Multi-omics explores the potential regulatory role of acetylation modification in flavonoid biosynthesis of Ginkgo biloba.

Flavonoids are crucial medicinal active ingredients in Ginkgo biloba. However, the effect of protein post-translational modifications (PTMs) on flavonoid biosynthesis remains poorly explored. Lysine acetylation, a reversible PTM, plays a crucial role in metabolic regulation. This study aims to investigate the potential role of acetylation in G. biloba flavonoid biosynthesis. Through comprehensive analysis of transcriptomes, metabolomes, proteomes, and acetylated proteins in different tissues, a total of 11,788 lysine acetylation sites were identified on 4324 acetylated proteins, including 89 acetylation sites on 23 proteins. Additionally, 128 types of differentially accumulated flavonoids were identified among tissues, and a dataset of differentially expressed genes related to the flavonoid biosynthesis pathway was constructed. Twelve (CHI, C3H1, ANR, DFR, CCoAOMT1, F3H1, F3H2, CCoAOMT2, C3H2, HCT, F3'5'H, and FG2) acetylated proteins that might be involved in flavonoid biosynthesis were identified. Specifically, we found that the modification levels of CCoAOMT1 and F3'5'H sites correlated with the catalytic production of homoeriodictyol and dihydromyricetin, respectively. Inhibitors of lysine deacetylase (trichostatin A, TSA) impacted total flavonoid content in different tissues and increased flavonoid levels in G. biloba roots. Treatment with TSA revealed that expression levels of GbF3'5'H and GbCCoAOMT1 in stems and leaves aligned with total flavonoid content variations, while in roots, expression levels of GbC3H2 and GbFG2 corresponded to total flavonoid content changes. Collectively, these findings reveal for the first time the important role of acetylation in flavonoid biosynthesis.

Gene expression prognostic of early relapse risk in low-risk B-cell acute lymphoblastic leukaemia in children.

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low-risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low-risk ETV6::RUNX1-positive B-cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome-wide transcriptome and single-nucleotide variants. We found high TIMD4 expression (> 85th-percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low-risk ETV6::RUNX1-positive B-cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low-risk ETV6::RUNX1-negative B-cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low-risk B-cell ALL in children might be associated with high risk for early relapse.

Structural characterization and therapeutic effect of Alhagi honey oligosaccharide on liver fibrosis in mice.

Alhagi honey is derived from the secretory granules of Alhagi pseudoalhagi Desv., a leguminous plant commonly known as camelthorn. Modern medical research has demonstrated that the extract of Alhagi honey possesses regulatory properties for the gastrointestinal tract and immune system, as well as exerts anti-tumor, anti-oxidative, anti-inflammatory, anti-bacterial, and hepatoprotective effects. The aim of this study was to isolate and purify oligosaccharide monomers (referred to as Mel) from camelthorn and elucidate their structural characteristics. Subsequently, the impact of Mel on liver injury induced by carbon tetrachloride (CCl4) in mice was investigated. The analysis identified the isolated oligosaccharide monomer (α-D-Glcp-(1 â†’ 3)-ß-D-Fruf-(2 â†’ 1)-α-D-Glcp), with the molecular formula C18H32O16. In a mouse model of CCl4-induced liver fibrosis, Mel demonstrated significant therapeutic effects by attenuating the development of fibrosis. Moreover, it enhanced anti-oxidant enzyme activity (glutathione peroxidase and superoxide dismutase) in liver tissues, thereby reducing oxidative stress markers (malondialdehyde and reactive oxygen species). Mel also improved serum albumin levels, lowered liver enzyme activities (aspartate aminotransferase and alanine aminotransferase), and decreased inflammatory factors (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6). Immunohistochemistry, immunofluorescence, and western blotting analyses confirmed the ability of Mel to downregulate hepatic stellate cell-specific markers (collagen type I alpha 1 chain, alpha-smooth muscle actin, transforming growth factor-beta 1. Non-targeted metabolomics analysis revealed the influence of Mel on metabolic pathways related to glutathione, niacin, pyrimidine, butyric acid, and amino acids. In conclusion, the results of our study highlight the promising potential of Mel, derived from Alhagi honey, as a viable candidate drug for treating liver fibrosis. This discovery offers a potentially advantageous option for individuals seeking natural and effective means to promote liver health.

