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1.
Brief Bioinform ; 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34849565

RESUMO

Gene transcription and protein translation are two key steps of the 'central dogma.' It is still a major challenge to quantitatively deconvolute factors contributing to the coding ability of transcripts in mammals. Here, we propose ribosome calculator (RiboCalc) for quantitatively modeling the coding ability of RNAs in human genome. In addition to effectively predicting the experimentally confirmed coding abundance via sequence and transcription features with high accuracy, RiboCalc provides interpretable parameters with biological information. Large-scale analysis further revealed a number of transcripts with a variety of coding ability for distinct types of cells (i.e. context-dependent coding transcripts), suggesting that, contrary to conventional wisdom, a transcript's coding ability should be modeled as a continuous spectrum with a context-dependent nature.

2.
Arterioscler Thromb Vasc Biol ; : ATVBAHA121316847, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34809445

RESUMO

OBJECTIVE: While the risk of acute coronary events has been associated with biological variability of circulating cholesterol, the association with variability of other atherogenic lipids remains less understood. We evaluated the longitudinal variability of 284 lipids and investigated their association with asymptomatic coronary atherosclerosis. Approach and Results: Circulating lipids were extracted from fasting blood samples of 83 community-sampled symptom-free participants (age 41-75 years), collected longitudinally over 6 months. Three types of coronary plaque volume (calcified, lipid-rich, and fibrotic) were quantified using computed tomography coronary angiogram. We first deconvoluted between-subject (CVg) and within-subject (CVw) lipid variabilities. We then tested whether the mean lipid abundance was different across groups categorized by Framingham risk score and plaques phenotypes (lipid-rich, fibrotic, and calcified). Last, we investigated whether visit-to-visit variability of each lipid was associated with plaque burden. Most lipids (72.5%) exhibited higher CVg than CVw. Among the lipids (N=145) with 1.2-fold higher CVg than CVw, 26 species including glycerides and ceramides were significantly associated with Framingham risk score and the 3 plaque phenotypes (false discovery rate <0.05). In an exploratory analysis of person-specific visit-to-visit variability without multiple-comparisons testing, high variability of 3 lysophospholipids (lysophosphatidylcholines 16:0, 18:0, and O-18:1) were associated with lipid-rich and fibrotic (noncalcified) plaque volume while high variability of diacylglycerol 18:1_20:0, triacylglycerols 52:2, 52:3, and 52:4, ceramide d18:0/20:0, dihexosylceramide d18:1/16:0, and sphingomyelin 36:3 were associated with calcified plaque volume. CONCLUSIONS: High person-specific longitudinal variation of specific nonsterol lipids are associated with the burden of subclinical coronary atherosclerosis. Larger studies are needed to confirm these exploratory findings.

3.
Front Behav Neurosci ; 15: 747733, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803624

RESUMO

Tai Chi Chuan (TCC) is assumed to exert beneficial effects on functional brain activity and cognitive function in elders. Until now, empirical evidence of TCC induced intra-regional spontaneous neural activity and inhibitory control remains inconclusive. Whether the effect of TCC is better than that of other aerobic exercises is still unknown, and the role of TCC in younger adults is not yet fully understood. Here we used resting-state functional MRI (fMRI) to investigate the effects of 8-week TCC (n = 12) and brisk walking (BW, n = 12) on inhibitory control and fractional amplitude of low-frequency fluctuations (fALFF). The results found that TCC had significant effects on inhibitory control performance and spontaneous neural activity that were associated with significantly increased fALFF in the left medial superior frontal gyrus (Cohen's d = 1.533) and the right fusiform gyrus (Cohen's d = 1.436) and decreased fALFF in the right dorsolateral superior frontal gyrus (Cohen's d = 1.405) and the right paracentral lobule (Cohen's d = 1.132).TCC exhibited stronger effects on spontaneous neural activity than the BW condition, as reflected in significantly increased fALFF in the left medial superior frontal gyrus (Cohen's d = 0.862). There was a significant positive correlation between the increase in fALFF in the left medial superior frontal gyrus and the enhancement in inhibitory control performance. The change in fALFF in the left medial superior frontal gyrus was able to explain the change in inhibitory control performance induced by TCC. In conclusion, our results indicated that 8 weeks of TCC intervention could improve processing efficiency related to inhibitory control and alter spontaneous neural activity in young adults, and TCC had potential advantages over BW intervention for optimizing spontaneous neural activity.

