Chromosome structure modeling tools and their evaluation in bacteria.

The three-dimensional (3D) structure of bacterial chromosomes is crucial for understanding chromosome function. With the growing availability of high-throughput chromosome conformation capture (3C/Hi-C) data, the 3D structure reconstruction algorithms have become powerful tools to study bacterial chromosome structure and function. It is highly desired to have a recommendation on the chromosome structure reconstruction tools to facilitate the prokaryotic 3D genomics. In this work, we review existing chromosome 3D structure reconstruction algorithms and classify them based on their underlying computational models into two categories: constraint-based modeling and thermodynamics-based modeling. We briefly compare these algorithms utilizing 3C/Hi-C datasets and fluorescence microscopy data obtained from Escherichia coli and Caulobacter crescentus, as well as simulated datasets. We discuss current challenges in the 3D reconstruction algorithms for bacterial chromosomes, primarily focusing on software usability. Finally, we briefly prospect future research directions for bacterial chromosome structure reconstruction algorithms.

Complement C1q/C3-CR3 signaling pathway mediates abnormal microglial phagocytosis of synapses in a mouse model of depression.

BACKGROUND: Both functional brain imaging studies and autopsy reports have indicated the presence of synaptic loss in the brains of depressed patients. The activated microglia may dysfunctionally engulf neuronal synapses, leading to synaptic loss and behavioral impairments in depression. However, the mechanisms of microglial-synaptic interaction under depressive conditions remain unclear. METHODS: We utilized lipopolysaccharide (LPS) to induce a mouse model of depression, examining the effects of LPS on behaviors, synapses, microglia, microglial phagocytosis of synapses, and the C1q/C3-CR3 complement signaling pathway. Additionally, a C1q neutralizing antibody was employed to inhibit the C1q/C3-CR3 signaling pathway and assess its impact on microglial phagocytosis of synapses and behaviors in the mice. RESULTS: LPS administration resulted in depressive and anxiety-like behaviors, synaptic loss, and abnormal microglial phagocytosis of synapses in the hippocampal dentate gyrus (DG) of mice. We found that the C1q/C3-CR3 signaling pathway plays a crucial role in this abnormal microglial activity. Treatment with the C1q neutralizing antibody moderated the C1q/C3-CR3 pathway, leading to a decrease in abnormal microglial phagocytosis, reduced synaptic loss, and improved behavioral impairments in the mice. CONCLUSIONS: The study suggests that the C1q/C3-CR3 complement signaling pathway, which mediates abnormal microglial phagocytosis of synapses, presents a novel potential therapeutic target for depression treatment.

Ionic Liquids-Driven Cluster-to-Cluster Conversion of Polyhydrido Copper(I) Clusters Cu7H5 to Cu8H6 and Cu12H9.

Although ionic liquids (ILs) are of prime interest for the synthesis of various nanomaterials, they are scarcely utilized for the polyhydrido copper(I) [Cu(I)H] clusters. Herein, two air-stable Cu(I)H clusters, [Cu8H6(dppy)6](NTf2)2 (Cu8H6) and {Cu12H9(dppy)6[N(CN)2]3} (Cu12H9), are synthesized in high yields for the first time from the ILs-driven conversion of an unprecedented cluster [Cu7H5(dppy)6](ClO4)2 (Cu7H5) by a facile three-layers diffusion crystal (TLDC) method, strategically introducing IL-NTf2 and IL-N(CN)2 as two types of unusual interfacial crystallized templates, respectively. Their structures are fully characterized by various spectroscopic methods and X-ray crystallography, which shows that the anion of IL plays an important role as an anion template and an anion ligand in controlling the structural conversion of Cu(I)H clusters. Their photophysical properties are also investigated, and it is found that all reported clusters exhibit red luminescence with λem ranging from 600 to 690 nm.

Myocardial Work for Dynamic Monitoring of Myocardial Injury in Neonatal Asphyxia.