The Ginkgo biloba microRNA160-ERF4 module participates in terpene trilactone biosynthesis.

Terpene trilactones (TTLs) are important secondary metabolites in ginkgo (Ginkgo biloba); however, their biosynthesis gene regulatory network remains unclear. Here, we isolated a G. biloba ethylene response factors 4 (GbERF4) involved in TTL synthesis. Overexpression of GbERF4 in tobacco (Nicotiana tabacum) significantly increased terpenoid content and upregulated the expression of key enzyme genes (3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), 3-hydroxy-3-methylglutaryl-CoA synthase (HMGS), 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), 1-deoxy-D-xylulose-5-phosphate synthase (DXS), acetyl-CoA C-acetyltransferase (AACT), and geranylgeranyl diphosphate synthase (GGPPS)) in the terpenoid pathway in tobacco, suggesting that GbERF4 functions in regulating the synthesis of terpenoids. The expression pattern analysis and previous microRNA (miRNA) sequencing showed that gb-miR160 negatively regulates the biosynthesis of TTLs. Transgenic experiments showed that overexpression of gb-miR160 could significantly inhibit the accumulation of terpenoids in tobacco. Targeted inhibition and dual-luciferase reporter assays confirmed that gb-miR160 targets and negatively regulates GbERF4. Transient overexpression of GbERF4 increased TTL content in G. biloba, and further transcriptome analysis revealed that DXS, HMGS, CYPs, and transcription factor genes were upregulated. In addition, yeast one-hybrid and dual-luciferase reporter assays showed that GbERF4 could bind to the promoters of the HMGS1, AACT1, DXS1, levopimaradiene synthase (LPS2), and GGPPS2 genes in the TTL biosynthesis pathway and activate their expression. In summary, this study investigated the molecular mechanism of the gb-miR160-GbERF4 regulatory module in regulating the synthesis of TTLs. It provides information for enriching the understanding of the regulatory network of TTL biosynthesis and offers important gene resources for the genetic improvement of G. biloba with high contents of TTLs.

The effects of low-dose IL-2 on Th17/Treg cell imbalance in primary biliary cholangitis mouse models.

BACKGROUND/AIMS: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The imbalance of Th17/Treg cells has been reported in PBC patients. Low-dose IL-2 can alleviate disease severity through modulating CD4 + T cell subsets in patients with autoimmune diseases. Hence, the present study aimed to examine the effects and mechanism of low-dose IL-2 in PBC mouse models. METHODS: PBC models were induced in female C57BL/6 mice by two immunizations with 2OA-BSA at two-week intervals, and poly I: C every three days. PBC mouse models were divided into the IL-2 treated and untreated groups and low-dose IL-2 was injected at three different time points. Th17 and Tregs were analyzed by flow cytometry, and the related cytokines were analyzed by ELISA. Liver histopathology was examined by H&E and immunohistochemical staining. RESULTS: Twelve weeks after modeling, the serum AMA was positive and the ALP was significantly increased in PBC mouse models (P<0.05). The pathology showed lymphocyte infiltration in the portal area, damage, and reactive proliferation of the small bile duct (P<0.05). The flow cytometric showed the imbalance of Th17/Treg cells in the liver of PBC mouse models, with decreased Treg cells, increased Th17 cells, and Th17/Treg ratio (P < 0.05). After the low-dose IL-2 intervention, biochemical index and liver pathologies showed improvement at 12 weeks. Besides, the imbalance of Th17 and Treg cells recovered. Public database mining showed that Th17 cell differentiation may contribute to poor response in PBC patients. CONCLUSION: Low-dose IL-2 can significantly improve liver biochemistry and pathology by reversing the imbalance of Th17 and Treg cells, suggesting that it may be a potential therapeutic target for PBC.

