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1.
Front Nutr ; 9: 871697, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548570

RESUMO

Objective: Abdominal adipose is closely related to many endocrine and metabolic diseases. The aim of this study was to analyze the distribution of abdominal adipose tissue in a healthy population in northern China determined by abdominal computed tomography (CT). Methods: Data for this study were obtained from a multicenter, retrospective, cross-sectional study that collected abdominal CT scans of 1787 healthy individuals from 4 representative cities in northern China. Areas of visceral adipose tissue (VATA) and subcutaneous adipose tissue (SATA) were obtained by measuring CT images at the level of the 3rd lumbar vertebra. Visceral adipose tissue index (VATI) and subcutaneous adipose index (SATI) were obtained by normalizing the square of height to analyze the distribution of the above indexes and visceral obesity among different body mass index (BMI), gender and age. Results: The mean age of this healthy population was 45.3 ± 15.2 years and the mean BMI was 23.5 ± 3.2 kg/m2, with 902 men and 885 women. Compared with women, men had a significantly higher median VATA (120.9 vs. 67.2 cm2), VATI (39.1 vs. 25.6 cm2/m2) and a significantly higher percentage of visceral adiposity (VATA ≥ 100 cm2) (60.8 vs. 30.4%), while women had significantly higher SATA (116.9 vs. 146.7 cm2) and SATI (38.8 vs. 55.8 cm2/m2) than men. Whether men or women, VATI was positively correlated with age. Interestingly, SATI was weakly positively correlated with age in women, while SATI was weakly negatively correlated with age in men. In persons with a normal BMI, the proportion of visceral adiposity increases with age, whereas in men with a normal BMI, the proportion of visceral adiposity decreases after the age of 60 years but remains >50%. Conclusions: The distribution of abdominal visceral and subcutaneous adipose tissue parameters measured by CT differed among gender, age, and BMI. Even men and women with normal BMI have a high proportion of visceral obesity.

2.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35552026

RESUMO

With-no-lysine kinase 4 (WNK4) activates the NaCl cotransporter (NCC) which is the main pathway for sodium reabsorption in the distal convoluted tubule (DCT) of the kidney. The cullin-RING ubiquitin ligase cullin 3 (CUL3) regulates WNK4 abundance via interaction through the substrate adaptor KLHL3. The monogenic disease familial hyperkalemic hypertension (FHHt) is caused by mutations in this pathway. Mutations in KLHL3 and WNK4 mainly disrupt formation of this complex, whereas, the CUL3 mutations impair binding to the COP9 signalosome (CSN), a deneddylase and upstream regulator of cullin-RING ligases. Since FHHt is mostly a disease that affects the DCT, we proposed that DCT-specific knockdown of the main CSN subunit, JAB1, would phenocopy FHHt. We deleted Jab1 in the DCT using the tamoxifen inducible NCC-Cre-ERT2 mouse model (DCT-Jab1-/- ). After five days of tamoxifen administration, proximal tubule, thick ascending limb, DCT, and connecting tubule/collecting duct segments were individually dissected and isolated to analyze protein abundance of each specific segment via Western blot. JAB1 and CUL3 protein abundance were substantially reduced in the DCT of DCT-Jab1-/- mice, whereas, WNK4 and phosphorylated NCC (pNCC) abundance were markedly elevated. Western blot analysis of cortical kidney tissue showed lower KLHL3 abundance and significantly higher abundance of phosphorylated SPAK (pSPAK), the intermediary kinase between WNK4 and NCC. Immunofluorescent staining of WNK4 and pSPAK showed increased expression and puncta formation in DCT1 and DCT2 tubules of DCT-Jab1-/- mice. This was not observed in other tubule segments that express WNK4 or pSPAK, such as the thick ascending limb and connecting tubule/collecting duct. Although there was obvious activation of the WNK4-SPAK-NCC pathway DCT-Jab1-/- mice, plasma analysis showed no significant differences in potassium, chloride or TCO2. However, challenging the DCT-Jab1-/- mice with a high potassium diet for seven days exaggerated the differences in pSPAK and pNCC protein abundance and led to a significant increase in plasma potassium. The results indicate that DCT-specific disruption of JAB1 recapitulates many aspects of FHHt, including decreased KLHL3 and CUL3 abundance which leads to activation of the WNK4-NCC pathway and a tendency toward hyperkalemia. These results implicate defective CSN binding as a key component of CUL3-mediated familial hyperkalemic hypertension.

