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1.
Nanoscale ; 2022 May 17.
Article in English | MEDLINE | ID: mdl-35579287

ABSTRACT

Removal of water from a mixture of water and inorganic solids usually leads to a drastic change in the mechanical properties from liquid-like to brittle solid type. Here, we demonstrate that there is an unusual state, the X state, formed by naturally drying up a dough which is composed of Ni(H2O)2[(Ni(CN)4]·H2O nanosheets and water. This X-state mixture shows mechanical characteristics different from both pure liquids and brittle solids. The deformation curve of the X-state mixture contains three linear parts. However, the deformation is recoverable because the deformation curve can be repeated as long as fracture does not occur. The ice-like water formed among the nanosheets is believed to be an important reason for generating this X-state mixture. The unique properties of the X-state mixture may find applications, such as impact absorbents, which require materials with considerable strength, modulus and toughness.

2.
Int J Infect Dis ; 2022 May 13.
Article in English | MEDLINE | ID: mdl-35577247

ABSTRACT

OBJECTIVES: To track the prevalence trend of latent tuberculosis infection (LTBI) at the global, regional, and country levels. METHODS: Data on the prevalence of LTBI were extracted from the Global Burden of Disease database. The average annual percent change (AAPC) was estimated by Joinpoint Regression and was used to evaluate the epidemic of the disease. RESULTS: Globally, the prevalence rate of LTBI decreased from 30.66% in 1990 to 23.67% in 2019 with an AAPC of -0.9%. The prevalence rate of LTBI varied from 5.02% (Jordan) to 48.35% (Uganda) in 1990 and from 2.51% (Jordan) to 43.75% (Viet Nam) in 2019 at the country level. The prevalence decreased in all the six WHO regions and in the vast majority of countries, with the AAPC ranging from -0.5% in the Western Pacific Region to -2.1% in the European Region, and from -4.3% (Bhutan) to -0.1% (Malaysia, Myanmar, South Africa, Tokelau, and Viet Nam), respectively. Disparities were also observed among different sex and age groups. CONCLUSIONS: The prevalence of LTBI decreased slightly globally in the last three decades, but the decrease is slow and not sufficient to meet the targets of WHO TB elimination. Much more effort and progress should be made in order to reduce the prevalence of LTBI.

3.
Nanomaterials (Basel) ; 12(9)2022 May 07.
Article in English | MEDLINE | ID: mdl-35564301

ABSTRACT

Single-atom non-precious metal oxygen reduction reaction (ORR) catalysts have attracted much attention due to their low cost, high selectivity, and high activity. Herein, we successfully prepared iron single atoms anchored on nitrogen-doped carbon matrix/nanotube hybrid supports (FeSA-NC/CNTs) by the pyrolysis of Fe-doped zeolitic imidazolate frameworks. The nitrogen-doped carbon matrix/carbon nanotube hybrid supports exhibit a specific surface area of 1626.814 m2 g-1, which may facilitate electron transfer and oxygen mass transport within the catalyst and be beneficial to ORR performance. Further electrochemical results revealed that our FeSA-NC/CNTs catalyst exhibited excellent ORR activity (half-wave potential: 0.86 V; kinetic current density: 39.3 mA cm-2 at 0.8 V), superior to that of commercial Pt/C catalyst (half-wave potential: 0.846 V; kinetic current density: 14.4 mA cm-2 at 0.8 V). It also has a great stability, which makes it possible to be a valuable non-noble metal electrode material that may replace the latest commercial Pt/C catalyst in the future.