To assess the value of parameters of myocardial work for dynamic monitoring of myocardial injury after neonatal asphyxia. Fifty-three neonates with asphyxia admitted within 24 h after delivery were divided into a mild asphyxia group (n = 40) and severe asphyxia group (n = 13). Echocardiography was performed within 24 h post-birth, within 72 h post-birth (48 h after first echo), and during recovery. The left ventricular ejection fraction on M-mode echocardiography and by Simpson's biplane method (LVEF and Bi-EF, respectively), stroke volume (SV), cardiac output (CO), cardiac index (CI), global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), and other parameters were measured. Echocardiographic indicators were compared between groups and over time. GWI was significantly increased at 72 h in the mild asphyxia group (P < 0.05) but showed no significant change over time in the severe asphyxia group (P > 0.05). While GCW increased significantly over time in both groups (P < 0.05), it increased earlier in the mild asphyxia group. Time and grouping factors had independent effects on GWI and GCW (P > 0.05). The characteristics of differences in GWI and GCW between the two groups were different from those for LVEF, Bi-EF, SV, CO, CI, and GLS and their change characteristics with improvement from treatment. GWI and GCW changed significantly during recovery from neonatal asphyxia, and their change characteristics differed between mild and severe asphyxia cases. Myocardial work parameters can be used as valuable supplements to traditional indicators of left ventricular function to dynamically monitor the recovery from myocardial injury after neonatal asphyxia.

Independent Component Analysis Reveals the Transcriptional Regulatory Modules in Bradyrhizobium diazoefficiens USDA110.

The dynamic adaptation of bacteria to environmental changes is achieved through the coordinated expression of many genes, which constitutes a transcriptional regulatory network (TRN). Bradyrhizobium diazoefficiens USDA110 is an important model strain for the study of symbiotic nitrogen fixation (SNF), and its SNF ability largely depends on the TRN. In this study, independent component analysis was applied to 226 high-quality gene expression profiles of B. diazoefficiens USDA110 microarray datasets, from which 64 iModulons were identified. Using these iModulons and their condition-specific activity levels, we (1) provided new insights into the connection between the FixLJ-FixK2-FixK1 regulatory cascade and quorum sensing, (2) discovered the independence of the FixLJ-FixK2-FixK1 and NifA/RpoN regulatory cascades in response to oxygen, (3) identified the FixLJ-FixK2 cascade as a mediator connecting the FixK2-2 iModulon and the Phenylalanine iModulon, (4) described the differential activation of iModulons in B. diazoefficiens USDA110 under different environmental conditions, and (5) proposed a notion of active-TRN based on the changes in iModulon activity to better illustrate the relationship between gene regulation and environmental condition. In sum, this research offered an iModulon-based TRN for B. diazoefficiens USDA110, which formed a foundation for comprehensively understanding the intricate transcriptional regulation during SNF.

The neuroprotective effects of GPR55 against hippocampal neuroinflammation and impaired adult neurogenesis in CSDS mice.

Depression is one of the most prevalent mental illnesses in the world today, and the onset of depression is usually accompanied by neuroinflammation and impaired adult neurogenesis. As a new potential member of the endocannabinoid (eCB) system, G protein coupled receptor 55 (GPR55) has been associated with mood regulation. However, the role of GPR55 in the pathophysiology of depression remains poorly understood. Thus, a 10-day chronic social defeat stress (CSDS) paradigm was utilized as an animal model of depression to explore the potential role of GPR55 in depression. After CSDS, the protein level of GPR55 decreased significantly, but the mRNA expression did not change significantly, highlighting that although the GPR55 protein was involved in the progression of the depression- and anxiety-like phenotypes, its mRNA was not. Additionally, depression- and anxiety-like behaviors were also accompanied by neuroinflammation and impaired adult neurogenesis in the hippocampus. Interestingly, O-1602, a GPR55 agonist, remarkably prevented the development of depression- and anxiety-like behaviors as well as hippocampal neuroinflammation and neurogenesis deficits induced by CSDS. However, after electroacupuncture (EA) alleviated depression- and anxiety-like behaviors induced by CSDS, treatment with a GPR55 antagonist (CID16020046) reversed this effect. Our research demonstrated that downregulation of GPR55 expression in the hippocampus might mediate CSDS-induced depression- and anxiety-like phenotypes, and activation and upregulation of GPR55, which might be correlated with its anti-inflammatory and subsequent neuroprotective effects, could be a potential treatment for depression.

Spectrum-effect relationship between hplc fingerprint and anti-inflammatory activity of n-butanol parts of Tetrastigma planicaule (Hook) Gagnep.