Donor-derived cell-free DNA as a diagnostic marker for kidney-allograft rejection: A systematic review and meta-analysis.

Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising biomarker for detecting graft rejection. This study aimed to evaluate the diagnostic accuracy and clinical value of applying it to kidney transplant rejection. Relevant literature on dd-cfDNA diagnostics in kidney transplant rejection was reviewed from PubMed, Embase, Cochrane Library, and Web of Science databases up to 2023. Data and study characteristics were extracted independently by two researchers, and disagreements were resolved through discussion. Diagnostic accuracy data for any rejection (AR) and antibody-mediated rejection (ABMR) were analyzed separately. Potential heterogeneity was analyzed by subgroup analysis or meta-regression. Funnel plots were used to clarify the presence or absence of publication bias. Nine publications provided data on dd-cfDNA accuracy in diagnosing patients with AR. The pooled sensitivity, specificity, and the area under the receiver operating characteristic (AUROC) curve with 95% confidence intervals (CI) were 0.59 (95% CI, 0.48-0.69), 0.83 (95% CI, 0.76-0.88), and 0.80 (95% CI, 0.76-0.83), respectively. Additionally, 12 studies focused on the diagnostic accuracy of dd-cfDNA for ABMR, showing pooled sensitivity, specificity, and the AUROC curve with 95% CI of 0.81 (95% CI, 0.72-0.88), 0.80 (95% CI, 0.73-0.86), and 0.87 (95% CI, 0.84-0.90), respectively. Study type, age group, and sample size contributed to heterogeneity. In summary, our findings indicate that while plasma dd-cfDNA accuracy in diagnosing patients with AR is limited by significant heterogeneity, it is a valuable biomarker for diagnosing ABMR.

eALT-F: A New Non-Invasive Staging Method to Identify Medium to High-Risk Patients with HCC from Ultra-High HBV Viral Load Population - China, 2010-2023.

Background: The objective of this study was to examine the clinical characteristics of individuals with ultra-high hepatitis B virus (HBV) viral load and develop a novel staging method for chronic hepatitis B (CHB) that can more effectively identify patients with medium to high hepatocellular carcinoma (HCC) risk. Methods: A total of 2,118 patients with HBV DNA >1×107 IU/mL who visited Peking University People's Hospital between January 2010 and March 2023 were enrolled retrospectively. Clinical data from the first visit were obtained and analyzed. The traditional phases and new 'eALT-F' stages were compared to evaluate the risk of HCC. Results: In the overall patients, more than one-third of the patients were under 30 years old. Additionally, a small proportion of older people (>60 years) also had ultra-high HBV viral load (4.3%). 9.1% and 6.7% of individuals with ultra-high HBV viral load showed FIB-4>3.25 and aMAP≥50, respectively. In the traditional stages of CHB, which are based on HBeAg and alanine aminotransferase (ALT) [the upper limit of normal (ULN) ALT level at 40 IU/L for both men and women], regardless of phase, a certain proportion of patients were at risk of developing HCC (4.1%, 6.4%, 25.0%, and 20.3%). However, in the new 'eALT-F' stages, which are based on HBeAg, ALT (the ULN of ALT level at 30 IU/L for men and 19 IU/L for women), and/or FIB-4 levels (>1.45), aMAP≥50 was only observed in chronic hepatitis patients with positive or negative HBeAg (6.4% and 22.1%, respectively). Conclusions: The 'eALT-F' staging method, based on HBeAg, ALT (males: the ULN of ALT was 30 IU/L, females: 19 IU/L) and/or FIB-4 levels, was more effective in identifying medium to high-risk patients with HCC from patients with ultra-high HBV viral load than the traditional staging methods.

Multiomics analysis provides new insights into the regulatory mechanism of carotenoid biosynthesis in yellow peach peel.