4.
Chin J Nat Med ; 20(5): 378-386, 2022 May.
Article in English | MEDLINE | ID: mdl-35551772

ABSTRACT

The dry root and rhizome of Panax ginseng C. A. Mey has garnered much interest owing to its medicinal properties against diabetes and cardiovascular diseases. In this study, an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS)-based metabolomics approach was used to illustrate the therapeutic mechanisms of ginseng extract on the serum and urinary metabolic profiles in streptozotocin-induced type 1 diabetes mellitus (T1DM) rats. Pharmacological and renal parameters in response to the administration of ginseng were also evaluated. In total, 16 serum endogenous metabolites and 14 urine endogenous metabolites, including pyruvic acid, indoleacetic acid, and phenylacetylglycine, were identified as potential biomarkers for diabetes. Pathway enrichment and network analysis revealed that the biomarkers modulated by ginseng were primarily involved in phenylalanine and pyruvate metabolism, as well as in arginine biosynthesis. Moreover, the levels of several renal injury-related biomarkers in T1DM rats were significantly restored following treatment with ginseng. The administration of the extract helped maintain tissue structure integrity and ameliorated renal injury. The findings suggest that the regulatory effect of ginseng extract on T1DM involves metabolic management of diabetic rats, which subsequently attenuates T1DM-induced early renal dysfunction.

5.
FASEB J ; 36 Suppl 12022 May.
Article in English | MEDLINE | ID: mdl-35553310

ABSTRACT

BACKGROUND: NHERF1 (Na+ -hydrogen exchanger regulatory factor isoform 1), recognized as a scaffold protein that regulates proximal tubule phosphate transport, also has a role in regulation of cell metabolism and survival. Our laboratory previously demonstrated more severe cisplatin-induced acute kidney injury (AKI) in the global NHERF1 knock out (KO) mouse compared to the cisplatin-treated wild type (WT) mouse. In the present study, we tested the hypothesis that kidney injury results in decreased NHERF1 expression by examining NHERF1 expression in two models of AKI (cisplatin and bilateral renal ischemia-reperfusion) and two models of chronic kidney disease or CKD (adenine diet and Col4a3-/- ) by immunofluorescent microscopy and western blot analysis. METHODS: Cisplatin-induced AKI:Two-month-old male and female C57BL/6J WT mice received a single intraperitoneal injection of saline (vehicle) or 20 mg/kg cisplatin. Vehicle- and cisplatin-treated mice were euthanized after 72 hours. Bilateral renal ischemia-reperfusion injury AKI: Two-month-old male and female C57Bl/6J WT mice underwent bilateral renal artery clamp for 30 minutes followed by release. Sham and IRI surgery treated mice were euthanized at 2, 4, and 14 days post-surgery. Adenine-induced CKD: Two-month-old male and female C57Bl/6J WT mice received either regular or adenine-supplemented chow for 20 weeks followed by euthanasia. Col4a3-/- CKD: Two-month-old male and female C57Bl/6J heterozygous and homozygous KO mice for the collagenase type IV alpha 3 chain were followed for up to 7 months followed by euthanasia. In all four mouse models, the kidneys were removed, de-capsulated, immersed in 3.7% formaldehyde in phosphate-buffered saline for 24 hours, then transferred to 70% ethanol for paraffin embedding and immunofluorescent microscopy. Western blots of kidney lysates from each kidney injury model were electrophoresed in 4-12% Bis-Tris gradient gels and immunoblotted for NHERF1. RESULTS: Immunofluorescent microscopy revealed increased staining for NHERF1 at or near the apical membrane of proximal tubule epithelial cells in all four mouse injury models. For the IRI model, longitudinal immunohistochemistry demonstrated a progressive increase in the apical NHERF1 signal from baseline through day 4 post-surgery followed by a decrease to baseline levels by day 14. Western blot analysis of lysates from all four kidney injury models showed no change in total expression of NHERF1. CONCLUSIONS: We conclude that kidney injury results in translocation of NHERF1 to the apical membrane. These findings suggest that NHERF1 plays a significant role in the response to kidney injury, though at this time, neither the mechanism for translocation nor the specific role of NHERF1 in the response to injury is clear.