The present study aimed to evaluate the spectrum-effect relationships between high-performance liquid chromatography fingerprints and anti-inflammatory effects of Tetrastigma planicaule(Hook.)Gagnep. Chemical fingerprints of ten batches of Tetrastigma planicaule from various sources were obtained by HPLC. The anti-inflammatory activity was investigated by a model of ear swelling in mice caused by xylene and a model of cotton pellet granuloma. Hierarchical cluster analysis (HCA) results showed that all the samples were clustered into four categories, which was basically consistent with the principal component analysis (PCA) results. The results of the joint grey relational analysis (GRA) and partial least squares regression analysis (PLSR) showed that peaks 1, 2 and 12 were positively correlated with the anti-acute inflammatory effect (ear swelling) in mice, and peaks 3, 5, 6 and 11 were positively correlated with the anti-chronic inflammatory effect (cotton pellet granuloma) in mice. The anti-inflammatory effect of Tetrastigma planicaule is the result of the synergistic effect of multiple components, which provides a basis for further exploring the anti-inflammatory substances and quality evaluation of the herb.

Assessment of myocardial injury in neonates born to pregnant women with pregnancy complicated by severe preeclampsia by myocardial work indices: a prospective study. / å¿ƒè‚ŒåšåŠŸå‚æ•°è¯„ä¼°é‡åº¦å­ç—«å‰æœŸå­•å¦‡å­ä»£æ–°ç”Ÿå„¿æœŸå¿ƒè‚ŒæŸä¼¤çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To evaluate myocardial injury in neonates born to pregnant women with pregnancy complicated by severe preeclampsia by myocardial work indices. METHODS: A prospective cohort study was performed on 25 preterm infants born to the pregnant women with severe preeclampsia from June 2020 to April 2021 (severe preeclampsia group), and 25 preterm infants born to the pregnant women without severe complications in pregnancy were enrolled as the control group. Echocardiography was performed within 24 hours and at 48-72 hours and 14-28 days after birth to measure conventional parameters. Two-dimensional speckle-tracking echocardiography was performed to construct a noninvasive left ventricular pressure-strain loop based on two-dimensional myocardial strain and left ventricular systolic pressure noninvasively measured, so as to calculate myocardial work indices. RESULTS: Compared with the control group, the severe preeclampsia group had significant reductions in left ventricular global work index and global constructive work within 24 hours after birth (P<0.05), a significant reduction in left ventricular global work efficiency and a significant increase in global waste work at 48-72 hours after birth (P<0.05), and a significant reduction in left ventricular global work efficiency at 14-28 days after birth (P<0.05). CONCLUSIONS: Subclinical myocardial injury persists in the neonatal period in preterm infants born to pregnant women with severe preeclampsia.

Ultrasonography to detect cardiovascular damage in children with essential hypertension.

BACKGROUND: Essential hypertension in adults may begin in childhood. The damages to the heart and blood vessels in children with essential hypertension are hidden and difficult to detect. We noninvasively examined changes in cardiovascular structure and function in children with hypertension at early stage using ultrasonography. METHODS: All patients with essential hypertension admitted from March 2020 to May 2021 were classified into simple hypertension (group 1, n = 34) and hypertension co-existing with obesity (group 2, n = 11) isolation. Meanwhile 32 healthy children were detected as control heathly group (group 3). We used pulse-wave Doppler to measure carotid-femoral pulse wave velocity (cfPWV), intimal-medial thickness (cIMT) and distensibility of carotid artery (CD). Cardiac structure and function (left atrial diameter [LAD], left ventricular mass [LVM], LVM index [LVMI], relative wall thicknes [RWT], end-diastolic left ventricular internal diameter [LVIDd], diastolic interventricular septum thickness [IVSd], diastolic left ventricular posterior wall thickness [LVPWd], root diameter of aorta [AO], E peak, A peak, E' peak, A' peak, E/E' ratio, and E/A ratio) were measured by echocardiography. RESULTS: The cfPWV of children in group 1 and group 2 were significantly higher than healthy children in group 3. Significant differences were observed in LVM, LVMI, RWT, LVIDd, IVSd, LVPWd, LAD, A peak, E' peak, A' peak, and E/E' among three groups. CONCLUSION: Children and adolescents with essential hypertension demonstrate target organ damages in the heart and blood vessels.