3.
Polymers (Basel) ; 14(9)2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35567050

RESUMO

The growing popularity of quasi-solid-state supercapacitors inevitably leads to the unrestricted consumption of commonly used petroleum-derived polymer electrolytes, causing excessive carbon emissions and resulting in global warming. Also, the porosity and liquid electrolyte uptake of existing polymer membranes are insufficient for well-performed supercapacitors under high current and long cycles. To address these issues, poly(lactic acid) (PLA), a widely applied polymers in biodegradable plastics is employed to fabricate a renewable biocomposite membrane with tunable pores with the help of non-solvent phase inversion method, and a small amount of poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) is introduced as a modifier to interconnect with PLA skeleton for stabilizing the porous structure and optimizing the aperture of the membrane. Owing to easy film-forming and tunable non-solvent ratio, the porous membrane possesses high porosity (ca. 71%), liquid electrolyte uptake (366%), and preferable flexibility endowing the GPE with satisfactory electrochemical stability in coin and flexible supercapacitors after long cycles. This work effectively relieves the environmental stress resulted from undegradable polymers and reveals the promising potential and prospects of the environmentally friendly membrane in the application of wearable devices.

4.
Environ Microbiome ; 17(1): 26, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35570296

RESUMO

BACKGROUND: Metal(loid)s can promote the spread and enrichment of antibiotic resistance genes (ARGs) in the environment through a co-selection effect. However, it remains unclear whether exposure of microorganisms to varying concentrations of selenium (Se), an essential but potentially deleterious metal(loid) to living organisms, can influence the migration and distribution of ARGs in forest soils. RESULTS: Precisely 235 ARGs conferring resistance to seven classes of antibiotics were detected along a Se gradient (0.06-20.65 mg kg-1) across 24 forest soils. (flor)/(chlor)/(am)phenicol resistance genes were the most abundant in all samples. The total abundance of ARGs first increased and then decreased with an elevated available Se content threshold of 0.034 mg kg-1 (P = 2E-05). A structural equation model revealed that the dominant mechanism through which Se indirectly influences the vertical migration of ARGs is by regulating the abundance of the bacterial community. In addition, the methylation of Se (mediated by tehB) and the repairing of DNA damages (mediated by ruvB and recG) were the dominant mechanisms involved in Se resistance in the forest soils. The co-occurrence network analysis revealed a significant correlated cluster between Se-resistance genes, MGEs and ARGs, suggesting the co-transfer potential. Lelliottia amnigena YTB01 isolated from the soil was able to tolerate 50 µg mL-1 ampicillin and 1000 mg kg-1 sodium selenite, and harbored both Se resistant genes and ARGs in the genome. CONCLUSIONS: Our study demonstrated that the spread and enrichment of ARGs are enhanced under moderate Se pressure but inhibited under severe Se pressure in the forest soil (threshold at 0.034 mg kg-1 available Se content). The data generated in this pilot study points to the potential health risk associated with Se contamination and its associated influence on ARGs distribution in soil.

5.
J Thorac Dis ; 14(4): 1020-1030, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35572879

RESUMO

Background: Lung transplantation is a treatment for end-stage lung disease. The optimal transplant strategy for patients with end-stage lung disease complicated by pulmonary hypertension (PH) is controversial. The aim of this study is to review this experience and analyze the outcomes of lung transplantation for PH. Methods: This retrospective study collected data on patients with PH undergoing lung transplantation between March 2016 and December 2019 at a single center in China. The perioperative features and short- and medium-term outcomes between single-lung transplantation (SLT) and double-lung transplantation (DLT) were compared. Kaplan-Meier methods were used to analyze overall survival across a variety of transplantation procedures, age, mean pulmonary artery pressure (mPAP), body mass index (BMI), and indications of transplantation. Results: A total of 63 patients with PH were finally included in the analysis. The mean age, mean BMI, and mPAP were 56.37 years, 19.56 kg/m2, and 35.4 mmHg respectively. The overall 1-, 2-, and 3-year survival was 70%, 63%, and 60%, respectively. Five (7.94%) patients died within 30 days after surgery and nine patients (14.3%) died from infection during the followed-up period. There were no significant differences in the short- and medium-term survival outcomes of SLT and DLT, but postoperative pulmonary function was better in DLT. Patients older than 60 years of age had worse survival (P=0.01). Conclusions: The short- and medium-term survival outcomes between SLT and DLT are similar in selected patients with PH. DLT provides better pulmonary function. Patients older than 60 years are associated with worse survival.