6.
Front Plant Sci ; 13: 852750, 2022.
Article in English | MEDLINE | ID: mdl-35557713

ABSTRACT

Bacterial soft rot is one of the most destructive diseases of taro (Colocasia esculenta) worldwide. In recent years, frequent outbreaks of soft rot disease have seriously affected taro production and became a major constraint to the development of taro planting in China. However, little is known about the causal agents of this disease, and the only reported pathogens are two Dickeya species and P. carotovorum. In this study, we report taro soft rot caused by two novel Pectobacterium strains, LJ1 and LJ2, isolated from taro corms in Ruyuan County, Shaoguan City, Guangdong Province, China. We showed that LJ1 and LJ2 fulfill Koch's postulates for taro soft rot. The two pathogens can infect taro both individually and simultaneously, and neither synergistic nor antagonistic interaction was observed between the two pathogens. Genome sequencing of the two strains indicated that LJ1 represents a novel species of the genus Pectobacterium, for which the name "Pectobacterium colocasium sp. nov." is proposed, while LJ2 belongs to Pectobacterium aroidearum. Pan-genome analysis revealed multiple pathogenicity-related differences between LJ1, LJ2, and other Pectobacterium species, including unique virulence factors, variation in the copy number and organization of Type III, IV, and VI secretion systems, and differential production of plant cell wall degrading enzymes. This study identifies two new soft rot Pectobacteriaceae (SRP) pathogens causing taro soft rot in China, reports a new case of co-infection of plant pathogens, and provides valuable resources for further investigation of the pathogenic mechanisms of SRP.

7.
Front Aging Neurosci ; 14: 869708, 2022.
Article in English | MEDLINE | ID: mdl-35557835

ABSTRACT

Background: Elderlies and tinnitus patients often find it challenging to process acoustic signals in noisy environments. The sensitivity to temporal fine structure (TFS), the transient storage capacity for TFS, and the ultra-high frequency (UHF) thresholds are all associated with aging-related damage, evidenced by speech-in-noise perception deficits. In the present study, we aimed to investigate the relationships among TFS sensitivity, transient storage capacity, and UHF thresholds in tinnitus patients and normal adults of different ages. Methods: In the present study, 38 tinnitus patients (age ranging from 21 to 65) and 23 non-tinnitus adults (age ranging from 22 to 56) were enrolled, and some of their auditory indicators were examined, including the TFS-adaptive frequency (TFS-AF), break in interaural correlation (BIAC) delay threshold, and UHF thresholds. Results: We found no significant difference in TFS-AF thresholds and BIAC delay thresholds between the tinnitus group and normal group, while their relationships with age were more evident in the tinnitus group. Moreover, these two tests were only significantly correlated in the tinnitus group. UHF thresholds were significantly correlated with TFS-AF thresholds only in the tinnitus group, suggesting that the UHF hearing was positively associated with the TFS sensitivity. Conclusion: These findings indicated that the influencing factors, such as tinnitus and UHF thresholds, should be fully considered when examining age-related hearing decline, because the combination of tinnitus and poor UHF hearing might play a role in affecting hearing ability, such as TFS sensitivity.

8.
RSC Adv ; 8(73): 41810-41817, 2018 Dec 12.
Article in English | MEDLINE | ID: mdl-35558782

ABSTRACT

Eleven new polyketones named diaporthsins A-K (1-11) were isolated from the fermentation of Diaporthe sp. JC-J7. The chemical structures of compounds (1-11) were elucidated by spectroscopic methods including HRESIMS, 2DNMR, NMR and chemical methods. Compound 11 features an unusual acyclic polyketone-phenolic polyketone hybrid structure that integrates the characteristics of different fungal metabolites (cytosporone and multiplolide). Compound 3 was the only C12-polyketone obtained in this research. These new polyketones showed inhibitory activity on triglycerides (TG) in steatosis hepatocyte L-02 cells. Among them, compound 5 and (4E)-6,7,9-trihydroxydec-4-enoic acid displayed inhibitory activities on TG in steatotic L-02 cells with inhibition ratios of 26% and 21% at concentration of 5 µg mL-1; also, inhibition ratios of 8-O-acetylmultiplolide A and phomopsisporone A at concentration of 5 µg mL-1 were calculated to be about 24% and 16%, respectively, which were equivalent to the antihyperlipidemic activity of lovastatin. The preliminary structure-activity relationship indicated that acetyl at C-8 can increase the antihyperlipidemic activity of multiplolide A and the glycol ester and hydroxyl at C-6 can also increase the corresponding activity of diaporthsin B.