Fish consumption, long-chain omega-3 fatty acids intake and risk of stroke: An updated systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Although fish consumption or omega-3 intake is associated with cardio- cerebrovascular disease including stroke, their correlation is still controversial. Therefore, this meta-analysis is to identify the relationship between the risk of stroke and fish consumption or omega-3 intake. METHODS AND STUDY DESIGN: We searched the PubMed, EMBASE and Cochrane Library databases as of May 2019. Multivariateadjusted risk ratios (RRs) with 95% confidence interval (CI) for stroke in different level intake of fish or Longchain omega-3 polyunsaturated fatty acids (LC ω3-PUFAs) were pooled using a random-effects meta-analysis. A dose-response analysis was conducted with the 2-stage generalized least-squares trend program. RESULTS: Our meta-analysis identified a total of 17 prospective cohort studies including 14986 strokes events in 672711 individuals. Meta-analysis revealed that the higher fish consumption was significantly associated with lower risk of stroke (RR=0.871, 95% CI: 0.779-0.975, p=0.016), especially with ischemic stroke (RR=0.808, 95% CI: 0.696- 0.937, p=0.005). Meantime, the combined RR of total stroke was 0.859 (95% CI: 0.769-0.959, p=0.007) for the highest versus lowest intake of LC ω3-PUFAs, and stratification analysis showed that higher LC ω3-PUFAs intake was associated with reduced stroke risk in women (RR=0.793, 95% CI: 0.706-0.891, p=0.000) but not in men. In addition, the dose-response analysis showed fish consumption with 1000g per month and LC ω3-PUFAs intake with 0.5g per month was associated with 17.3% (RR=0.927, 95% CI: 0.83-0.98) and 14% (RR=0.86, 95% CI: 0.78-0.95) lower risk of stroke, respectively. CONCLUSIONS: Both fish consumption and LC ω3-PUFAs intake were negatively associated with the risk of stroke, especially in women, which suggest that increased intake of fishery products and LC ω3-PUFAs may benefit primary prevention of stroke.

Fingerprint and multi-index content determination of ethyl acetate extract of Sedum emarginatum Migo.

Sedum emarginatum Migo (Aoyejingtian) is a perennial succulent herb of the sedum genus in the family Crassulaceae, which has the fountion of treating furuncle, swelling and haematemesis, hematochezia, menorrhagia and hepatitis. Preliminary studies of our research group had showed that the ethyl acetate extract of Sedum emarginatum Migo could inhibit the proliferation of liver cancer HepG2 cells. The establishment of a reasonable and feasible quality evaluation method for the effective parts of Sedum emarginatum Migo can provide a scientific basis for the further development and utilization of Sedum emarginatum Migo. In this study, a multi-wavelength conversion method was used to establish high-performance liquid chromatography (HPLC) fingerprints of the ethyl acetate extract of Sedum emarginatum Migo, and the method was also used to simultaneously determine the gallic acid, protocatechuic acid, caffeic acid, and ferulic acid, isoquercitrin and luteolin in the ethyl acetate extract of Sedum emarginatum Migo. The similarity of the fingerprints of the ethyl acetate extract of Sedum emarginatum Migo from different origins and the content of 6 components were compared. The established method was simple, accurate, table and reliable, which could provide a fast, accurate and reliable method for comprehensive evaluation of the quality of Sedum emarginatum Migo.

[Association between serum uric acid and subclinical cardiac damage in children with primary hypertension].

