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1.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35552346

RESUMO

Phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchanger 1 (P-Rex1) is a guanine nucleotide exchange factor for Rho GTPases downstream of G protein coupled receptors (GPCRs) and tyrosine kinases. It is primarily expressed in hematopoietic cells and brain. Its ectopic expression is reported in different cancers including breast, prostrate, skin, and ovarian cancers, making it a potential therapeutic target. P-Rex1 is a multi-domain protein consisting of a catalytic Dbl-homology (DH) domain, followed by a PH, two DEP, two PDZ, and an inositolpolyphosphate-4 phosphatase-like (IP4P) domain. P-Rex1 is regulated by PIP3, Gbg binding and phosphorylation via PKC and PKA. In unstimulated cells, P-Rex1 is autoinhibited by intradomain interactions with its catalytic DH domain. Previously, our lab had shown that first DEP (DEP1) domain plays a key role in inhibition of DH/PH-DEP1 exchange activity. However, there is no information available as how these domains are engaged in regulation of full length P-Rex1. In our current study, we addressed this gap by employing single particle cryo-electron microscopy (cryo-EM) complemented by SAXS, HDX-MS, and functional enzymatic assays to understand P-Rex1 regulation. A structure with the head group of PIP3 (IP4) bound to the PH domain revealed interactions between DH and DEP1 domain that would block GTPase access to DH domain by coercing a novel configuration of the DH-PH module. In addition, we observed that the IP4P domain was anchored to PH domain via a previously unrecognized FAT domain. Mutagenesis of residues involved in the DH-DEP1 interface led to activation, suggestive of inhibitory role of this interface. IP4 is a soluble second messenger signaling molecule which is reported to compete with PIP3 binding site in other proteins. Therefore, we tested whether it could regulate P-Rex1 in a similar manner and found that IP4 competes with PIP3 and negatively regulates P-Rex1 activity. Based on these observations, we propose that in unstimulated cell, P-Rex1 is autoinhibited by intradomain interactions between the DEP1 and DH and between the FAT and PH domains, and that inositol phosphate levels may add an additional layer of desensitization by opposing P-Rex1 membrane translocation and favoring a closed autoinhibited state.

2.
Nanomaterials (Basel) ; 12(9)2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35564322

RESUMO

This study characterizes and determines the corrosion resistance of Mn-Ce conversion coated LZ91 magnesium alloy that undergoes pretreatments. It is challenging to process large and curved workpieces in the industry because the geometric shapes are complex if they are mechanically ground. This study uses acid pickling instead of mechanical grinding, and a nitric acid solution is used for pickling. After pretreatments, the samples are immersed for 30 s in a conversion coating solution containing 0.1 M KMnO4 and 0.025 M Ce(NO3)3 with a pH of 1.5, as demonstrated in previous studies by the authors. The microstructure of the coating layer and electrochemical behavior of conversion coated samples exposed to 3.5 wt.% NaCl solution are studied. The corrosion behavior of Mn-Ce conversion coating specimens is determined using a salt spray test (SST). Scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDS), and X-ray photoelectron spectroscopy (XPS) are used to analyze the interface between the coating layer and the underlying magnesium substrate and to investigate the microstructure of the specimens. The roughness of the coatings is measured using 3D white light interferometry. The results show that the deteriorated area ratio for conversion coated LZ91 decreases to less than 5% after 72 h of SST exposure, and the corrosion resistance is improved 2.25 times with the Mn-Ce conversion coating on LZ91 magnesium alloy.