9.
RSC Adv ; 9(61): 35345-35355, 2019 Oct 31.
Article in English | MEDLINE | ID: mdl-35528086

ABSTRACT

With Span and polyethylene glycol (PEG) as the membrane material, the as-prepared folate-carbon nanotube-paclitaxel (FA-CNT-PTX) complex was added to the reaction system under sound vibration cavitation and Span-PEG with FA-CNT-PTX microbubbles was obtained. The maximum tolerating dose of the obtained composite microbubbles on Kunming mice was determined by acute toxicity test. Utilizing the breast cancer tumor model in the nude mice to assess the anti-tumor activity in vivo, the inhibition effect of the composite microbubbles on tumor growth was analyzed by recording the weight and tumor volume of the nude mice. HE staining observations, the immunohistochemistry method, and TUNEL were, respectively, used to examine the inhibition effect of the composite microbubbles on breast cancer tumors in the nude mice. The ultrasound imaging effects and the changes in the peak intensities of the composite microbubbles were inspected using a Doppler color ultrasound imaging system. The experimental results showed that the maximum tolerated dose of the composite microbubbles was 3500 mg kg-1, indicating that the composite microbubbles had low toxicity and good biocompatibility. The composite microbubbles could reach the breast cancer tumor via a targeting factor, and then hindered the tumor growth by inhibiting the proliferation of tumor cells and inducing apoptosis of the tumor cells. The composite microbubbles contributed toward enhancing the ultrasound signal and improved the resolution of the ultrasound images and extended the imaging time. Also, the addition of CNTs in the composite microbubbles could enhance the ultrasound contrast. Simultaneously, the peak intensity at the tumor was significantly reduced after the treatment.

10.
Surg Endosc ; 2022 May 09.
Article in English | MEDLINE | ID: mdl-35534731

ABSTRACT

BACKGROUND: Robotic liver resection (RLR) has increasingly been accepted as it has overcome some of the limitations of open liver resection (OLR), while the outcomes following RLR in elderly patients with hepatocellular carcinoma (HCC) are still uncertain. This study aimed to evaluate the short and long-term outcomes of RLR vs. OLR in elderly HCC patients. METHODS: Perioperative data of elderly patients (≥ 65 years) with HCC who underwent RLR or OLR between January 2010 and December 2020 were retrospectively analyzed. A 1:2 propensity score-matched (PSM) analysis was performed to minimize the differences between RLR and OLR groups. Univariable and multivariable Cox regression analyses were used to identify independent prognosis factors for overall survival (OS) and recurrence-free survival (RFS) of these patients. RESULTS: Of the 427 elderly HCC patients included in this study, 113 underwent RLR and 314 underwent OLR. After the 1:2 PSM, there were 100 and 178 patients in the RLR and the OLR groups, respectively. The RLR group had a less estimated blood loss (EBL), a shorter postoperative length of stay (LOS), and a lower complications rate (all P < 0.05), compared with the OLR group before and after PSM. Univariable and multivariable analyses showed that advanced age and surgical approaches were not independent risk factors for long-term prognosis. The two groups of elderly patients who were performed RLR or OLR had similar OS (median OS 52.8 vs. 57.6 months) and RFS (median RFS 20.4 vs. 24.6 months) rates after PSM. CONCLUSIONS: RLR was comparable to OLR in feasibility and safety. For elderly patients with HCC, RLR resulted in similar oncologic and survival outcomes as OLR.

11.
Surg Endosc ; 2022 May 09.
Article in English | MEDLINE | ID: mdl-35534733

ABSTRACT

BACKGROUND: Pancreatoduodenectomy is the only potentially curative treatment for distal cholangiocarcinoma (DCC). In this study, we sought to compare the perioperative and oncological outcomes of robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD) based on a multicenter propensity score-matched study. METHODS: Consecutive patients with DCC who underwent RPD or OPD from five centers in China between January 2014 and June 2019 were included. A 1:1 propensity score matching (PSM) was performed. Univariable and multivariable Cox regression analyses were used to identify independent prognosis factors for overall survival (OS) and recurrence-free survival (RFS) of these patients. RESULTS: A total of 217 patients and 228 patients underwent RPD and OPD, respectively. After PSM, 180 patients in each group were enrolled. There were no significant differences in operative time, lymph node harvest, intraoperative transfusion, vascular resection, R0 resection, postoperative major morbidity, reoperation, 90-day mortality, and long-term survival between the two groups before and after PSM. Whereas, compared with the OPD group, the RPD group had significantly lower estimated blood loss (150.0 ml vs. 250.0 ml; P < 0.001), and a shorter postoperative length of stay (LOS) (12.0 days vs. 15.0 days; P < 0.001). Multivariable analysis showed carbohydrate antigen 19-9 (CA19-9), R0 resection, N stage, perineural invasion, and tumor differentiation significantly associated with OS and RFS of these patients. CONCLUSIONS: RPD was comparable to OPD in feasibility and safety. For patients with DCC, RPD resulted in similar oncologic and survival outcomes as OPD.