6.
J Thorac Dis ; 14(4): 1099-1105, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35572903

RESUMO

Background: Aggressive management of heart and lung transplant (HLTx) requires a team of specialists with dedicated expert to improve long-term outcomes. This study aimed to summarize practical experiences of anesthetic management in HLTx operations. Methods: This study retrospectively analyzed the anesthesia-related clinical records of 14 cases of HLTx performed from September 2015 to October 2019. Preoperative diagnoses included congenital heart disease with pulmonary arterial hypertension, idiopathic pulmonary arterial hypertension with right heart failure, end-stage cor pulmonale, dilated cardiomyopathy, end-stage heart failure with pulmonary arterial hypertension, congenital heart disease, and lung transplant failure. All recipients received intravenous-inhalation general anesthesia with single-lumen endotracheal intubation, Swan-Ganz catheterization, and transesophageal echocardiography (TEE). Results: All 14 cases of HLTx were completed successfully and the patients were transferred to the intensive care units (ICUs). The postoperative data of the 14 patients were collected from 1 month to 4 years: seven cases survived the first year, four cases died in the short term (within 30 days), and one case died within 24 h. As at the end of November 2019, eight cases were reported dead (the longest survival was 2 years 1 month and 22 days). Four cases used extracorporeal membrane oxygenation (ECMO) for cardiopulmonary support. Conclusions: The success of the HLTx was attributed to the joint efforts of the entire transplantation team. The anesthesiology team was required for experiences in anesthesia for HLTx. The key to anesthesia management was the in-depth participation in preoperative discussions and assessments. Preventing the exacerbation of right heart failure and pulmonary arterial hypertension is critical during the induction of anesthesia. Regulation and support are crucial from the withdrawal of cardiopulmonary bypass (CPB) to within 1 h of the circulation and respiratory functions undertaken independently by the donor heart and lungs.

7.
ACS Omega ; 7(16): 14317-14331, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35573216

RESUMO

The mechanical and creep properties of shale strongly influence artificial hydraulic fracturing, wellbore stability, and the evaluation of reservoir performance in shale gas exploration. This study characterized these mechanical and creep properties at the microscale through nanoindentation tests and evaluated their dependence on the indentation test parameters, specifically, the indentation load and the loading strain rate. The mechanical parameters (the Young's modulus and hardness) of shale were strongly influenced by the magnitude of an indentation load (2-400 mN). Both parameters decreased sharply as the load increased from 2 to 200 mN; they then remained relatively stable at loads of 200-400 mN, suggesting that large indentation loads (200-400 mN) can be used to detect the mechanical responses of bulk shale. In contrast, both parameters increased slightly as the loading strain rate increased from 0.005 to 0.1 s-1. The indentation creep (C IT), related to creep behavior, and the creep strain rate sensitivity (m), related to the creep mechanism of shale, both increased with increasing the indentation load, whereas they decreased with increasing the loading strain rate. This demonstrates that increasing the load or decreasing the loading strain rate can increase creep deformation in shale during nanoindentation creep testing. The values of m varied from 0.040 to 0.124 under different loading conditions, suggesting that dislocation power-law creep may be the main mechanism controlling creep in shale. This study standardizes the testing parameters for the characterization of the mechanical properties of shale by nanoindentation testing and also advances our understanding of the deformation mechanisms of shale at the microscale.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35532068

