote colonization and persistence of the three classical Bordetella in the lower respiratory tract.

Introduction: Bordetella are respiratory pathogens comprised of three classical Bordetella species: B. pertussis, B. parapertussis, and B. bronchiseptica. With recent surges in Bordetella spp. cases and antibiotics becoming less effective to combat infectious diseases, there is an imperative need for novel antimicrobial therapies. Our goal is to investigate the possible targets of host immunomodulatory mechanisms that can be exploited to promote clearance of Bordetella spp. infections. Vasoactive intestinal peptide (VIP) is a neuropeptide that promotes Th2 anti-inflammatory responses through VPAC1 and VPAC2 receptor binding and activation of downstream signaling cascades. Methods: We used classical growth in vitro assays to evaluate the effects of VIP on Bordetella spp. growth and survival. Using the three classical Bordetella spp. in combination with different mouse strains we were able to evaluate the role of VIP/VPAC2 signaling in the infectious dose 50 and infection dynamics. Finally using the B. bronchiseptica murine model we determine the suitability of VPAC2 antagonists as possible therapy for Bordetella spp. infections. Results: Under the hypothesis that inhibition of VIP/VPAC2 signaling would promote clearance, we found that VPAC2-/- mice, lacking a functional VIP/VPAC2 axis, hinder the ability of the bacteria to colonize the lungs, resulting in decreased bacterial burden by all three classical Bordetella species. Moreover, treatment with VPAC2 antagonists decrease lung pathology, suggesting its potential use to prevent lung damage and dysfunction caused by infection. Our results indicate that the ability of Bordetella spp. to manipulate VIP/VPAC signaling pathway appears to be mediated by the type 3 secretion system (T3SS), suggesting that this might serve as a therapeutical target for other gram-negative bacteria. Conclusion: Taken together, our findings uncover a novel mechanism of bacteria-host crosstalk that could provide a target for the future treatment for whooping cough as well as other infectious diseases caused primarily by persistent mucosal infections.

The Co-Association of Enterobacteriaceae and Pseudomonas with Specific Resistant Cucumber against Fusarium Wilt Disease.

The root microbiota contributes to the plant's defense against stresses and pathogens. However, the co-association pattern of functional bacteria that improves plant resistance has not been interpreted clearly. Using Illumina high-throughput sequencing technology, the root bacterial community profiles of six cucumber cultivars with different resistance in response to the causative agent of cucumber Fusarium wilt (CFW), Fusarium oxysporum f. sp. cucumerinum (Foc), were analyzed. The principal coordinate analysis indicated that the interactions of the cultivars and pathogens drove the cucumber root bacterial communities (p = 0.001). The resistance-specific differential genera across the cultivars were identified, including Massilia in the resistant cultivars, unclassified Enterobacteriaceae in resistant CL11 and JY409, Pseudomonas in JY409, Cronobacter in moderately resistant ZN106, and unclassified Rhizobiaceae and Streptomyces in susceptible ZN6. The predominant root bacterium Massilia accounted for the relative abundance of up to 28.08-61.55%, but dramatically declined to 9.36% in Foc-inoculated susceptible ZN6. Pseudomonas ASV103 and ASV48 of Pseudomonadaceae and Cronobacter ASV162 of Enterobacteriaceae were consistently differential across the cultivars at the phylum, genus, and ASV levels. Using the culture-based method, antagonistic strains of Enterobacteriaceae with a high proportion of 51% were isolated. Furthermore, the bacterial complexes of Pantoea dispersa E318 + Pseudomonas koreensis Ps213 and Cronobacter spp. C1 + C7 reduced the disease index of CFW by 77.2% and 60.0% in the pot experiment, respectively. This study reveals the co-association of specific root bacteria with host plants and reveals insight into the suppressing mechanism of resistant cultivars against CFW disease by regulating the root microbiota.

High expression of prolyl 4-hydroxylase subunit alpha-2 in lung adenocarcinoma indicates poor prognosis.