12.
RSC Adv ; 10(63): 38592-38600, 2020 Oct 15.
Article in English | MEDLINE | ID: mdl-35517545

ABSTRACT

By attaching ferroferric oxide (Fe3O4) to drug-carrying carbon nanotubes (CNTs), we generated a new Span-PEG composite with Fe3O4-CNT multifunctional microbubbles for inflammation and thrombus niduses. The Fe3O4-CNT magnetic targeting complex was prepared by in situ synthesis, and then acetylsalicylic acid (ASA) and gentamicin (GM) were loaded onto the Fe3O4-CNT complex by physical methods to produce Fe3O4-CNT-ASA and Fe3O4-CNT-GM complexes, respectively. Span-PEG-composited Fe3O4-CNT-ASA or Fe3O4-CNT-GM microbubbles were synthesized with Span and PEG as the membrane materials by the acoustic cavitation method. The obtained composite microbubbles were smooth, hollow spheres with an average particle size of 425 nm. The ASA and GM loading rates in Span-PEG-composited Fe3O4-CNT-ASA and Fe3O4-CNT-GM microbubbles were 1.12% and 19.05%, respectively. Span-PEG-composited Fe3O4-CNT-ASA microbubbles inhibited thrombosis and demonstrated an anticoagulation effect in vitro. Additionally, Span-PEG-composited Fe3O4-CNT-ASA microbubbles showed significantly enhanced ultrasound imaging of rabbit abdominal aorta and extended the signal time under the action of an external magnetic field. Thus, Span-PEG-composited Fe3O4-CNT-GM microbubbles inhibited Escherichia coli and Staphylococcus aureus, enhanced the ultrasound imaging of rabbit abdominal uterus and had better stability and fluidity.

13.
Brief Bioinform ; 2022 Apr 29.
Article in English | MEDLINE | ID: mdl-35488276

ABSTRACT

The three-dimensional organization of chromatin plays a critical role in gene regulation. Recently developed technologies, such as HiChIP and proximity ligation-assisted ChIP-Seq (PLAC-seq) (hereafter referred to as HP for brevity), can measure chromosome spatial organization by interrogating chromatin interactions mediated by a protein of interest. While offering cost-efficiency over genome-wide unbiased high-throughput chromosome conformation capture (Hi-C) data, HP data remain sparse at kilobase (Kb) resolution with the current sequencing depth in the order of 108 reads per sample. Deep learning models, including HiCPlus, HiCNN, HiCNN2, DeepHiC and Variationally Encoded Hi-C Loss Enhancer (VEHiCLE), have been developed to enhance the sequencing depth of Hi-C data, but their performance on HP data has not been benchmarked. Here, we performed a comprehensive evaluation of HP data sequencing depth enhancement using models developed for Hi-C data. Specifically, we analyzed various HP data, including Smc1a HiChIP data of the human lymphoblastoid cell line GM12878, H3K4me3 PLAC-seq data of four human neural cell types as well as of mouse embryonic stem cells (mESC), and mESC CCCTC-binding factor (CTCF) PLAC-seq data. Our evaluations lead to the following three findings: (i) most models developed for Hi-C data achieve reasonable performance when applied to HP data (e.g. with Pearson correlation ranging 0.76-0.95 for pairs of loci within 300 Kb), and the enhanced datasets lead to improved statistical power for detecting long-range chromatin interactions, (ii) models trained on HP data outperform those trained on Hi-C data and (iii) most models are transferable across cell types. Our results provide a general guideline for HP data enhancement using existing methods designed for Hi-C data.