4.
Zootaxa ; 5040(2): 238-246, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34811044

RESUMO

We studied the relationship of the genera Loxoblemmus Saussure, 1877 and Asonicogryllus He, 2019 by reconstructing the phylogenetic tree based on 2 mitochondrial genes and 2 ribosomal genes. The result shows that Loxoblemmus is paraphyletic. Thus, we place Asonicogryllus as a subgenus of Loxoblemmus. Meanwhile, we report a new species of Asonicogryllus, L. (A.) bronzus He sp. nov. The new species is similar to L. (A.) kwanghua, but it has well developed forewings and hindwings. The type specimens are deposited in the Museum of Biology, East China Normal University (ECNU).


Assuntos
Gryllidae , Distribuição Animal , Estruturas Animais , Animais , Tamanho Corporal , China , Gryllidae/genética , Tamanho do Órgão , Filogenia
5.
Antibiotics (Basel) ; 10(11)2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34827316

RESUMO

Drug efflux pumps are one of the major elements used by antibiotic-resistant bacteria. Efflux pump inhibitors (EPIs) are potential therapeutic agents for adjunctive therapy, which can restore the activity of antibiotics that are no longer effective against pathogens. This study evaluated the seaweed compound diphenylmethane (DPM) for its EPI activity. The IC50 and modulation results showed that DPM has no antibacterial activity but can potentiate the activity of antibiotics against drug-resistant E. coli. Time-kill studies reported that a combination of DPM and erythromycin exhibited greater inhibitory activity against drug-resistant Escherichia coli. Dye accumulation and dye efflux studies using Hoechst 33342 and ethidium bromide showed that the addition of DPM significantly increased dye accumulation and reduced dye efflux in drug-resistant E. coli, suggesting its interference with dye translocation by an efflux pump. Using MALDI-TOF, it was observed that the addition of DPM could continuously reduce antibiotic efflux in drug-resistant E. coli. Additionally, DPM did not seem to damage the E. coli membranes, and the cell toxicity test showed that it features mild human-cell toxicity. In conclusion, these findings showed that DPM could serve as a potential EPI for drug-resistant E. coli.

6.
Food Funct ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34825691

RESUMO

Objective: This study aimed to elucidate the pharmacological effects of sesamin (Ses) and its mechanism of action towards PM2.5-induced cardiovascular injuries. Method: Forty Sprague Dawley (SD) rats were randomly divided into five groups: a saline control group; a PM2.5 exposure group; and low-, middle-, and high-dose Ses pretreatment groups. The SD rats were pretreated with different concentrations of Ses for 21 days. Afterward, the rats were exposed to ambient PM2.5 by intratracheal instillation every other day for a total of three times. The levels of inflammatory markers, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and interleukin-6 (IL-6), and indicators related to oxidative responses, such as total superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA), were measured in the blood and heart. The expression of ferroptosis-related proteins in heart tissues was determined via western blot and immunohistochemistry. Results: Ses pretreatment substantially ameliorated cardiovascular injuries in rats as evidenced by the decrease in the pathological score and collagen area. The decreased levels of SOD, GSH, and GSH-Px in the heart and serum were inhibited by Ses. In addition, Ses not only notably increased the activity of antioxidant enzymes but also reduced the levels of MDA, CK, LDH, CK-MB, IL-6, TNF-α, IL-1ß, and IL-6. Furthermore, Ses pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Conclusion: Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis. Therefore, Ses pretreatment may be a novel strategy for the prevention and treatment of PM2.5-induced cardiovascular injury.