OBJECTIVE: To evaluate the condition of subclinical cardiac damage in children with primary hypertension and the association between serum uric acid and subclinical cardiac damage. METHODS: A retrospective analysis was performed on the medical data of 55 children who were hospitalized and diagnosed with primary hypertension in the Department of Cardiology, Children's Hospital of Soochow University from January 2015 to June 2020. Forty-five healthy children, matched for age and sex, were enrolled as the control group. The two groups were compared in terms of clinical features, laboratory examination, and parameters for left ventricular structure, systolic function, and diastolic function. The correlation of serum uric acid with the parameters for left ventricular structure, systolic function, and diastolic function in children with primary hypertension was analyzed. RESULTS: Compared with the control group, the hypertension group had significantly higher left ventricular mass (LVM), left ventricular mass index (LVMI), and relative wall thickness (RWT) (P < 0.05). Among the children with primary hypertension, 20 (36%) had left ventricular hypertrophy. The hypertension group had significantly larger left atrial diameter and aortic root diameter than the control group (P < 0.05). The hypertension group had a significantly higher ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity than the control group (P < 0.05). The correlation analysis showed that in children with primary hypertension, serum uric acid was positively correlated with LVM (r=0.534, P < 0.01), left atrial diameter (r=0.459, P < 0.01), and aortic root diameter (r=0.361, P=0.010). After adjustment for blood pressure, serum uric acid was still positively correlated with the above parameters (P < 0.05). CONCLUSIONS: Children with primary hypertension may have subclinical cardiac damage such as left ventricular hypertrophy, left ventricular diastolic dysfunction, left atrial enlargement, and proximal aortic dilation. Elevated serum uric acid is significantly associated with cardiac damage in children with primary hypertension.

Kawasaki disease OX40-OX40L axis acts as an upstream regulator of NFAT signaling pathway.

BACKGROUND: We investigated a costimulatory molecule OX40-OX40L acting as an upstream regulator to regulate the nuclear factor of activated T cell (NFAT) in the acute phase of Kawasaki disease (KD). METHODS: One hundred and one samples were collected and divided into six groups: coronary artery lesion (KD-CAL) before intravenous immunoglobulin (IVIG), KD-CAL after IVIG, KD without CAL (KD-nCAL) before IVIG, KD-nCAL after IVIG, fever of unknown (Fou), and Healthy. In vitro OX40-stimulating and OX40L-inhibiting tests were conducted in Healthy and KD groups, respectively. Both the messenger RNA (mRNA) and protein expression levels of OX40, OX40L, NFAT1, and NFAT2 were investigated using quantitative reverse transcription PCR and immunoblotting assay, respectively. RESULTS: The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased in KD-CAL and KD-nCAL groups before IVIG compared with Fou and Healthy groups and decreased after IVIG. A positive correlation was found between them in KD. In vitro OX40-stimulating test demonstrated the significantly increased mRNA and protein expression levels of NFAT1 and NFAT2 in the peripheral blood mononuclear cells of the Healthy group. Meanwhile, OX40L-inhibiting test showed significantly decreased expression levels of NFAT1 and NFAT2 in the KD group. CONCLUSION: OX40-OX40L acts as an upstream regulator in the NFAT signaling pathway involved in KD.

Microglial activation mediates chronic mild stress-induced depressive- and anxiety-like behavior in adult rats.

BACKGROUND: Depression is a heterogeneous disorder, with the exact neuronal mechanisms causing the disease yet to be discovered. Recent work suggests it is accompanied by neuro-inflammation, characterized, in particular, by microglial activation. However, microglial activation and its involvement in neuro-inflammation and stress-related depressive disorders are far from understood. METHODS: We utilized multiple detection methods to detect the neuro-inflammation in the hippocampus of rats after exposure to chronic mild stress (CMS). Male Sprague Dawley (SD) rats were subjected to chronic mild stressors for 12 weeks. Microglial activation and hippocampal neuro-inflammation were detected by using a combinatory approach of in vivo [18F] DPA-714 positron emission computed tomography (PET) imaging, ionized calcium-binding adapter molecule 1 and translocator protein (TSPO) immunohistochemistry, and detection of NOD-like receptor protein 3 (NLRP3) inflammasome and some inflammatory mediators. Then, the rats were treated with minocycline during the last 4 weeks to observe its effect on hippocampal neuro-inflammation and depressive-like behavior induced by chronic mild stress. RESULTS: The results show that 12 weeks of chronic mild stress induced remarkable depressive- and anxiety-like behavior, simultaneously causing hippocampal microglial activation detected by PET, immunofluorescence staining, and western blotting. Likewise, activation of NLRP3 inflammasome and upregulation of inflammatory mediators, such as interleukin-1ß (IL-1ß), IL-6, and IL-18, were also observed in the hippocampus after exposure to chronic stress. Interestingly, the anti-inflammatory mediators, such as IL-4 and IL-10, were also increased in the hippocampus following chronic mild stress, which may hint that chronic stress activates different types of microglia, which produce pro-inflammatory cytokines or anti-inflammatory cytokines. Furthermore, chronic minocycline treatment alleviated the depressive-like behavior induced by chronic stress and significantly inhibited microglial activation. Similarly, the activation of NLRP3 inflammasome and the increase of inflammatory mediators were not exhibited or significantly less marked in the minocycline treatment group. CONCLUSION: These results together indicate that microglial activation mediates the chronic mild stress-induced depressive- and anxiety-like behavior and hippocampal neuro-inflammation.