OBJECTIVE: To analyze the Prolyl 4-Hydroxylase subunit Alpha-2 (P4HA2) expression in Lung Adenocarcinoma (LAUD). METHODS: The authors assessed P4HA2 expression in the LUAD tumor ecosystem using single-cell analysis. The authors analyzed the relationship between P4HA2 expression and clinical features in LUAD and Brain Metastasis (BM) cases. The authors assessed the biological functions of P4HA2 using The Cancer Genome Atlas-LUAD dataset. RESULTS: P4HA2 was more highly expressed in fibroblasts than in epithelial cells in normal lung and lung adenocarcinoma tissues (p < 0.001). P4HA2 was more highly expressed in malignant epithelial cells than in fibroblasts in the BM tissue (p = 0.002). P4HA2 expression was significantly higher in female cases than in male cases (p = 0.049) and was related to lymph node metastasis (p = 0.019) and a higher TNM stage (p = 0.020). High P4HA2 expression indicated a poor prognosis and served as an independent prognostic risk factor in lung cancer. P4HA2 was mainly enriched in the extracellular matrix organization, NADH regeneration, and canonical glycolysis. P4HA2 expression was negatively correlated with naive B cells, T-cells, CD8, and activated natural killer cells, but positively correlated with CD4 memory-activated T cells, regulatory T-cells, resting dendritic cells, and dendritic cell activation. P4HA2 messenger RNA expression was correlated with programmed death-ligand 1 and cytotoxic T-lymphocyte-associated protein 4. CONCLUSION: P4HA2 is highly expressed in LUAD tumor cells, especially for the BM subtype, and is a valuable prognostic indicator of LUAD. It may be involved in a biological activity of distant metastasis of LUAD tumor cells and serve as a potential treatment target.

An effective and chemotherapy-free strategy of all-trans retinoic acid and arsenic trioxide for acute promyelocytic leukemia in all risk groups (APL15 trial).

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has been demonstrated to have comparable effectiveness or better to ATRA and chemotherapy (CHT) in non-high-risk acute promyelocytic leukemia (APL). However, the efficacy of ATRA-ATO compared to ATRA-ATO plus CHT in high-risk APL remains unknown. Here we performed a randomized multi-center non-inferiority phase III study to compare the efficacy of ATRA-ATO and ATRA-ATO plus CHT in newly diagnosed all-risk APL to address this question. Patients were assigned to receive ATRA-ATO for induction, consolidation, and maintenance or ATRA-ATO plus CHT for induction followed by three cycles of consolidation therapy, and maintenance therapy with ATRA-ATO. In the non-CHT group, hydroxyurea was used to control leukocytosis. A total of 128 patients were treated. The complete remission rate was 97% in both groups. The 2-year disease-free, event-free survival rates in the non-CHT group and CHT group in all-risk patients were 98% vs 97%, and 95% vs 92%, respectively (P = 0.62 and P = 0.39, respectively). And they were 94% vs 87%, and 85% vs 78% in the high-risk patients (P = 0.52 and P = 0.44, respectively). This study demonstrated that ATRA-ATO had the same efficacy as the ATRA-ATO plus CHT in the treatment of patients with all-risk APL.

Tracing brain genotoxic stress in Parkinson's disease with a novel single-cell genetic sensor.

To develop an in vivo tool to probe brain genotoxic stress, we designed a viral proxy as a single-cell genetic sensor termed PRISM that harnesses the instability of recombinant adeno-associated virus genome processing and a hypermutable repeat sequence-dependent reporter. PRISM exploits the virus-host interaction to probe persistent neuronal DNA damage and overactive DNA damage response. A Parkinson's disease (PD)-associated environmental toxicant, paraquat (PQ), inflicted neuronal genotoxic stress sensitively detected by PRISM. The most affected cell type in PD, dopaminergic (DA) neurons in substantia nigra, was distinguished by a high level of genotoxic stress following PQ exposure. Human alpha-synuclein proteotoxicity and propagation also triggered genotoxic stress in nigral DA neurons in a transgenic mouse model. Genotoxic stress is a prominent feature in PD patient brains. Our results reveal that PD-associated etiological factors precipitated brain genotoxic stress and detail a useful tool for probing the pathogenic significance in aging and neurodegenerative disorders.