14.
RSC Adv ; 11(41): 25477-25483, 2021 Jul 19.
Article in English | MEDLINE | ID: mdl-35478891

ABSTRACT

In the current study, six ferrocenylseleno-dopamine derivatives with different structural parameters were designed. Among these derivatives, F4b, containing two ferrocene units and a tertiary amine, showed in vitro anticancer activity with IC50 = 2.4 ± 0.4 µM for MGC-803 cells, and its in vivo studies suggested effective antitumor activity in mice bearing an MGC-803 tumor xenograft. Mechanistic study revealed that the cytotoxicity of these ferrocenylseleno-dopamine derivatives is mainly related to the Fenton-like reaction under physiological conditions, and the tertiary amine in F4b can facilitate the H2O2 decomposition to generate toxic ˙OH which induces apoptosis through CDK-2 inactivation.

15.
Fundam Clin Pharmacol ; 2022 Apr 25.
Article in English | MEDLINE | ID: mdl-35470467

ABSTRACT

Stroke is the leading cause of disability and death. When blood flow is restored after prolonged ischemia and hypoxia, it leads to excessive production of reactive oxygen species (ROS), increased local inflammation, and apoptosis, which are the cause of most cerebral ischemia reperfusion injury (CIRI), leading to secondary brain tissue damage. Edaravone dexborneol is a novel neuroprotective agent consisting of edaravone and borneol. Studies have shown that it has synergistic antioxidant and anti-inflammatory effects. However, whether Edaravone dexborneol stimulates the Nrf2/HO-1 pathway to regulate NADPH oxidase 2 (NOX2) remains unclear. In this study, wild-type (WT) mice and Nrf2 knockout (KO) mice were used to investigate the antioxidant, anti-inflammatory, and anti-apoptotic effects of Edaravone dexborneol on CIRI and its mechanism. The cognitive function of mice was evaluated with the Morris water maze (MWM), test and the cell structures of hippocampus were observed by hematoxylin and eosin (H&E) staining. Nrf2, HO-1, and NOX2 proteins and apoptosis-related proteins Bcl-2, Bax, and Caspase 3 were detected by western blotting. Nrf2, HO-1, NOX2, and inflammatory factors TNF-α, IL-1ß, IL-4, and IL-10 were detected by real-time polymerase chain reaction. The results showed that Edaravone dexborneol treatment improved learning and memory performance, neuronal damage, and enhanced antioxidant, inflammation, and apoptosis in CIRI mice. In addition, Edaravone dexborneol induced the activation Nrf2/HO-1 signaling pathway activation while inhibiting NOX2 expression. Overall, these results indicate that Edaravone dexborneol ameliorates CIRI-induced memory impairments by activating Nrf2/HO-1 signaling pathway and inhibiting NOX2.

16.
Environ Res ; 212(Pt B): 113345, 2022 Apr 22.
Article in English | MEDLINE | ID: mdl-35469855

ABSTRACT

Polybrominated diphenyl ethers (PBDEs) are widespread and persistent environmental contaminants, but their association with nodular goiter (NG) remains unknown. The present case-control study of 179 NG cases and 358 matched normal controls aimed to investigate the association between PBDEs and risk of NG. The plasma concentrations of 8 PBDEs congeners (BDE-28, -47, -99, -100, -153, -154, -183, and -209) were determined by gas chromatograph-mass spectrometer. Conditional logistic regression model was used to evaluate the odds ratio (OR) and 95% confidence interval (CI) for the association between each PBDEs congener and NG. Bayesian kernel machine regression (BKMR) was used to evaluate the association between overall levels of 8 PBDEs mixture and NG. The results of logistic model suggested that increased risk of NG was associated with elevated concentrations of all PBDEs congeners, except for BDE-209. In BKMR model, the risk of NG increased with the increase in overall exposure level of 8 PBDEs mixture. Compared to when all PBDEs mixture were at their median value, the risk of exposure-response function for NG increased by 0.34 units when all PBDEs were at their 75th percentile. In women, the results showed similar trends after additional adjustment for age at menarche and menopausal status. These findings provide novel epidemiological evidence for the prevention of NG. However, larger prospective studies are required to address the associations between PBDEs exposure and NG risk.