RESUMO

Cullin-RING ligases (CRLs) are a family of E3 ubiquitin ligases that control cellular processes through regulated degradation. Cullin 3 (CUL3) targets with-no-lysine kinase 4 (WNK4), a kinase that activates the Na-Cl cotransporter (NCC) the main pathway for sodium reabsorption in the distal convoluted tubule (DCT). Mutations in CUL3 lead to familial hyperkalemic hypertension by increasing WNK4 abundance. The COP9 signalosome (CSN) regulates the activity of CRLs by removing the ubiquitin-like protein NEDD8. Genetic deletion of the catalytically active CSN subunit, Jab1, along the nephron in mice (KS-Jab1-/-) led to increased WNK4 abundance, however, NCC abundance was substantially reduced. We hypothesized that the reduction in NCC resulted from cortical injury that led to hypoplasia of segment, which counteracted WNK4 activation of NCC. To test this, we studied KS-Jab1-/- mice at weekly intervals over a period of three weeks. The results showed that NCC abundance was unchanged until three weeks after Jab1 deletion, at which time other DCT-specific proteins were also reduced. The kidney injury markers KIM-1 and NGAL demonstrated kidney injury immediately after Jab1 deletion; however, the damage was initially limited to the medulla. The injury progressed and expanded into the cortex three weeks after Jab1 deletion coinciding with the loss of DCT. The data indicate that nephron-specific disruption of the cullin-RING ligase system results a complex progression of tubule injury that leads to hypoplasia of the DCT.

10.
Transl Lung Cancer Res ; 11(4): 600-606, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35529796

RESUMO

Background: The tracheal tumor is a rare disease with low incidence in the upper airway. Surgical resection and reconstruction are effective and radical treatments for such conditions, but the approaches vary depending on the tumor location. The current report tends to illustrate the clinical practice and advantage of the median sternotomy approach for treating tracheal tumors. Methods: We summarized and demonstrated four cases of tracheal tumors patients who received tracheal resection and reconstruction via median sternotomy approach in our institute. Their clinical data and surgical procedures were also described. The follow-up would be carried on to monitor their prognosis after the operations. Results: Two patients with lower tracheal tumors involving carina received sternotomies, one with the tumor in cervical, thoracic junction, and the other one with thyroid carcinoma involving and extending to the thoracic trachea received half-sternotomies. The surgical procedures were completed smoothly with ideal surgical vision and sufficient operative space. Case 1 and 2 patients underwent tracheal-bronchial end-to-side anastomosis, while the other two patients received end-to-end anastomosis. The thymus and mediastinal tissue were used as the anastomotic buttress. They were discharged no more than 2 weeks after operations. Case 4 was suffered from aspiratory pneumonia and experienced prolonged intensive care unit (ICU) stay and antibiotic use. No other severe complications were recorded in other cases. No anastomotic dehiscence was observed in the postoperative bronchoscopy. Conclusions: Tracheal resection and reconstruction via sternotomy or half-sternotomy is a practical approach for intrathoracic tracheal lesions. It facilitates a satisfying field and anastomosis procedure. The reported cases had ideal surgical outcomes. Although it is convenient in some specific cases, further studies are warranted for its safety and efficacy.

11.
Ann Ital Chir ; 93: 235-240, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35503057

RESUMO

OBJECTIVE: The present study aims to investigate the therapeutic effect and safety of radiofrequency ablation (RFA) of the great saphenous vein in the treatment of varicose veins of the lower extremities. METHODS: Sixty-nine affected limbs of 45 patients were treated with RFA of the great saphenous vein. All patients underwent retrograde puncture of the distal great saphenous vein under the guidance of B-ultrasound. An RFA catheter was introduced 1 cm below the junction of the great saphenous vein and the femoral vein. A tumescent solution was injected around the femoral vein, and the great saphenous vein was ablated section by section from the upper part to the lower part. Twelve months after RFA, color Doppler ultrasound was used to evaluate the closure of great saphenous vein, and changes in the clinical class, etiology, anatomy, pathology (CEAP) classification before and after treatment were compared. The visual analogue score (VAS) was used to evaluate the local pain on the first and third day after operation. The incidence of complications (e.g., phlebitis, thrombosis, infection) was also evaluated. RESULTS: The ablation of the 69 affected limbs in all the 45 patients was successful. Instant B-ultrasound revealed occlusion of the great saphenous vein and the disappearance of blood flow immediately after ablation. There was no reoccurrence in all patients at the 12 month follow-up. The CEAP classification grade after treatment was significantly lower than that before the treatment, and the difference was statistically significant (χ2 = 4.188, P<0.05). The VAS scores on the first and third days after operation were 1.85 ± 0.35 and 0.59 ± 0.21, respectively. Pain was mild, and only two patients required painkillers. No complications were noted, with the exception of five cases of local ecchymosis. CONCLUSION: RFA of the great saphenous vein may represent an effective method for treating varicose veins of the lower extremities. RFA has the advantages of producing less trauma, fewer complications, and a lower incidence of recurrence. KEY WORDS: B-ultrasonography, Pain, Radiofrequency ablation, Varicose veins.