Carotenoids, as natural tetraterpenes, play a pivotal role in the yellow coloration of peaches and contribute to human dietary health. Despite a relatively clear understanding of the carotenoid biosynthesis pathway, the regulatory mechanism of miRNAs involved in carotenoid synthesis in yellow peaches remain poorly elucidated. This study investigated a total of 14 carotenoids and 40 xanthophyll lipids, including six differentially accumulated carotenoids: violaxanthin, neoxanthin, lutein, zeaxanthin, cryptoxanthin, and (E/Z)-phytoene. An integrated analysis of RNA-seq, miRNA-seq and degradome sequencing revealed that miRNAs could modulate structural genes such as PSY2, CRTISO, ZDS1, CHYB, VDE, ZEP, NCED1, NCED3 and the transcription factors NAC, ARF, WRKY, MYB, and bZIP, thereby participating in carotenoid biosynthesis and metabolism. The authenticity of miRNAs and target gene was corroborated through quantitative real-time PCR. Moreover, through weighted gene coexpression network analysis and a phylogenetic evolutionary study, coexpressed genes and MYB transcription factors potentially implicated in carotenoid synthesis were identified. The results of transient expression experiments indicated that mdm-miR858 inhibited the expression of PpMYB9 through targeted cleavage. Building upon these findings, a regulatory network governing miRNA-mediated carotenoid synthesis was proposed. In summary, this study comprehensively identified miRNAs engaged in carotenoid biosynthesis and their putative target genes, thus enhancing the understanding of carotenoid accumulation and regulatory mechanism in yellow peach peel and expanding the gene regulatory network of carotenoid synthesis.

Quantitative susceptibility mapping in rats with minimal hepatic encephalopathy: Does iron overload aggravate cognitive impairment by promoting neuroinflammation?

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a mild form of hepatic encephalopathy that lacks observable signs and symptoms. Nevertheless, MHE can cause neurocognitive dysfunction, although the neurobiological mechanisms are not fully understood. Here, the effects of hippocampal iron deposition on cognitive function and its role in MHE were investigated. MATERIALS AND METHODS: Eighteen rats were assigned to experimental and control groups. MHE was induced by thioacetamide. Spatial memory and exploratory behavior were assessed by the Morris water and elevated plus mazes. Hippocampal susceptibility was measured by quantitative susceptibility mapping, iron deposition in the hippocampus and liver by Prussian blue staining, and inflammatory cytokine and ferritin levels in the hippocampus were measured by ELISA. RESULTS: MHE rats showed impaired spatial memory and exploratory behavior (P < 0.05 for all parameters). The bilateral hippocampal susceptibility values were significantly raised in MHE rats, together with evidence of neuroinflammation (increased pro-inflammatory and reduced anti-inflammatory cytokine levels (all P < 0.05). Further analysis indicated good correlations between hippocampal susceptibility values with latency time and inflammatory cytokine levels in MHE but not in control rats. CONCLUSION: MHE induced by thioacetamide was associated with hippocampal iron deposition and inflammation, suggesting that iron overload may be an important driver of neuroinflammatory responses.

Tracking progress towards equitable maternal and child health in Yunnan: a systematic assessment for the Health Programme for Poverty Alleviation in China during 2015-2020.

OBJECTIVES: To inform the impacts of health programmes which aimed at preventing women and children from being trapped in or returning to poverty because of illness in Yunnan, the main battlefield against poverty in China. DESIGN: The longitudinal comparative evaluation design. DATA COLLECTION AND ANALYSIS: National and Yunnan policy documents related to maternal and child health programmes for poverty alleviation during 2015-2020 were analysed. The changes in disparities in maternal and child health system inputs, service coverage, and health outcomes between poor and non-poor areas, as well as out-of-pocket payments between poor and non-poor populations were assessed before and after 2017. RESULTS: In total 12 policies and 15 programmes related to poverty alleviation for poor women and children in Yunnan were summarised. As a result of health system strengthening in Yunnan, the densities of licensed doctors, nurses, obstetricians, midwives, township health workers and female village doctors had been increased substantially in poor areas, with the annual rates of 14.3%, 22.5%, 21.8%, 23.9%, 14.1% and 7.1% separately. Although disparities existed in some of service coverage between poor and non-poor areas, the health programmes had narrowed the gaps in utilisation of facility birth, caesarean section, prenatal screening and newborn screening across Yunnan (p<0.01). The out-of-pocket payments for inpatient care for serious illnesses among women and children with poverty registration had been considerably decreased to 10.0%. Paralleling the universal coverage, maternal deaths per 100 000 livebirths and child deaths per 1000 livebirths had further declined in both poor and non-poor areas, and the impacts of health programmes on closing the gaps in child survivals across Yunnan were significant (p<0.01). CONCLUSIONS: Remarkable progress in equitable maternal and child survival has been achieved in Yunnan. The practices in Yunnan have shown the Chinese model in ending poverty by strengthening health system and implementing universal coverage with firm commitment, determined leadership, detailed blueprint and social participation.