17.
Signal Transduct Target Ther ; 7(1): 137, 2022 Apr 25.
Article in English | MEDLINE | ID: mdl-35468896

ABSTRACT

Whether and how innate antiviral response is regulated by humoral metabolism remains enigmatic. We show that viral infection induces progesterone via the hypothalamic-pituitary-adrenal axis in mice. Progesterone induces downstream antiviral genes and promotes innate antiviral response in cells and mice, whereas knockout of the progesterone receptor PGR has opposite effects. Mechanistically, stimulation of PGR by progesterone activates the tyrosine kinase SRC, which phosphorylates the transcriptional factor IRF3 at Y107, leading to its activation and induction of antiviral genes. SARS-CoV-2-infected patients have increased progesterone levels, and which are co-related with decreased severity of COVID-19. Our findings reveal how progesterone modulates host innate antiviral response, and point to progesterone as a potential immunomodulatory reagent for infectious and inflammatory diseases.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antiviral Agents , COVID-19/genetics , Humans , Hypothalamo-Hypophyseal System , Immunity, Innate/genetics , Mice , Pituitary-Adrenal System , Progesterone/pharmacology
18.
Genes (Basel) ; 13(4)2022 03 25.
Article in English | MEDLINE | ID: mdl-35456393

ABSTRACT

The human genome has a complex and dynamic three-dimensional (3D) organization, which plays a critical role for gene regulation and genome function. The importance of 3D genome organization in brain development and function has been well characterized in a region- and cell-type-specific fashion. Recent technological advances in chromosome conformation capture (3C)-based techniques, imaging approaches, and ligation-free methods, along with computational methods to analyze the data generated, have revealed 3D genome features at different scales in the brain that contribute to our understanding of genetic mechanisms underlying neuropsychiatric diseases and other brain-related traits. In this review, we discuss how these advances aid in the genetic dissection of brain-related traits.


Subject(s)
Chromatin , Chromosomes , Brain , Gene Expression Regulation , Genome, Human , Humans
19.
J Pers Med ; 12(4)2022 Apr 10.
Article in English | MEDLINE | ID: mdl-35455724

ABSTRACT

The objective of this study was to identify biomarkers that predict a future need for anti-VEGF therapy in diabetic retinopathy (DR). Eyes with DR that underwent ultra-widefield angiography (UWFA) and had at least a 1 year follow-up were grouped based on future anti-VEGF treatment requirements: (1) not requiring treatment, (2) immediate treatment (within 3 months of UWFA), and (3) delayed treatment (after 3 months of UWFA). Quantitative UWFA features and clinical factors were evaluated. Random forest models were built to differentiate eyes requiring immediate and delayed treatment from the eyes not requiring treatment. A total of 173 eyes were included. The mean follow-up was 22 (range: 11-43) months. The macular leakage index, panretinal leakage index, presence of DME, and visual acuity were significantly different in eyes requiring immediate (n = 38) and delayed (n = 34) treatment compared to eyes not requiring treatment (n = 101). Random forest model differentiating eyes requiring immediate treatment from eyes not requiring treatment demonstrated an AUC of 0.91 ± 0.07. Quantitative angiographic features have potential as important predictive biomarkers of a future need for anti-VEGF therapy in DR and may serve to guide the frequency of a follow-up.

20.
Micromachines (Basel) ; 13(4)2022 Mar 30.
Article in English | MEDLINE | ID: mdl-35457848

ABSTRACT

We demonstrate a hybrid laser microfabrication approach, which combines the technical merits of ultrafast laser-assisted chemical etching and carbon dioxide laser-induced in situ melting for centimeter-scale and bonding-free fabrication of 3D complex hollow microstructures in fused silica glass. With the developed approach, large-scale fused silica microfluidic chips with integrated 3D cascaded micromixing units can be reliably manufactured. High-performance on-chip mixing and continuous-flow photochemical synthesis under UV irradiation at ~280 nm were demonstrated using the manufactured chip, indicating a powerful capability for versatile fabrication of highly transparent all-glass microfluidic reactors for on-chip photochemical synthesis.

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