Assuntos
Ablação por Radiofrequência , Varizes , Insuficiência Venosa , Veia Femoral , Humanos , Extremidade Inferior , Dor/etiologia , Ablação por Radiofrequência/efeitos adversos , Veia Safena/diagnóstico por imagem , Veia Safena/cirurgia , Resultado do Tratamento , Varizes/diagnóstico por imagem , Varizes/etiologia , Varizes/cirurgia , Insuficiência Venosa/cirurgia
12.
Sheng Li Xue Bao ; 74(2): 165-176, 2022 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-35503064

RESUMO

This paper was aimed to clarify the effect of high-intensity interval training (HIIT) on depression. Animal running platforms were used to establish HIIT exercise models, depression models were prepared by chronic unpredictable mild stress (CUMS), and depression-related behaviors were detected by behavioral experiments. The results showed that HIIT exercise improved depression-related behavior in CUMS model mice. Western blot and ELISA results showed that in the hippocampus, medial prefrontal cortex (mPFC) and amygdala of the CUMS model mice, glucocorticoid receptor (GR) protein expression was down-regulated, and the content of tumor necrosis factor α (TNF-α) was increased, compared with those in the control group, whereas HIIT exercise could effectively reverse these changes in CUMS model mice. These results suggest that HIIT exercise can exert antidepressant effect, which brings new ideas and means for the clinical treatment of depressive diseases.


Assuntos
Depressão , Estresse Psicológico , Animais , Antidepressivos/farmacologia , Comportamento Animal , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Hipocampo/metabolismo , Camundongos , Estresse Psicológico/tratamento farmacológico
13.
Sci Rep ; 12(1): 7469, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523995

RESUMO

In clinical settings, although Psoriasis Area and Severity Index (PASI) scoring system can provide a quick visual assessment of the severity of psoriasis vulgaris, there is still a strong demand for higher efficiency and accuracy in quantifying the inflammation status of psoriatic lesions. Currently, there are already commercial systems, such as the Courage + Khazaka Corneometer and Mexameter that measure skin capacitance and optical reflectance, for conveniently quantifying the status of skin barrier function and erythema of skin. Despite numerous comparisons of the Courage + Khazaka system with the PASI scoring system, they are rarely compared on parity with diffuse reflectance spectroscopy (DRS) based systems. In this study, we employed a custom-built DRS system shown to be able to determine the skin water-protein binding status and the hemoglobin concentration, and we performed cross-validation of the DRS measurement results with the readings derived from the Corneometer and Mexameter as well as a portion of the PASI scores. Our results revealed that the erythema readings from the Mexameter were a good representation of skin oxygenated hemoglobin but not the deoxygenated hemoglobin. On the other hand, the dermatologists recruited in this study were inclined to rate higher scores on the "erythema" category as skin's deoxygenated hemoglobin level was higher. Thus, the Mexameter derived erythema readings may not be coherent with the PASI erythema scores. Further, the Corneometer derived skin capacitance readings were well correlated to the PASI "desquamation" and "thickness" scores, while the PASI "desquamation" evaluation was a dominating factor contributing to the DRS deduced water-protein binding status. We conclude that the DRS method could be a valuable addition to existing skin capacitance/reflectance measurement systems and the PASI scoring system toward achieving a more efficient and objective clinical psoriasis vulgaris severity evaluation.