Differences in clinical characteristics and lesion proteomics between inflammatory linear verrucous epidermal nevus and local verrucous epidermal nevus.

BACKGROUND: Verrucous epidermal nevus (VEN) are keratinocytic epidermal nevus that appear at birth or in early childhood. They exhibit a range of manifestations, depending on the patient's age. VEN are rarely encountered in clinical practice, and the systemic and comprehensive clinical characteristics of VEN have not been well investigated. Furthermore, the association between tandem mass tag (TMT)-based quantitative proteomics and the VEN phenotype is still unclear. OBJECTIVES: This study investigated the differences in the clinical characteristics and lesion proteomics between inflammatory linear VEN (ILVEN) and local VEN. METHODS: This retrospective study enrolled 125 patients with histopathologically diagnosed VEN who presented to our hospital between 2019 and 2021. We collected the clinical data of all patients with VEN using a self-designed questionnaire. The expression of proteins in VEN lesions was analyzed using TMT proteomics technology. RESULTS: In total, there were 125 patients with VEN that were evaluated, including 67 (53.60%) patients with local VEN and 58 (46.40%) with ILVEN. No significant differences were found in sex, onset age, and lesion location between patients with local VEN and those with ILVEN (all P > 0.05). Significant differences were found in the onset site and pruritus scores between patients with ILVEN and those with local VEN (all P < 0.05). According to the TMT proteomics results, 89 proteins were up or downregulated with at least 1.3-fold (upregulated: 38, downregulated: 51; P < 0.05) in ILVEN lesions relative to VEN lesions. The top 10 differentially expressed proteins between ILVEN and local VEN lesions were OGN, NT5C3A, ADD1, OLFML1, DHRS1, CALML5, SAMHD1, SFRP2, SPRR1B, and SERPINB13. The upregulated proteins are mainly involved in neutrophil activation, neutrophil-mediated immunity, and p53 signaling pathway (hsa04115). The downregulated proteins are mainly involved in cellular response to cytokine stimulus, cell adhesion, Th1 and Th2 cell differentiation. In total, based on the differentially expressed proteins between ILVEN and local VEN, five pathways that may be associated with the pathogenesis of inflammation, including CAMs (P = 0.006), Th1 and Th2 cell differentiation (P = 0.017), PPAR signaling pathway (P = 0.023), Th17 cell differentiation (P = 0.024), and p53 signaling pathway (P = 0.041). CONCLUSIONS: Clinical data of the patients revealed that ILVEN lesions presented with intense pruritus and inflammatory change. Differentially expressed proteins between ILVEN and local VEN are mainly involved in multiple inflammation related pathways associated with the pathogenesis mechanisms of pruritus. LIMITATIONS: The small sample size in clinical characteristic and proteomics study is one of the most significant limitations in our study. The inflammation associated proteins and signal pathways in the pathogenesis of pruritus in ILVEN is not explored. SIGNIFICANCE: In this study, we found the lesions of ILVEN patients presented with intense pruritus and inflammational change. A total of 89 proteins were up or downregulated with at least 1.3-fold (upregulated: 38, downregulated: 51; P < 0.05) in ILVEN lesions relative to VEN lesions. On the other hand, the etiology of itch in ILVEN mainly associated with inflammation, but the exact mechanisms was still unclear. We found the differentially expressed proteins between ILVEN and local VEN enriched five pathways that may be associated with the pathogenesis of inflammation and pruritus.

Perceived Importance of Breast Cancer Risk Factors: A Survey on 386 Physicians in China.

There are varying definitions of women at high risk of breast cancer across different institutions, and there are reports suggesting that the breast cancer risk assessment tools have not been well integrated into clinical practice. In this study, we tried to investigate the perceived importance of different breast cancer risk factors by physicians in China. A cross-sectional survey involving 386 anonymous physicians was conducted using a 20-item, 5-point Likert scale questionnaire. The Kruskal-Wallis test and post-hoc pairwise comparisons were used to compare the differences in response. Most of the respondents were either breast surgeons/specialists (n=161; 41.7%) or medical oncologists (n=151; 39.1%), and the results showed that the breast cancer risk factors were not perceived as equally important. The weighting of each risk factor also varied depending on the physician's medical specialty, location of practice, and the number of years of clinical experience.  This study provides a more updated insight into the perceptions of physicians in China toward the breast cancer risk factors, as well as underlines the potential improvements in breast cancer risk assessment strategies that can be done.