3.
Biomaterials ; 285: 121471, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35490561

RESUMO

Dissemination is an ominous feature of cancer to cause poor prognosis. Formation of tumor satellites is the first step, which is closely interdependent on the factors originating from surrounding niche. Because of lacking appropriate modeling, most studies focusing on cancer-environmental interaction depend on the static pathological analyses of specimens. Using the biomimicking system capable of inducing tumor satellite formation in vitro, the niche factors were explored for their influence on cancer budding. Our results demonstrated the real-time dynamic of tumor satellite formation of head and neck squamous cell carcinoma (HNSCC) that was significantly affected by these niche factors. Hypoxia reduced the incidence and migratory distance of HNSCC tumor satellites via decreasing the nuclear localization of intracellular domain of E-cadherin (iEcad) and ß-catenin. Three-dimensional (3D) architecture and collagen were essential for mediating hypoxia effects on nuclear translocation and signaling transduction of iEcad and ß-catenin in the HNSCC cells. The findings were further confirmed by the compatible in vivo findings of the cancer specimens. This approach revealed the effects of oxygen and extracellular matrices on tumor satellites. The cellular behaviors and molecular dynamics were along a phenotypic spectrum that conferred unique change for specific cancer populations in response to the altered microenvironment. The current study provides a platform to recapitulate the process of cancer budding, and a way to investigate the mutual interaction between the cancer cells and their surrounding microenvironment.

4.
J Phys Chem Lett ; 13(18): 4200-4206, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35511593

RESUMO

Mass-transport acceleration is essential toward enhanced electrocatalytic performance yet rarely recognized under irradiation, because light is usually reported to improve charge transfer. We studied laser-enhanced mass transport through the heterojunction between Ag and semiconductor Fe2O3 situated on graphene for oxygen reduction reaction. Because of the decreased mass-transport resistance by 59% under 405 nm laser irradiation, the current density can be enhanced by 180%, which is also supported by a theoretical calculation. This laser-enhanced mass transport was attributed to local photothermal heating and the near-field local enhancement. Easier desorption of OH- species occurring between the Fe and Ag centers under the laser accelerates the mass-transport centers.

5.
Am J Cancer Res ; 12(4): 1899-1911, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530282

RESUMO

Immune checkpoint inhibitors (ICIs) with atezolizumab plus bevacizumab are promising agents for unresectable hepatocellular carcinoma (HCC). We tried to guide the treatment based on recent developed CRAFITY score combining with on-treatment AFP response. Eighty-nine patients who received atezolizumab plus bevacizumab regardless of as a first-line therapy or not for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). The objective response rate (ORR) and disease control rate (DCR) were 25.0% and 65.5%, respectively. Multivariate analysis showed that low CRAFITY score (AFP<100 ng/ml or CRP<10 mg/l) and satisfactory AFP response at 6 weeks (≥75% decrease or ≤10% increase from baseline) were independent factors determining good overall survival (OS) (hazard ratio [HR]=0.143, P=0.002 & HR=0.337, P=0.031), progression-free survival (PFS) (HR=0.419, P=0.022 & HR=0.429, P=0.025) and good responder (odds ratio [OR]=1.763, P=0.044 & OR=3.881, P=0.011). Patients were further divided into three classes by combination of CRAFITY score and AFP response at 6 weeks [The CAR (CRAFITY score and AFP-Response) classification)]: low CRAFITY score with satisfactory AFP response at 6 weeks (class I), either high CRAFITY score or unsatisfactory AFP response at 6 weeks (class II) and high CRAFITY score together with unsatisfactory AFP response at 6 weeks (class III). ORR was 35.0%, 18.2%, and 0% in class I, II and III patients, respectively (overall P=0.034). Patients in the class I had the best OS and PFS, followed by class II and class III (median OS: not reached vs. 11.1 vs. 4.3 months, log-rank P<0.001; median PFS: 7.9 vs. 6.6 vs. 2.6 months, log-rank P=0.001). Combination CRAFITY score and AFP response at 6 weeks with AUROC predicts OS and tumor response to be 0.809 and 0.798, respectively, better than either CRAFITY score (0.771 & 0.750) or AFP response at 6 weeks (0.725 & 0.680) alone. In conclusions, the CAR classification which combining CRAFITY score and AFP response at 6 weeks provides a practical guidance for atezolizumab plus bevacizumab therapy in unresectable HCC patients.