7.
Br J Clin Pharmacol ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34837258

RESUMO

BACKGROUND AND PURPOSE: Rivaroxaban is a viable anticoagulant for the management of cancer associated venous thromboembolism (CA-VTE). A previously verified physiologically-based pharmacokinetic (PBPK) model of rivaroxaban established how its multiple pathways of elimination via both CYP3A4/2J2-mediated hepatic metabolism and organic anion transporter 3 (OAT3)/P-glycoprotein-mediated renal secretion predisposes rivaroxaban to drug-drug-disease interactions (DDDIs) with clinically relevant protein kinase inhibitors (PKIs). We proposed the application of PBPK modelling to prospectively interrogate clinically significant DDIs between rivaroxaban and PKIs (erlotinib and nilotinib) for dose adjustments in CA-VTE. EXPERIMENTAL APPROACH: The inhibitory potencies of the PKIs on CYP3A4/2J2-mediated metabolism of rivaroxaban were characterized. Using prototypical OAT3 inhibitor ketoconazole, in vitro OAT3 inhibition assays were optimized to ascertain the in vivo relevance of derived transport inhibitory constants (Ki ). Untested DDDIs between rivaroxaban and erlotinib or nilotinib were simulated. KEY RESULTS: Mechanism-based inactivation (MBI) of CYP3A4-mediated rivaroxaban metabolism by both PKIs and MBI of CYP2J2 by erlotinib were established. The importance of substrate specificity and nonspecific binding to derive OAT3-inhibitory Ki values of ketoconazole and nilotinib for the accurate prediction of interactions was illustrated. When simulated rivaroxaban exposure variations with concomitant erlotinib and nilotinib therapy were evaluated using published dose-exposure equivalence metrics and bleeding risk analyses, dose reductions from 20 mg to 15 mg and 10 mg in normal and mild renal dysfunction, respectively, were warranted. CONCLUSION AND IMPLICATIONS: We established a PBPK-DDDI model to prospectively evaluate clinically relevant interactions between rivaroxaban and PKIs for the safe and efficacious management of CA-VTE.

8.
Front Oncol ; 11: 751758, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765557

RESUMO

Post-radiation soft tissue sarcomas (PRSTSs) are rare secondary malignancies. In this report, we describe the clinical presentation of a 52-year-old woman who underwent postmastectomy radiation therapy (PMRT) for left-sided breast cancer 2.7 years ago and presented with a left internal mammary mass and left interpectoral nodule on computed tomography. On further evaluation, she was diagnosed with internal mammary rhabdomyosarcoma and interpectoral nodal breast cancer relapse, and was treated with chemotherapy, followed by surgery and endocrine therapy. She developed left pleural metastases and is currently receiving targeted therapy. Internal mammary rhabdomyosarcomas are rare among PRSTSs and pose a diagnostic challenge for patients with breast cancer. Histological evaluation is important for the differential diagnosis of breast cancer relapses with secondary malignancies. The management of post-radiation thoracic rhabdomyosarcomas is challenging, and the prognosis is poor.

9.
J Psychosom Res ; 152: 110680, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34826656

RESUMO

OBJECTIVE: Few studies have evaluated the association between children's exposure to environmental tobacco smoke (ETS) in early life (during pregnancy, from birth to one year and from one to three years) and autistic-like behaviors. This study aimed to explore this association. METHODS: This cross-sectional study analyzed data collected in 2017 as part of the Longhua Child Cohort Study. Autistic-like behaviors were measured using the Autism Behavior Checklist (ABC). Data on ETS exposure and autistic-like behaviors of children were collected via self-administered questionnaires completed by the mothers. Multivariate logistic regression models were undertaken to assess the associations. RESULTS: Of the 65,243 participants included in this study, 1958 children met criteria for having autistic-like behaviors. The results showed that children were more likely to exhibit autistic-like behaviors when they were exposed to ETS in early life (AOR = 1.38; 95% CI = 1.26-1.52), compared to preschoolers without ETS exposure at any period of their early life. Compared with their unexposed counterparts, children who were exposed to ETS during gestation (AOR = 1.42; 95% CI = 1.29-1.57), or from birth to one year old (AOR = 1.42; 95% CI = 1.19-1.69) had significantly increased risk of autistic-like behaviors. In addition, with the increase in duration of exposure and average number of cigarettes smoked in the child's immediate environment, the risk of autistic-like behaviors increased. CONCLUSION: Our study indicated that children's ETS exposure in early life was significantly associated with autistic-like behaviors. When children's exposure to cigarettes in early life increased in duration and number, the likelihood of the presence of autistic-like behaviors was higher.

10.
PhytoKeys ; 184: 19-26, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759725

RESUMO

Saxifragaviridiflora, a remarkable new species of the genus Saxifragasect.Irregulares (Saxifragaceae) from Guangxi, is described and illustrated herein. This new species morphologically differs from all known S.sect.Irregulares taxa by its greenish petals, verruculose sepals, and thick leathery leaf blade abaxially scarlet with white spots.