Lower alanine aminotransferase levels are associated with increased all-cause and cardiovascular mortality in nonalcoholic fatty liver patients.

BACKGROUND: Serum alanine aminotransferase (ALT) levels are often considered a marker to evaluate liver disease and its severity. AIM: To investigate the association between ALT levels and all-cause and cause-specific mortality in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: The Third National Health and Nutrition Examination Survey (NHANES-III) from 1988 to 1994 and NHANES-III-related mortality data from 2019 onward were used to obtain the necessary data for the study. NAFLD was defined as hepatic steatosis, as diagnosed by ultrasound, with no other liver diseases. ALT levels were categorized into four groups according to the different recommended upper limits of normal (ULN) in men and women: < 0.5 ULN, 0.5-1 ULN, 1-2 ULN, and ≥ 2 ULN. The hazard ratios for all-cause mortality and cause-specific mortality were analyzed using the Cox proportional hazard model. RESULTS: Multivariate logistic regression analysis demonstrated that the odds ratio of NAFLD correlated positively with increased serum ALT levels. In patients with NAFLD, all-cause mortality and cardiovascular mortality were the highest when ALT was < 0.5 ULN, yet cancer-related mortality was the highest when ALT was ≥ 2 ULN. The same results could be found in both men and women. Univariate analysis showed that severe NAFLD with normal ALT levels had the highest all-cause and cause-specific mortality, but the difference was not statistically significant after adjustment for age and multivariate factors. CONCLUSION: The risk of NAFLD was positively correlated with ALT level, but all-cause and cardiovascular mortality were the highest when ALT was < 0.5 ULN. Regardless of the severity of NAFLD, normal or lower ALT levels were associated with higher mortality than elevated ALT levels. Clinicians should be aware that high ALT levels indicate liver injury, but low ALT levels are associated with a higher risk of death.

Pan-HDAC inhibitors augment IL2-induced proliferation of NK cells via the JAK2-STAT5B signaling pathway.

BACKGROUND: Natural killer (NK) cells are a subtype of lymphocytes with the ability to quickly and efficiently identify and eliminate tumor cells. In the presence of IL2, NK cells can divide rapidly but in limited numbers. According to previous studies, in vivo treatment with histone deacetylase (HDAC) inhibitors did not impair NK-cell function. This study aimed to investigate the effect of HDAC inhibitors on NK-cell proliferation and the underlying regulatory mechanism. METHODS: NK92 cells, primary NK (pNK) cells, and CD19-CAR-NK92 cells were treated with low concentrations of pan-HDACi Dacinostat (Dac) and Panobinostat (Pan) in the presence of IL2, and Cell Counting Kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays were used to assess cell proliferation and apoptosis. The expression of granzyme B was detected by immunofluorescence, and the expression of CD107a and NKG2D was determined by flow cytometry. The downstream regulatory genes were identified by RNA-seq, and the "JAK-STAT signaling pathway"- and "Cell cycle signaling pathway"-related genes were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. The JAK2V617F mouse model was constructed to simulate the upregulation of the JAK2 signaling pathway in vivo, and the NK proliferation was evaluated by flow cytometry. A tumor-bearing nude mouse model was constructed to determine the anti-tumor efficacy of NK92 cells following Dac treatment. RESULTS: In the presence of IL2, the proliferation rate of NK92 cells, pNK cells, and CD19-CAR-NK92 cells treated with pan-HDACi Dac and Pan at low nanomolar doses was significantly increased, although cell function was unaffected. Low doses of Dac upregulated the JAK-STAT signaling pathway and enhance the cell cycle via that pathway. In addition, the in vivo experiment in nude mice showed that the capacity of Dac treated NK92 cells to eliminate tumor cells was unaffected. CONCLUSION: Low nanomolar doses of Pan-HDACi enhanced IL2-induced NK cell proliferation without compromising the functioning of NK cells.