Iris colour in relation to myopia among Chinese school-aged children.

PURPOSE: Understanding the association of iris colour and myopia may provide further insights into the role of the wavelength of lights in the pathophysiology of myopia. We aim to assess the association of iris colour and myopia in a school-based sample of Chinese students. METHODS: Two thousand three hundred and forty-six Year 7 students from 10 middle schools (93.5% response rate) aged 13-14 years in Mojiang, a small county located in Southwestern China, participated in the study. We obtained standardised slit lamp photographs and developed a grading system assessing iris colour (higher grade denoting a darker iris). Refractive error was measured after cycloplegia using an autorefractor by optometrists or trained technicians. An IOLMaster (www.zeiss.com) was used to measure ocular biometric parameters including axial length (AL). RESULTS: Of all the study participants, 693 (29.5%) were affected by myopia with the prevalence estimates being higher in girls (36.8%; 95% confidence interval [CI]: 34.0, 39.6) than in boys (22.8%; 95% CI: 20.4, 25.1) (p < 0.001). After adjusting for gender, height, parental history of myopia, time spent on computer, time spent watching TV, time spent outdoors, and time spent reading and writing, participants with a darker iris colour tended to have a higher prevalence of myopia, a more myopic refraction and a longer AL. Dose-response relationships were observed in all regression models (p for trend <0.05). CONCLUSIONS: Darker iris colour was associated with more myopic refractive errors and longer ALs among Chinese school-aged children and this association was independent of other known myopia-related risk factors.

Anti-HIV diarylpyrimidine-quinolone hybrids and their mode of action.

A molecular hybridization approach is a powerful tool in the design of new molecules with improved affinity and efficacy. In this context, a series of diarylpyrimidine-quinolone hybrids were synthesized and evaluated against both wt HIV-1 and mutant viral strains. The most active hybrid 5a displayed an EC50 value of 0.28±0.07µM against HIV-1 IIIB. A couple of enzyme-based assays clearly pinpoint a RT-targeted mechanism of action. Docking studies revealed that these hybrids could be well located in the NNIBP of HIV-1 RT despite the bulky and polar properties of a quinolone 3-carboxylic acid moiety in the molecules.

Synthesis and biological evaluation of DAPY-DPEs hybrids as non-nucleoside inhibitors of HIV-1 reverse transcriptase.

A series of new DAPY-DPEs hybrids, combined the important pharmacophores of DAPYs and DPEs, has been synthesized and biologically evaluated for their anti-HIV activities against wild-type HIV-1 strain IIIB, double RT mutant (K103N+Y181C) strain RES056 and HIV-2 strain ROD in MT-4 cell cultures. Many promising candidates with potent inhibitory activity (wild-type) within the EC50 range from 0.16 to 0.013 µM were obtained. In particular, 3c, 3p, 3r and 3s displayed low nM level EC50 values (35, 13, 50 and 17 nM, respectively) and high selectivity (9342, 25131, 2890 and 11338, respectively), which were much more potent than NVP (EC50=0.31 µM, SI=48), 3TC (EC50=2.24 µM, SI>39), DDI (EC50=23.20 µM, SI>9) and DLV (EC50=0.65 µM, SI>67), and comparable to AZT (EC50=0.0071 µM, SI>13144) and EFV (EC50=0.0062 µM, SI>1014). The HIV-1 reverse transcriptase inhibitory assay confirmed that these DAPY-DPEs hybrids targeted HIV-1 RT. Molecular simulation was performed to investigate the potential binding mode of the newly synthesized compounds. And reasonable explanation for the activity results was discussed with docking method.