11.
Asian J Androl ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34782549

RESUMO

To analyze the performance of the Prostate Health Index (phi) and its derivatives for predicting Gleason score (GS) upgrading between prostate biopsy and radical prostatectomy (RP) in the Chinese population, an observational, prospective RP cohort consisting of 351 patients from two medical centers was established from January 2017 to September 2020. Pathological reclassification was determined by the Gleason Grade Group (GG). The area under the receiver operating characteristic curve (AUC) and logistic regression (LR) models were used to evaluate the predictive performance of predictors. In clinically low-risk patients with biopsy GG ≤ 2, phi (odds ratio [OR] = 1.80, 95% confidence interval [95% CI]: 1.14-2.82, P = 0.01) and its derivative phi density (PHID; OR = 2.34, 95% CI: 1.30-4.20, P = 0.005) were significantly associated with upgrading to GG ≥ 3 after RP, and the results were confirmed by multivariable analysis. Similar results were observed in patients with biopsy GG of 1 for the prediction of upgrading to RP GG ≥ 2. Compared to the base model (AUC = 0.59), addition of the phi or PHID could provide additional predictive value for GS upgrading in low-risk patients (AUC = 0.69 and 0.71, respectively, both P < 0.05). In conclusion, phi and PHID could predict GS upgrading after RP in clinically low-risk patients.

12.
Indoor Air ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34738663

RESUMO

Indoor air pollution is a recognized risk factor for a range of negative health outcomes. This study aimed to investigate the association between maternal prenatal exposure to indoor air pollution and the presence of autistic-like behaviors among preschool children. Data were obtained from the Longhua Child Cohort Study in 2017, in which we enrolled a total of 65 317 preschool children. Associations between maternal exposure to four sources of indoor air pollution (e.g., cooking, environmental tobacco smoke (ETS), mosquito coils, and home decoration) during pregnancy and preschool children's autistic traits were analyzed using multivariate logistic regression. Our results showed that maternal exposure to indoor air pollution from four different sources during pregnancy was associated with the presence of children's autistic-like behaviors. There was dose-response relationship between the accumulative exposure to the four different indoor air pollution sources and the risk of autistic-like behaviors. Furthermore, we found a significant additive interaction between prenatal exposure to both cooking and mosquito coil incense on the risk of autistic-like behaviors. Maternal prenatal exposure to the indoor air pollution from four sources might increase with the risk of autistic-like behaviors being present among preschool children, with an additive interaction effect between some pollution sources.

13.
Sci Rep ; 11(1): 21775, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741126

RESUMO

The West Philippine Basin (WPB) has started opening at ~ 58 Ma and ceased spreading at ~ 33 Ma, developing a fast spreading (~ 44 mm/yr half-spreading rate) magmatic episode between 58 and 41 Ma and the second amagmatic episode between 41 and 33 Ma. The occurrence of the first stage of spreading is closely related to the Oki-Daito mantle plume and related Benham Rise (BR) and Urdaneta Plateau (UP) activity. To the east of the Luzon-Okinawa Fracture Zone (LOFZ), BR was the most active volcanism from 48 to 41 Ma. The geomagnetic ages on both sides of the LOFZ have been determined; however, their causal relationship and evolution in the WPB remain unclear. In this study, we performed integrated analyses of multichannel seismic data and swath bathymetry data for the area to the west of the LOFZ. To the west of the LOFZ, the Gagua Rise (GR), is identified by a high residual free-air gravity anomaly, volcanic seamount chains and an overlapping spreading center. The GR is located at magnetic isochrons C20/C22 (50 to 44 Ma) and shows a thick oceanic crust of at least 12.7 km. We first propose an oceanic plateau named Great Benham Rise (GBR) which includes GR, UP and BR. We infer that the GR was a portion of the GBR since ~ 49 Ma and was separated from the GBR at ~ 41 Ma by the right-lateral LOFZ motion. Later, the relict GBR magmatism only continued in the area to the east of the LOFZ. Overall, the GBR dominates the spreading history of the WPB.

14.
Inorg Chem ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34793150

RESUMO

Improved methods for the synthesis of KB3H8, NH3B3H7, and N-alkyl analogues of NH3B3H7 have been developed based on previous works. KB3H8 was synthesized by the reaction of metallic potassium (K) with borane dimethyl sulfide ((CH3)2S·BH3) with high yield and atom-economy. In the preparation of NH3B3H7 and its N-alkyl analogues, KB3H8 served as a starting material and was converted to THF·B3H7 first through reactions with HCl diethyl ether solution or oxidation agent CoCl2. Then, the formed THF·B3H7 in situ reacted with the corresponding ammonia or amines to form the amine borane final products. This work paves an alternative way for preparing organic-inorganic hybrid materials containing B, N, and C atoms.