An Ideal Hallmark Closest to Complete Cure of Chronic Hepatitis B Patients: High-sensitivity Quantitative HBsAg Loss.

In the era of antiviral therapy, the main goal of treatment has shifted from the persistent inhibition of hepatitis B virus (HBV) replication to the pursuit of serological clearance of HBs surface antigen (HBsAg). Based on the life cycle of HBV, HBsAg originates from covalently closed circular DNA (cccDNA) and integrated HBV DNA, thus reflecting their transcriptional activity. Complete HBsAg loss may mean elimination or persistent inactivity of the HBV genome including cccDNA and integrated HBV DNA. HBsAg loss improves the recovery of abnormal immune function, which in turn, may further promote the clearance of residual viruses. Combined with functional cure and the great improvement of clinical outcomes, the continuous seroclearance of high-sensitivity quantitative HBsAg may represent the complete cure of chronic hepatitis B (CHB). For many other risk factors besides HBV itself, patients with HBsAg loss still need regular monitoring. In this review, we summarized the evolution of CHB treatment, the origin of serum HBsAg, the pattern of HBsAg seroclearance, and the effect of HBsAg loss on immune function and disease outcomes. In addition, we discuss the significance of high-sensitivity HBsAg detection and its possibility as a surrogate of complete cure.

Hepatitis B functional cure and immune response.

Hepatitis B virus (HBV) is a hepatotropic virus, which damage to hepatocytes is not direct, but through the immune system. HBV specific CD4+ T cells can induce HBV specific B cells and CD8+ T cells. HBV specific B cells produce antibodies to control HBV infection, while HBV specific CD8+ T cells destroy infected hepatocytes. One of the reasons for the chronicity of HBV infection is that it cannot effectively activate adoptive immunity and the function of virus specific immune cells is exhausted. Among them, virus antigens (including HBV surface antigen, e antigen, core antigen, etc.) can inhibit the function of immune cells and induce immune tolerance. Long term nucleos(t)ide analogues (NAs) treatment and inactive HBsAg carriers with low HBsAg level may "wake up" immune cells with abnormal function due to the decrease of viral antigen level in blood and liver, and the specific immune function of HBV will recover to a certain extent, thus becoming the "dominant population" for functional cure. In turn, the functional cure will further promote the recovery of HBV specific immune function, which is also the theoretical basis for complete cure of hepatitis B. In the future, the complete cure of chronic HBV infection must be the combination of three drugs: inhibiting virus replication, reducing surface antigen levels and specific immune regulation, among which specific immunotherapy is indispensable. Here we review the relationship, mechanism and clinical significance between the cure of hepatitis B and immune system.

[Neuropsychological development of human immunodeficiency virus-exposed uninfected infants/young children]. / äººç±»å ç–«ç¼ºé™·ç— æ¯’æš´éœ²æœªæ„ŸæŸ“å©´å¹¼å„¿çš„ç¥žç»å¿ƒç†å‘è‚²çŠ¶å†µ.