Assuntos
Psoríase , Eritema/diagnóstico , Eritema/patologia , Hemoglobinas , Humanos , Psoríase/diagnóstico , Psoríase/patologia , Índice de Gravidade de Doença , Água
14.
Acta Biomater ; 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35500813

RESUMO

To effectively treat diabetic wounds, the development of versatile medical dressings that can long-term regulate blood glucose and highly effective anti-oxidative stress, antibacterial and anti-inflammatory are critical. Here, an all-in-one CO gas-therapy-based versatile hydrogel dressing (ICOQF) was developed via the dynamic Schiff base reaction between the amino groups on quaternized chitosan (QCS) and the aldehyde groups on benzaldehyde-terminated F108 (F108-CHO) micelles. CORM-401 (an oxidant-sensitive CO-releasing molecules) was encapsulated in the hydrophobic core of F108-CHO micelles and insulin was loaded in the three-dimensional network structure of ICOQF. The dynamic Schiff base bonds not only endowed ICOQF with good tissue adhesion, injectability and self-healing, but also gave it sustained and controllable insulin release ability. In addition, ICOQF could quickly generate CO in inflamed wound tissue by consuming reactive oxygen species. The generated CO could effectively anti-oxidative stress by activating the expression of heme oxygenase; antibacterial by inducing the rupture of bacterial cell membranes and mitochondrial dysfunction and inhibiting the synthesis of adenosine triphosphate; and anti-inflammatory by inhibiting the proliferation of activated macrophages and promoting the polarization of the M1 phenotype to the M2 phenotype. Due to these outstanding properties, ICOQF significantly promoted the healing of STZ-induced MRSA-infected diabetic wounds accompanied by good biocompatibility. This study clearly shows that ICOQF is a versatile hydrogel dressing with great application potential for the management of diabetic wounds. STATEMENT OF SIGNIFICANCE: The development of some versatile hydrogel dressings that can not only provide a prolonged and controlled insulin release property but also utilize a non-antibiotic treatment modality for highly effective antibacterial, anti-inflammatory, and anti-oxidative stress effects is vital for the successful treatment of diabetic wounds. Herein, we developed an all-in-one CO gas-therapy-based versatile hydrogel dressing (ICOQF) with sustained and controllable insulin release abilities. Moreover, ICOQF could not only quickly release CO in the inflamed wound tissue by consumption of reactive oxygen species but also utilize the generated CO to highly effectively anti-oxidative stress, antibacterial, and anti-inflammatory. ICOQF therapy substantially promoted the healing of STZ-induced MRSA-infected diabetic wounds. Overall, this work provides a multifunctional hydrogel dressing for the management of diabetic wounds.

15.
Nat Commun ; 13(1): 2364, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501352

RESUMO

Negative pressure has emerged as a powerful tool to tailor the physical properties of functional materials. However, a negative pressure control of spin-phonon coupling for engineering magnetism and multiferroicity has not been explored to date. Here, using uniform three-dimensional strain-induced negative pressure in nanocomposite films of (EuTiO3)0.5:(MgO)0.5, we demonstrate an emergent multiferroicity with magnetodielectric coupling in EuTiO3, matching exactly with density functional theory calculations. Density functional theory calculations are further used to explore the underlying physics of antiferromagnetic-paraelectric to ferromagnetic-ferroelectric phase transitions, the spin-phonon coupling, and its correlation with negative pressures. The observation of magnetodielectric coupling in the EuTiO3 reveals that an enhanced spin-phonon coupling originates from a negative pressure induced by uniform three-dimensional strain. Our work provides a route to creating multiferroicity and magnetoelectric coupling in single-phase oxides using a negative pressure approach.