High expression of prolyl 4-hydroxylase subunit alpha-2 in lung adenocarcinoma indicates poor prognosis

Abstract Objective To analyze the Prolyl 4-Hydroxylase subunit Alpha-2 (P4HA2) expression in Lung Adenocarcinoma (LAUD). Methods The authors assessed P4HA2 expression in the LUAD tumor ecosystem using single-cell analysis. The authors analyzed the relationship between P4HA2 expression and clinical features in LUAD and Brain Metastasis (BM) cases. The authors assessed the biological functions of P4HA2 using The Cancer Genome Atlas-LUAD dataset. Results P4HA2 was more highly expressed in fibroblasts than in epithelial cells in normal lung and lung adenocarcinoma tissues (p < 0.001). P4HA2 was more highly expressed in malignant epithelial cells than in fibroblasts in the BM tissue (p = 0.002). P4HA2 expression was significantly higher in female cases than in male cases (p = 0.049) and was related to lymph node metastasis (p = 0.019) and a higher TNM stage (p = 0.020). High P4HA2 expression indicated a poor prognosis and served as an independent prognostic risk factor in lung cancer. P4HA2 was mainly enriched in the extracellular matrix organization, NADH regeneration, and canonical glycolysis. P4HA2 expression was negatively correlated with naive B cells, T-cells, CD8, and activated natural killer cells, but positively correlated with CD4 memory-activated T cells, regulatory T-cells, resting dendritic cells, and dendritic cell activation. P4HA2 messenger RNA expression was correlated with programmed death-ligand 1 and cytotoxic T-lymphocyte-associated protein 4. Conclusion P4HA2 is highly expressed in LUAD tumor cells, especially for the BM subtype, and is a valuable prognostic indicator of LUAD. It may be involved in a biological activity of distant metastasis of LUAD tumor cells and serve as a potential treatment target.

Ambulatory blood pressure in relation to interaction between dietary sodium intake and serum uric acid in the young.

PURPOSE: We hypothesise that dietary sodium intake interacts with serum uric acid to influence blood pressure (BP) in children and adolescents. In the present study, we investigated ambulatory BP in relation to hyperuricaemia, dietary sodium intake and their interaction in children and adolescents with hypertension. MATERIALS AND METHODS: A total of 616 study participants were 10-24 years old and had primary hypertension diagnosed after admission in a specialised inpatient ward. Ambulatory BP monitoring was performed during hospitalisation. 24-h urine was collected for measurements of electrolytes. Hyperuricaemia was defined as a serum uric acid of ≥327.25 µmol/L in patients <18 years old and of ≥420 and ≥360 µmol/L, respectively, in male and female patients ≥18 years old. RESULTS: In adjusted analyses, patients with hyperuricaemia (n = 283), compared with those with normal serum uric acid, had similar 24-h systolic BP (131.7 mmHg, p = 0.54) and a significantly (p ≤ 0.005) lower 24-h diastolic BP (77.5 vs. 80.9 mmHg) and higher 24-h pulse pressure (54.2 vs. 51.7 mmHg). In similar adjusted analyses, 24-h ambulatory pulse pressure, but not systolic/diastolic BP (p ≥ 0.12), significantly differed across the quartile distributions of urinary sodium excretion (p for trend ≤ 0.04). Further adjusted analyses showed significant (p ≤ 0.04) interaction between serum uric acid and urinary sodium excretion in relation to 24-h systolic BP. In patients with hyperuricaemia (p = 0.04), but not those with normal serum uric acid (p = 0.13), 24-h systolic BP was significantly associated with urinary sodium excretion, with a 6.5 ± 2.1 mmHg difference between quartiles 4 and 1. Similar results were observed for daytime and night-time BP and pulse pressure. CONCLUSIONS: Both hyperuricaemia and higher dietary sodium intake were associated with higher pulse pressure, and their interaction further heightened systolic BP.