OBJECTIVES: To investigate the level of neuropsychological development in human immunodeficiency virus (HIV)-exposed uninfected (HEU) infants/young children and the influence of maternal HIV infection on the neuropsychological development of HEU infants/young children. METHODS: A total of 141 HEU infants/young children, aged 0-18 months and born to HIV-infected mothers, who were managed in four maternal and child health care hospitals in Yunnan Province of China from June 2019 to December 2020 and met the inclusion criteria were enrolled as the HEU group. A total of 141 HIV-unexposed uninfected (HUU) infants/young children who were born to healthy mothers and managed in the same hospitals, matched at a ratio of 1:1 based on sex, age, method of birth, birth weight, and gestational age, were enrolled as controls. Griffiths Development Scales-Chinese Edition was used to assess the development in the five domains of locomotion, personal-social, hearing and language, eye-hand co-ordination, and performance (visual perception and space integration ability). A questionnaire survey was performed to collect relevant information. The multivariate logistic regression analysis was used to assess the influence of maternal HIV infection on the neuropsychological development of HEU infants/young children. RESULTS: Compared with the HUU group, the HEU group had significantly higher detection rates of retardation in the domains of hearing and language and performance (P<0.05). The multivariate logistic regression analysis showed that maternal HIV infection increased the risk of retardation in the domains of hearing and language (OR=2.661, 95%CI: 1.171-6.047, P<0.05) and performance (OR=2.321, 95%CI: 1.156-4.658, P<0.05). CONCLUSIONS: Maternal HIV infection can negatively affect the development of hearing and language and performance in HEU infants/young children, and further studies are needed to clarify related mechanisms.

Decreased brain noradrenaline in minimal hepatic encephalopathy is associated with cognitive impairment in rats.

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a common neuropsychiatric complication in patients with cirrhosis. Alterations in monoamine neurotransmitters have been associated with the pathogenesis of MHE. We investigated the levels of hippocampal noradrenergic neurotransmitter in a rat model of thioacetamide-induced chronic liver failure-related MHE, and their role in cognitive impairment. MATERIALS: 18 male Sprague-Dawley (SD) rats were equally divided in MHE and control groups. A rat model of MHE was established by intraperitoneal injection of thioacetamide (TAA) for 12 weeks. Cognitive function was assessed using the Morris water maze (MWM) test and locomotor activity and exploratory behavior assessed with open field test. The concentration of hippocampal noradrenaline (NE) was detected by ELISA, and the magnetic susceptibility value in the hippocampus was detected by quantitative susceptibility mapping. Hippocampal iron content was quantified by Prussian blue staining. RESULTS: MHE rats performed significantly poorer than their control counterparts in the MWM test, as seen by decreased number of platform crossings and time in the target quadrant, and increased path length to reach the target zone (P < 0.05 for all parameters). In the open field test, the MHE group exhibited lower locomotor activity and exploratory behavior than the control group (P < 0.05 for all parameters). We detected pronounced iron staining in the hippocampus of MHE rats, whereas no iron-stained particles were found in control rats. We observed an imbalance of inflammatory (increased pro- and decreased anti-) cytokines in the hippocampus of MHE rats. Further analysis of the data showed that the level of hippocampal noradrenaline in MHE rats was significantly lower than that of control rats (P < 0.05). We observed a correlation between the level of inflammatory cytokine and noradrenaline land susceptibility value in the rat hippocampus of the MHE group. CONCLUSION: Our results suggest that MHE associated with TAA-induced chronic liver failure is associated with alterations in noradrenergic neurotransmission. We propose that iron imbalance in the brain might lead to reduction in the levels of noradrenaline, and cognitive impairment.

Trends in the psychosocial and mental health of HIV-positive women in China from 2015 to 2020: Results from two cross-sectional surveys.

BACKGROUND: The human immunodeficiency virus (HIV) continues to be one of the major public health challenges in the world. Despite the advancement in medication and changes in views towards HIV in Chinese society, little is known about the changes in the psychosocial and mental health of HIV-positive women in recent years. OBJECTIVES: The present study examined the change in depression, anxiety, stigma, relationship with the child, intimacy with a partner, and social support from family, friends, and health professionals, for HIV-positive women in China from 2015 to 2020. METHODS: Two cross-sectional surveys were conducted in 2015 and 2020, and 429 and 382 HIV-positive women were recruited from the Women's Health Department in Yunnan and Guangxi, China between November 2015 to May 2016, and November 2019 to January 2020, respectively. RESULTS: After controlling for significant sociodemographic variables, participants recruited in 2019-2020 had significantly lower levels of depression and anxiety and higher scores on emotional and tangible support from friends. On the other hand, they had lower scores in intimacy with partners and emotional and tangible support from family. No significant changes were found in stigma, relationship with the child, and support from health professionals. CONCLUSION: Results provide important information on the changes in psychosocial and mental health, which offer insights into the design of interventions to promote psychosocial and mental health among HIV-positive women in China. PATIENT OR PUBLIC CONTRIBUTION: HIV-positive women contributed to the data of this study. Health care professionals were involved in the discussion of the methods and results.