16.
J Cell Physiol ; 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35491506

RESUMO

Histone deacetylases (HDACs) play important roles in the repression of gene expression. Our previous study revealed that HISTONE DEACETYLASE 9 (HDA9) interacts with ELONGATED HYPOCOTYL 5 (HY5) and is involved in regulating plant autophagy in response to the light-to-dark transition and nitrogen starvation. In this study, we observed that the hda9-1 and hy5-215 single mutants flowered earlier compared with the wild-type Col-0; in addition, the hda9-1 hy5-215 double mutant flowered earlier than each single mutant. The expression of several positive flowering time genes was upregulated in the hda9-1, hy5-215, and hda9-1 hy5-215 mutants. Chromatin immunoprecipitation analysis demonstrated that HDA9 and HY5 bound directly to the promoter regions of PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) and CONSTANS-LIKE 5 (COL5) and repressed their expression through H3K9 and H3K27 deacetylation. Taken together, our results reveal the epigenetic mechanism explaining how the HDA9-HY5 module functions in controlling flowering time.

17.
J Chem Inf Model ; 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35579568

RESUMO

Protein-ligand scoring functions are widely used in structure-based drug design for fast evaluation of protein-ligand interactions, and it is of strong interest to develop scoring functions with machine-learning approaches. In this work, by expanding the training set, developing physically meaningful features, employing our recently developed linear empirical scoring function Lin_F9 (Yang, C. J. Chem. Inf. Model. 2021, 61, 4630-4644) as the baseline, and applying extreme gradient boosting (XGBoost) with Δ-machine learning, we have further improved the robustness and applicability of machine-learning scoring functions. Besides the top performances for scoring-ranking-screening power tests of the CASF-2016 benchmark, the new scoring function ΔLin_F9XGB also achieves superior scoring and ranking performances in different structure types that mimic real docking applications. The scoring powers of ΔLin_F9XGB for locally optimized poses, flexible redocked poses, and ensemble docked poses of the CASF-2016 core set achieve Pearson's correlation coefficient (R) values of 0.853, 0.839, and 0.813, respectively. In addition, the large-scale docking-based virtual screening test on the LIT-PCBA data set demonstrates the reliability and robustness of ΔLin_F9XGB in virtual screening application. The ΔLin_F9XGB scoring function and its code are freely available on the web at (https://yzhang.hpc.nyu.edu/Delta_LinF9_XGB).

18.
Int J Mol Sci ; 23(9)2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35563472

RESUMO

WRINKLED1 (WRI1), an APETALA2/ethylene-responsive-element-binding protein (AP2/EREBP) subfamily transcription factor, plays a crucial role in the transcriptional regulation of plant fatty acid biosynthesis. In this study, GmWRI1a was overexpressed in the soybean cultivar 'Dongnong 50' using Agrobacterium-mediated transformation to generate three transgenic lines with high seed oil contents. PCR and Southern blotting analysis showed that the T-DNA was inserted into the genome at precise insertion sites and was stably inherited by the progeny. Expression analysis using qRT-PCR and Western blotting indicated that GmWRI1a and bar driven by the CaMV 35S promoter were significantly upregulated in the transgenic plants at different developmental stages. Transcriptome sequencing results showed there were obvious differences in gene expression between transgenic line and transgenic receptor during seed developmental stages. KEGG analysis found that the differentially expressed genes mainly annotated to metabolic pathways, such as carbohydrated metabolism and lipid metabolism. A 2-year single-location field trial revealed that three transgenic lines overexpressing GmWRI1a (GmWRI1a-OE) showed a stable increase in seed oil content of 4.97-10.35%. Importantly, no significant effect on protein content and yield was observed. Overexpression of GmWRI1a changed the fatty acid composition by increasing the linoleic acid (C18:2) content and decreasing the palmitic acid (C16:0) content in the seed. The three GmWRI1a-OE lines showed no significant changes in agronomic traits. The results demonstrated that the three GmWRI1a overexpression lines exhibited consistent increases in seed oil content compared with that of the wild type and did not significantly affect the seed yield and agronomic traits. The genetic engineering of GmWRI1a will be an effective strategy for the improvement of seed oil content and value in soybean.