Human placental mesenchymal stem cells improve stroke outcomes via extracellular vesicles-mediated preservation of cerebral blood flow.

BACKGROUND: Besides long-term trans-differentiation into neural cells, benefits of stem cell therapy (SCT) in ischemic stroke may include secretion of protective factors, which partly reflects extracellular vesicle (EVs) released by stem cell. However, the mechanism(s) by which stem cells/EVs limit stroke injury have yet to be fully defined. METHODS: We evaluated the protection effect of human placenta mesenchymal stem cells (hPMSC) as a potential form of SCT in experimental ischemic stroke 'transient middle cerebral artery occusion (MCAO)/reperfusion' mice model. FINDINGS: We found for the first time that intraperitoneal administration of hPMSCs or intravenous hPMSC-derived EVs, given at the time of reperfusion, significantly protected the ipsilateral hemisphere from ischemic injury. This protection was associated with significant restoration of normal blood flow to the post-MCAO brain. More importantly, EVs derived from hPMSC promote paracrine-based protection of SCT in the MCAO model in a cholesterol/lipid-dependent manner. INTERPRETATION: Together, our results demonstrated beneficial effects of hPMSC/EVs in experimental stroke models which could permit the rapid "translation" of these cells into clinical trials in the near-term.

[Tolerance and vegetation restoration prospect of seedlings of five oak species for Pb/Zn mine tailing]. / 5ç§æ Žæ ‘å¹¼è‹—å¯¹é“ é”Œå°¾çŸ¿ç ‚çš„è€æ€§ä¸Žæ¤è¢«æ¢å¤å‰æ™¯.

A pot experiment was conducted to evaluate the growth response and vegetation restoration prospect of seedlings of five oak species for the phytoremediation of lead/zinc (Pb/Zn) mine tailings. Seedlings of Quercus imbricaria, Q. coccinea, Q. pagoda, Q. shumardii, Q. fabri were transplanted into pots containing Pb/Zn mine tailings to comparatively examine their biomass, root morphology, absorption and transfer characteristics of nutrient elements and heavy metals 30 months later. The results showed that all the seedlings could survive in the Pb/Zn tailings after 30 months. The biomass of Q. coccinea and Q. fabri decreased in Pb/Zn tailings compared with the control, while no significant difference were found for other three species. Compared with the control, root biomass was increased to some extent in Pb/Zn tailings except Q. coccinea. The lateral root morphological parameters were reduced only for Q. coccinea . Under heavy metal stress, nutrient concentrations of root and stem of oak seedlings did not change compared with the control. Generally, the concentrations of heavy metals in plant tissues were low, and the values of bioconcentration factor (BCF) and translocation factor (TF) were less than 1. Q. pagoda could accumulate more Cd, with concentrations of 22.4 and 15.1 mg·kg-1 in leaf and stem, respectively, and could translocate more Cd from root to shoot with TF of 2.3. Our results suggested that the seedlings of tested oak species could be used as the potential species for contaminated soil. Q. shumardii had the highest tole-rance with a low BCF and TF, implying that they were better potential candidates for afforestation and ecological restoration of mine tailings.

Dosage sensitivity intolerance of VIPR2 microduplication is disease causative to manifest schizophrenia-like phenotypes in a novel BAC transgenic mouse model.