15.
ACS Synth Biol ; 10(11): 2833-2841, 2021 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-34734710

RESUMO

Efficient enabling technology is required for synthetic biology in Streptomyces due to its natural product reservoir. Though the CRISPR-Cas9 system is powerful for genome editing in this genus, the proposed Cas9 toxicity has limited its application. Here on the basis of previous inducible Cas9 expression at the transcriptional and translational levels coupled with atpD overexpression, a Cas9 cognate inhibitor AcrIIA4 was further introduced to fine-tune the Cas9 activity. In both laboratory and industrial Streptomyces species, we showed that, compared to the constitutively expressed Cas9, incorporating AcrIIA4 increased the conjugation efficiency from 700- to 7000-fold before induction, while a comparable 65%-90% editing efficiency was obtained even on multiple loci for simultaneous deletion after Cas9 expression was induced, along with no significant off-targets. Thus, AcrIIA4 could be a modulator to control Cas9 activity to significantly improve genome editing, and this new toolkit would be widely adaptable and fasten genetic engineering in Streptomyces.

16.
Gynecol Oncol ; 163(3): 552-556, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34674890

RESUMO

OBJECTIVE: To describe the incidence, complications, and trends associated with ureteral surgeries on a gynecologic oncology service in the context of a fellowship training program over a 24-year period. METHODS: We conducted a retrospective cohort analysis of ureteral surgeries by gynecologic oncologists at either Moffitt Cancer Center or Tampa General Hospital from 1997 to 2020. Patient characteristics, predisposing factors, location and type of injury, repair method, postoperative management and complications were abstracted from the medical record. The recent cohort (2005-2020) was compared to our prior series (1997-2004). RESULTS: Eighty-eight cases were included. The average number of ureteral surgeries per year decreased from 5.75 (1997-2004) to 2.63 (2005-2020). Of 46 iatrogenic injuries, 45 were recognized and repaired intraoperatively. Ureteral transection was the most common type (85% [39 of 46]) and the distal 5 cm was the most common location of injury (63% [29 of 46]). Ureteroneocystostomy was the most common method of repair (83% [73 of 88]). Postoperative management, including stenting and imaging, has not changed significantly. Length of urinary catheter usage decreased in the recent cohort without associated complications. Five patients had major postoperative complications and 4 involved the urinary tract. Of those with follow-up, 96% (66 of 69) of ureteroneocystostomies and 75% (9 of 12) of ureteroureterostomies had radiologically normal urinary tracts. CONCLUSIONS: Ureteral surgery is necessary in the case of injury or involvement with invasive disease. There has been a decrease in number of procedures. Ureteroneocystostomy has remained the most common method of reconstruction for both injury and resection with acceptable postoperative complication rates.

17.
Gynecol Oncol Rep ; 38: 100862, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34621945

RESUMO

Objective: To compare perioperative outcomes of the elderly versus non-elderly patients on ERPs undergoing laparotomy for gynecologic surgery. Methods: From January 2016 to June 2017, patients undergoing elective laparotomies for gynecologic surgery were enrolled in a perioperative ERP protocol. Outcomes were compared between the elderly (age ≥ 70 years) and the non-elderly (age ≤ 69 years). Primary outcomes were length of stay and perioperative complication rates. Comparisons were performed using chi-squared tests or Fisher's exact tests for categorical data and Student's t-test or Wilcoxon rank-sum tests for continuous variables, with p < 0.05 for significance. Results: One hundred eighty-nine patients were enrolled in the study, including 16 patients ≥ 70 years old. The median age was 75 years for the elderly and 45 years for the non-elderly. Elderly patients were more likely to have more complex surgery and longer operative times (absolute median difference of 39 min). Despite the increasing complexity of surgical procedures for elderly patients, there were no statistically significant differences in serious inpatient complications (Clavien-Dindo score 3A or greater), pain and nausea scores, 30-day complications and readmission rates. Elderly patients had a longer median length of stay compared to non-elderly patients by one day (p < 0.001), however, this was not statistically significant on multivariate analysis. Conclusion: In our series, elderly patients on the ERP had similar rates of complications and readmission when compared to non-elderly patients, despite undergoing more complex surgeries. This suggests that ERP may be feasible and safe in the elderly population undergoing elective gynecologic laparotomy.