19.
J Colloid Interface Sci ; 623: 63-76, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35569224

RESUMO

Catalytic hydrogenation reduction provides a potential route to detoxify nitro compounds. Spinel NiFe2O4 (NiFeO) serves as a natural abundance and low-cost catalyst but suffers from low catalytic activity due to poor redox nature and limited active sites. Herein, defective MNiFeO (M = Cu, Zn, Co, Mn) nanorods (NRs) were synthesized by pyrolysis of cation-exchanged Fe2Ni-MOFs. The introduction of M modified the electronic structure of NiFeO and thus accelerated the electron transfer and proton transport in the hydrogenation of nitro aromatics. CuNiFeO exhibited the highest catalytic activity with a turn frequency of 2.89 × 105h-1, giving 308- and 422-fold larger than that of NiFeO-Vo and NiFeO in the reduction of 4-nitrophenol (4-NP). CuNiFeO NRs also presented exceptional performances in the reduction of the other nitroarenes. The remarkable improvement in activity of mesoporous CuNiFeO may be attributed to its ternary composites, and increased oxygen vacancies. This work not only provides a simple route to constructing mesoporous MNiFeO NRs with oxygen vacancies, but also further discusses the effects of metal component and oxygen defects in the catalytic reduction of 4-NP.

20.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35560430

RESUMO

The mammalian kidneys play a critical role in regulation of electrolyte balance and blood pressure. At least 14 kidney tubule segments are described, of which the distal convoluted tubule (DCT) is the shortest; yet this short segment plays a crucial role in a variety of homeostatic processes, including sodium, potassium, calcium and magnesium handling. The DCT is morphologically and functionally heterogeneous and comprises DCT1 and DCT2. A "shotgun" single-cell RNA sequencing (scRNAseq) approach transcriptionally profiles all cells from a piece of kidney tissue, which may allow abundant cell types to overwhelm minority cell types, such as DCT, thereby masking their complex heterogeneity. Recently, Chen et al. used the targeted scRNAseq analysis and identified 6 populations of DCT1 cells; yet the DCT2 was not well represented and therefore poorly resolved. To understand the heterogeneity within the DCT2 population, we used "Isolation of Nuclei TAgged in specific Cell Types" (INTACT), which fluorescently labels nuclei from genetically targetable cells. Combined with the NCC (sodium chloride cotransporter)-driven inducible Cre recombinase, DCT nuclei can be enriched using Fluorescence-Activated Nuclei Sorting (FANS). Female NCC-Cre-INTACT mice were treated with Tamoxifen to induce expression of the GFP-tagged SUN1, a nuclear membrane protein. Mice were provided either normal (NK) or potassium deficient diet (KD) for 4 days and kidneys were harvested. Nuclei from one kidney cortex were isolated and 10,000 GFP-positive nuclei from each mouse were input into 10X Genomics Chromium Controller and the libraries were sequenced using NovaSeq. The resulting dataset was analyzed using Seurat to determine the number of populations and their identities using the UMAP algorithm for analysis and visualization. After data quality control, we detected 24,054 genes across 70,233 cells. Unbiased clustering and UMAP visualization revealed 12 clusters, with most cells from the DCT (78%) indicating the success of the enrichment process. Among those, 70% of the cells were from DCT1 and 30% from DCT2. There was clear separation of DCT1 from DCT2, with DCT1 enriched in Trpm7, Egf, Umod and Erbb4, and DCT2 in Slc8a1, Calb1, S100g, Trpv5, and Scnn1g. After further analysis of the DCT2 population, we identified two specialized populations, DCT2-α and DCT2-ß. The DCT2-α is enriched in NCC, magnesium and calcium-related genes (Slc12a3, Wnk1, Slc8a1, Calb1, Trpm6, etc.) whereas DCT2-ß is enriched in mineralocorticoid receptors and epithelial sodium channel-related genes (Nr3c2, Klk1, Scnn1b, Scnn1g, etc.), indicating that DCT2-α is more similar to DCT1 and DCT2-ß to collecting duct. Four-day KD treatment decreased the Klk1, Scnn1b and Scnn1g expression levels in DCT2-ß, indicating that some DCT2 cells may reprogram to retain potassium in response to the short-term potassium deficiency. Our results suggest that DCT2 cells fall into specialized populations that likely serve different functions in electrolyte handling. The DCT2 is plastic and can transform from potassium excretion to potassium sparing in response to dietary potassium restriction to maintain electrolyte balance.

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