Recent genome-wide association studies (GWAS) have identified copy number variations (CNVs) at chromosomal locus 7q36.3 that significantly contribute to the risk of schizophrenia, with all of the microduplications occurring within a single gene: vasoactive intestinal peptide receptor 2 (VIPR2). To confirm disease causality and translate such a genetic vulnerability into mechanistic and pathophysiological insights, we have developed a series of conditional VIPR2 bacterial artificial chromosome (BAC) transgenic mouse models of VIPR2 CNV. VIPR2 CNV mouse model recapitulates gene expression and signaling deficits seen in human CNV carriers. VIPR2 microduplication in mice elicits prominent dorsal striatal dopamine dysfunction, cognitive, sensorimotor gating, and social behavioral deficits preceded by an increase of striatal cAMP/PKA signaling and the disrupted early postnatal striatal development. Genetic removal of VIPR2 transgene expression via crossing with Drd1a-Cre BAC transgenic mice rescued the dopamine D2 receptor abnormality and multiple behavioral deficits, implicating a pathogenic role of VIPR2 overexpression in dopaminoceptive neurons. Thus, our results provide further evidence to support the GWAS studies that the dosage sensitivity intolerance of VIPR2 is disease causative to manifest schizophrenia-like dopamine, cognitive, and social behavioral deficits in mice. The conditional BAC transgenesis offers a novel strategy to model CNVs with a gain-of -copies and facilitate the genetic dissection of when/where/how the genetic vulnerabilities affect development, structure, and function of neural circuits. Our findings have important implications for therapeutic development, and the etiology-relevant mouse model provides a useful preclinical platform for drug discovery.

Transcriptome analysis of virulence-differentiated Fusarium oxysporum f. sp. cucumerinum isolates during cucumber colonisation reveals pathogenicity profiles.

BACKGROUND: Cucumber Fusarium wilt, caused by Fusarium oxysporum f. sp. cucumerinum (Foc), is one of the most notorious diseases in cucumber production. Our previous research showed the virulence of Foc significantly increases over consecutive rounds of infection in a resistant cultivar. To understand the virulence variation of Foc under host pressure, the mildly virulent strain foc-3b (WT) and its virulence-enhanced variant Ra-4 (InVir) were selected and their transcriptome profiles in infected cucumber roots were analyzed at 24 h after inoculation (hai) and 120 hai. RESULTS: A series of differentially expressed genes (DEGs) potentially involved in fungal pathogenicity and pathogenicity variation were identified and prove mainly involved in metabolic, transport, oxidation-reduction, cell wall degradation, macromolecules modification, and stress and defense. Among these DEGs, 190 up- and 360 down-regulated genes were expressed in both strains, indicating their importance in Foc infection. Besides, 286 and 366 DEGs showed up-regulated expression, while 492 and 214 showed down-regulated expression in InVir at 24 and 120 hai, respectively. These DEGs may be involved in increased virulence. Notably, transposases were more active in InVir than WT, indicating transposons may contribute to adaptive evolution. CONCLUSIONS: By a comparative transcriptome analysis of the mildly and highly virulent strains of Foc during infection of cucumber, a series of DEGs were identified that may be associated with virulence. Hence, this study provides new insight into the transcriptomic profile underlying pathogenicity and virulence differentiation of Foc.

Effects of maize rotation on the physicochemical properties and microbial communities of American ginseng cultivated soil.

The production of American ginseng (Panax quinquefolius L.) is severely limited by the replant disorders in China. Crop rotation with maize might reduce the replant problems, but little information is available on the effect of maize rotation on soil cultivated with ginseng. In this study, we analyzed nutrients, phenolic acids, and microbial communities in soils from the fields with continuous maize, mono-culture ginseng, and 1-, 3-, and 5-year maize rotation after ginseng. Pot experiments were also conducted to evaluate the performance of replanting ginseng in these soils. The results showed that Mn, Cu, and 5 phenolic acids in ginseng-cultivated soil were significantly decreased by maize rotation. A 5-year maize rotation significantly increased the relative abundance of beneficial soil bacteria, such as Arthrobacter, rather than decreasing the abundances of potential pathogenic genera. Clustering analysis revealed that the physicochemical properties and microbial communities of 3- and 5-year maize rotation soil were more similar to CM than to G soil. The biomass of replanted ginseng root was improved, and root disease was reduced over 3 years of maize rotation. Overall, the results showed that at least a 3-year maize rotation is needed to overcome the replant failure of American ginseng.

"Teaching old dogs new tricks": targeting neural extracellular matrix for normal and pathological aging-related cognitive decline.