6.
Am J Cancer Res ; 12(4): 1606-1620, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530291

RESUMO

Anti-Programmed cell Death protein 1 (Anti-PD1) or Programmed Death-Ligand 1 (PDL1) immune checkpoint inhibitors provide treatment options for advanced HCC patients with low response rates. Combination therapy is becoming a major issue to improve the unmet need. Proton beam radiotherapy (PBT) could effectively control the local tumor with a low-risk injury to peripheral liver parenchyma. We retrospectively reviewed the patients who have received PBT combined with anti-PD1/PDL1 to evaluate the efficacy and safety of the advanced HCC patients. This study reviewed 29 advanced HCC patients who have received PBT and anti-PD1/PDL1 during 2016 and 2019. All were Child-Pugh A and performance status 0-1. Seventeen patients (58.6%) had extrahepatic spreading. Concurrent PBT started during anti-PD1/PDL1 with a median of 96.6 grays equivalent dose. The PBT field covered all tumors in 13 (44.8%) patients under curative intent. Other patients (55.2%) received palliative PBT that covered only the principal tumors. All patients have completed the concurrent PBT protocol. The median anti-PD1/PDL1 duration was 3.9 months. After a median follow-up of 13.2 months, the rates of 1-year PBT infield tumor control, 1-year outfield tumor control, and overall response were 90.5%, 90.9%, and 61.5%, and 70.8%, 69.2%, and 43.8%, respectively for curative-intent and palliative-control PBT. Complete response was found in 4 (30.8%) curative-intent and 1 (6.3%) palliative-control patients. The median overall progression-free survival was 27.2 months for curative-intent patients and 15.9 months for palliative-control patients. The overall survival was non-reached for both groups. The ALBI grade and Child-Pugh score change at 3-month and 6-month after PBT initiation were nonsignificant. No unexpected adverse event occurred except nine patients (31.0%) had treatment-related adverse events higher than or equal to Grade 3, including 2 (6.9%) had a radiation-induced liver injury. PBT combined with anti-PD1/PDL1 was safe without unexpected adverse events. The concurrent therapy could effectively treat advanced HCC through sustained local tumor necrosis and effective systemic tumor control for the patients who received curative-intent or palliative-control PBT combined with anti-PD1/PDL1.

7.
Eur Radiol ; 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35499565

RESUMO

OBJECTIVES: Undiagnosed osteoporosis may lead to severe complications after spinal surgery. This study aimed to construct and validate a radiomic signature based on CT scans to screen for lumbar spine osteoporosis. METHODS: Using a stratified random sample method, 386 vertebral bodies were randomly divided into a training set (n = 270) and a test set (n = 116). A total of 1040 radiomics features were automatically retracted from lumbar spine CT scans using the 3D slicer pyradiomics module, and a radiomic signature was created. The sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of the Hounsfield and radiomics signature models were calculated. The AUCs of the two models were compared using the DeLong test. Their clinical usefulness was assessed using a decision curve analysis. RESULTS: Twelve features were chosen to establish the radiomic signature. The AUCs of the radiomics signature and Hounsfield models were 0.96 and 0.88 in the training set and 0.92 and 0.84 in the test set, respectively. According to the DeLong test, the AUCs of the two models were significantly different (p < 0.05). The radiomics signature model indicated a higher overall net benefit than the Hounsfield model, as determined by decision curve analysis. CONCLUSIONS: The CT-based radiomic signature can differentiate patients with/without osteoporosis prior to lumbar spinal surgery. Without additional medical cost and radiation exposure, the radiomics method may provide valuable information facilitating surgical decision-making. KEY POINTS: • The goal of the study was to evaluate the efficacy of a radiomics signature model based on routine preoperative lumbar spine CT scans in screening osteoporosis. • The radiomics signature model demonstrated excellent prediction performance in both the training and test sets. • This radiomics method may provide valuable information and facilitate surgical decision-making without additional medical costs and radiation exposure.

8.
Curr Psychol ; : 1-12, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35505828

RESUMO

The WHO recently included Gaming Disorder as a psychiatric diagnosis. Whether there are distinct groups of adolescents who differ based on severity of gaming disorder and their relationships with other mental health and addictive behavior outcomes, including problematic smartphone use (PSU), remains unclear. The current study explored and identified subtypes of Internet Gaming Disorder (IGD) severity and estimated the association between these subtypes and other disorders. Participants completed online questionnaires assessing the severity of IGD, PSU, depression, and anxiety during COVID-19. We conducted a latent class analysis of IGD symptoms among 1,305 Chinese adolescents (mean age = 15.2; male = 58.5%) from 11 secondary schools in Macao (SAR), China. Multinomial logistic regression estimated correlates of latent class membership and PSU. A 4-class model adequately described the sample subgroups. Classes were labeled as normative gamers (30.9%), occasional gamers (42.4%), problematic gamers (22.7%), and addictive gamers (4.1%). Relative to normative gamers, PSU severity, depression, and being male were significantly higher among problematic gamers, addictive gamers, and occasional gamers. Only problematic gamers showed significant positive associations with anxiety severity compared to the other groups. The study revealed the differences in severity of gaming disorder and its association with psychopathology outcomes. Application in screening for IGD and comorbidity is discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03133-8.