18.
Front Psychol ; 12: 712441, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603137

RESUMO

This study aims to explore the longitudinal mediation effects of college students' perceived task value (PTV) between perceived teacher enthusiasm (PTE) and class-related boredom (CB). We conducted a longitudinal survey among college students from five colleges at the second (T1), sixth (T2), tenth (T3), and fourteenth week (T4) in a semester, and overall 1,371 students completed all the measurements. In the survey, a battery of questionnaires was used to measure the students' PTE, perception of task difficulty, perception of task value, and CB. At T1, boredom proneness was measured as a control variable. Analysis of the longitudinal data showed that after controlling for the effects of boredom proneness and perceived task difficulty, students' PTE was a significant predictor of CB, and students' PTV played a significant mediating role in this causation relationship. The study supported the importance of the control-value theory in explaining the mitigating effect of students' PTE on CB, especially highlighting the role of PTV.

19.
J Bone Miner Res ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34668226

RESUMO

Osteopetrosis is a group of rare inherited skeletal disorders characterized by a marked increase in bone density due to deficient bone resorption. Pathogenic variants in several genes involved in osteoclast differentiation and/or function have been reported to cause osteopetrosis. Solute carrier family 4 member 2 (SLC4A2, encoding anion exchanger 2) plays an important role in osteoclast differentiation and function by exchange of Cl- with HCO3 - . Biallelic Slc4a2 loss-of-function mutations in mice and cattle lead to osteopetrosis with osteoclast deficiency; however, pathogenic SLC4A2 variants in humans have not been reported. In this study, we describe a patient with autosomal recessive osteopetrosis due to biallelic pathogenic variants in SLC4A2. We identified novel compound heterozygous variants in SLC4A2 (NM_003040.4: c.556G>A [p.A186T] and c.1658T>C [p.V553A]) by exome sequencing. The measurement of intracellular Cl- showed that the variants decrease the anion exchange activity of SLC4A2. The impact of the variants on osteoclast differentiation was assessed by a gene knockout-rescue system using a mouse macrophage cell line, RAW 264.7. The Slc4a2-knockout cells show impaired osteoclastogenesis, which was rescued by the wild-type SLC4A2, but not by the mutant SLC4A2s. Immunofluorescence and pit assay revealed that the mutant SLC4A2s leads to abnormal podosome belt formation with impaired bone absorption. This is the first report on an individual affected by SLC4A2-associated osteopetrosis (osteopetrosis, Ikegawa type). With functional studies, we prove that the variants lead to SLC4A2 dysfunction, which altogether supports the importance of SLC4A2 in human osteoclast differentiation. © 2021 American Society for Bone and Mineral Research (ASBMR).

20.
Medicine (Baltimore) ; 100(39): e27323, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596133

RESUMO

BACKGROUND: Mild cognitive impairment (MCI), as a common neurodegenerative aging disease representing an intermediate stage between normal cognitive functioning and dementia, poses an excessive burden on health care. The clinical benefit of Chinese herbal medicines (CHMs) for MCI remains inconclusive. This study is aimed at evaluating the efficacy and acceptability of CHMs through meta-analysis and trial sequential analysis (TSA). METHODS: We applied extensive strategies on preliminary literature screening to identify relevant randomized controlled trials which meticulously compare any of CHMs interventions with placebo groups as monotherapy for MCI. The primary outcome of this study is the change of global cognitive function, and the secondary outcomes include assessments of activities of daily living, mood, and adverse events. Data synthesis, risk of bias assessment, sensitivity and subgroup analyses, and TSA will be conducted with application of Review Manager, Stata, and TSA software. The quality of the evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation instrument. INPLASY registration number: INPLASY202190006 (https://inplasy.com/inplasy-2021-9-0006/). RESULTS: This study will confirm the clinical efficacy and safety of CHMs when used in the treatment of patients with MCI. CONCLUSION: This study will provide reliable evidence and references for the selection of CHMs in therapy and future clinical research of MCI.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Atividades Cotidianas , Afeto/efeitos dos fármacos , China , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
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