Cognitive decline is a feature of normal and pathological aging. As the proportion of the global aged population continues to grow, it is imperative to understand the molecular and cellular substrates of cognitive aging for therapeutic discovery. This review focuses on the critical role of neural extracellular matrix in the regulation of neuroplasticity underlying learning and memory in another under-investigated "critical period": the aging process. The fascinating ideas of neural extracellular matrix forming a synaptic cradle in the tetrapartite synapse and possibly serving as a substrate for storage of very long-term memories will be introduced. We emphasize the distinct functional roles of diffusive neural extracellular matrix and perineuronal nets and the advantage of the coexistence of two structures for the adaptation to the ever-changing external and internal environments. Our study of striatal neural extracellular matrix supports the idea that chondroitin sulfate proteoglycan-associated extracellular matrix is restrictive on synaptic neuroplasticity, which plays important functional and pathogenic roles in early postnatal synaptic consolidation and aging-related cognitive decline. Therefore, the chondroitin sulfate proteoglycan-associated neural extracellular matrix can be targeted for normal and pathological aging. Future studies should focus on the cell-type specificity of neural extracellular matrix to identify the endogenous, druggable targets to restore juvenile neuroplasticity and confer a therapeutic benefit to neural circuits affected by aging.

Erasure of striatal chondroitin sulfate proteoglycan-associated extracellular matrix rescues aging-dependent decline of motor learning.

Cognitive decline is a feature of aging. Accumulating evidence suggests that the brain extracellular matrix (ECM) is involved in the process of aging-dependent cognitive impairment and neurodegeneration by regulating synaptic neurotransmission and affecting neuroplasticity. Age-related changes in brain structure and cognition are not uniform across the whole brain. Being one of the most vulnerable brain regions to aging-dependent alterations, striatum is integral to several central nervous system functions, such as motor, cognition, and affective control. However, the striatal ECM is largely understudied. We first describe 2 major types of chondroitin sulfate proteoglycan (CSPG)-associated ECM in striatum: perineuronal nets and diffusive ECM. Both types of ECM accumulate in an aging-dependent manner. The accumulation of CSPG-associated ECM correlates with aging-dependent decline in striatum-related cognitive functions, including motor learning and working memory. Enzymatic depletion of CSPG-associated ECM in aged mice via chondroitinase ABC significantly improves motor learning, suggesting that changes in neural ECM CSPGs regulate striatal plasticity. Our study provides a greater understanding of the role of neural ECM underlying striatal plasticity, which is an important precursor to design appropriate therapeutic strategies for normal and pathologic aging.

Stomaching the Possibility of a Pathogenic Role for Helicobacter pylori in Parkinson's Disease.

While a small subset of Parkinson's disease cases have genetic causes, most cases are sporadic and may have an environmental contributor that has largely remained enigmatic. Remarkably, gastrointestinal symptoms in PD patients serve as a prodrome for the eventual motor dysfunctions. Herein, we review studies exploring a possible link between the gastric human pathogen Helicobacter pylori and PD. We provide plausible and testable hypotheses for how this organism might contribute to PD: 1) a toxin(s) produced by the bacteria; 2) disruption of the intestinal microbiome; 3) local inflammation that crosses the gut-brain axis, leading to neuroinflammation; and 4) manipulation of the pharmacokinetics of the PD drug levodopa by H. pylori, even in those not receiving exogenous levodopa. Key findings are: 1) people with PD are 1.5-3-fold more likely to be infected with H. pylori than people without PD; 2) H. pylori-infected PD patients display worse motor functions than H. pylori-negative PD patients; 3) eradication of H. pylori improves motor function in PD patients over PD patients whose H. pylori was not eradicated; and 4) eradication of H. pylori improves levodopa absorption in PD patients compared to that of PD patients whose H. pylori was not eradicated. Evidence is accumulating that H. pylori has a link with PD, but the mechanism is unclear. Future work should explore the effects of H. pylori on development of PD in defined PD animal models, focusing on the roles of H. pylori toxins, inflammation, levodopa absorption, and microbiome dysbiosis.