Transcriptome and miRNA sequencing analyses reveal the regulatory mechanism of α-linolenic acid biosynthesis in Paeonia rockii.

Paeonia rockii is a promising woody oil crop because its seeds are rich in polyunsaturated fatty acids especially α-linolenic acid (ALA). ALA is an essential fatty acid that the human body cannot synthesize and is the direct synthetic precursor of eicosapentaenoic and docosahexaenoic acids, which play crucial roles in the development of the blood vessels, brain and nervous system of humans. However, the mechanisms underlying the dynamic changes in ALA during seed development are unknown. In this study, we found that the fatty acid content gradually increased with P. rockii seed development, with ALA being the main unsaturated acid component (37-44%). The content of ALA reached the peak value of 306.26 mg/g DW 20 days before the seeds had fully maturated. Seeds from three different developmental stages were selected for transcriptome and miRNA sequencing analyses to explore the molecular mechanism of ALA accumulation in P. rockii seeds. A total of 39 differentially expressed genes were screened for their involvement in ALA biosynthesis, among which FAD2/8, GPAT, PDAT, LACS, LPAAT, and KAS II might be the key structural genes of ALA accumulation. The differential expression of these genes was dependent on the regulation of five miRNAs (mdm_miR156b, novel miR_91, novel miR_133, novel miR_291, and novel miR_405) and four transcription factors (AP2, SNL2, TGA-like, and SPL). This study reveals the mechanism behind the dynamic changes of ALA contents in P. rockii during seed development, and also provides an important theoretical basis for the breeding of excellent varieties of P. rockii.

Diversity and Phosphate Solubilizing Characteristics of Cultivable Organophosphorus-Mineralizing Bacteria in the Sediments of Sancha Lake.

The organophosphate-mineralizing bacteria (OPB) convert environmental organic phosphorus (P) into soluble P that can be directly absorbed and utilized by organisms. OPB is an important group of microorganisms in lake sediments. The P decomposed and released from the sediments by OPB is an important P-source in eutrophic water bodies. In this study, the egg-yolk organophosphate medium was used to isolate and screen OPB strains from the sediments of Sancha Lake. Furthermore, the obtained OPB strains were classified based on their 16S rDNA sequence. Both the solid and liquid lecithin hydrolyzing experiments were conducted to investigate the P-solubilizing characteristics of the obtained OPB strains. Microcosm experimentsiwere performed to study the P-release ability of OPB strains from sediments. A total of 39 OPB strains were isolated from the sediments of Sancha Lake. They belonged to three phyla, five families, and five genera, and contained two potentially new species. Bacillus and Pseudomonas were the dominant genera. On the solid lecithin plate, 35 of the 39 OPB strains produced visible phosphate halos, and 24 strains showed a high ratio of P halo diameter (HD)/colony diameter (CD). In the liquid lecithin medium, all 39 OPB strains demonstrated P-solubilizing ability, but with significant differences. The Pseudomonas strain demonstrated the strongest P-solubilizing ability, at 70.91 mg·L-1. There was no significant correlation between the amount of released phosphorus by OPB strains and pH. The P-solubilizing characteristics of OPB were affected by the interaction of dissolved inorganic phosphate and alkaline phosphatase. In the microcosm experiments, the added OPB strains significantly promoted the decomposition and release of organic phosphorus (OP) in the sediments. OPB in the sediments of Sancha Lake is rich in diversity and had a strong ability to release OP in the sediments.