9.
Biomed Res Int ; 2022: 4117520, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509713

RESUMO

Osteoarthritis (OA) is one of the age-related diseases and is highly present on the knees. Obesity and mechanical injuries as a risk factor of OA are attributed to cartilage disintegration, joint loading, and inflammation. This study is aimed at investigating the effects of seahorse protein hydrolysate (SH) on posttraumatic osteoarthritis in an obesity rat. The OA model was developed by anterior cruciate ligament transection with medial meniscectomy in a high-fat diet- (HFD-) induced obesity rat model. The male Sprague-Dawley rats were fed a HFD for 6 weeks before OA surgery. The OA rats were treated with oral gavage by 4, 8, or 20 mg/kg of body weight of SH for 6 weeks of treatment. The expressions of plasma proinflammatory factors, C-telopeptide of type II collagen, and matrix metalloproteinase- (MMP-) 3 and MMP-13 were reduced by SH treatment. Plasma superoxide dismutase and glutathione peroxidase activities were enhanced by SH. SH also relieved the pain of the knee joint and swelling as well as decreased proteoglycan loss in the knee articular cartilage caused by osteoarthritis. Based on these results, SH suppressed proinflammatory factors and attenuated cartilage degradation and pain in the OA model. Therefore, seahorse protein hydrolysate might be a potential opportunity for improving the development of osteoarthritis.


Assuntos
Cartilagem Articular , Osteoartrite , Smegmamorpha , Animais , Cartilagem Articular/metabolismo , Modelos Animais de Doenças , Masculino , Obesidade/complicações , Obesidade/metabolismo , Osteoartrite/metabolismo , Dor/metabolismo , Hidrolisados de Proteína/metabolismo , Ratos , Ratos Sprague-Dawley
10.
Artigo em Inglês | MEDLINE | ID: mdl-35579237

RESUMO

Particulate matter poses a serious threat to human health. In particular, exposure to submicron particles can result in more severe health effects as they can deposit more deeply into human tissues. Metal-organic framework (MOF)-based nanofiber filters are regarded as promising candidates for efficient particle control. In this study, ZIF-8@PAN nanofiber filters that were developed via an in situ growth strategy were selected for the filtration of submicron particles. The addition of ZIF-8 more effectively enhanced the filtration of particles with smaller sizes. For the most penetrating particle size of around 0.3 µm, the MOF-based nanofiber filter exhibited an 8.9% increase in filtration efficiency compared with that of the pure nanofiber filter. Meanwhile, for particles with large aerodynamic diameters (in the range of 0.7-1 µm, for example), the role of ZIF-8 was negligible. This work provides important insights into the filtration performance of MOF-based nanofiber filters in capturing submicron particles and may aid in designing nanofiber filters for efficient control of particles.

11.
J Periodontol ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506299

RESUMO

BACKGROUND: Early implant placement with contour augmentation could provide support and volume to the hard and soft tissues. Herein, we aimed to ascertain whether freeze-dried bone allograft (FDBA) shares with deproteinized bovine bone material (DBBM) the results for esthetic outcomes for anterior teeth and stability of peri-implant facial bone thickness and height by conducting guided bone regeneration. METHODS: Forty-eight patients were randomly assigned into two groups. In the control group, autogenous bone chips was used to cover the exposed implant surface, followed by a layer of DBBM. This graft combination was then covered with two layers of collagen membrane. In the test group, the exposed implant surface was covered with FDBA, combined with the collagen membrane. During this study, the hard tissue dimensional changes were measured at 12-months post-implant loading by using cone-beam computed tomography. RESULTS: At 12 months postoperatively, all 48 implants were clinically successful. The mean thickness of facial bone walls ranged from 1.6 to 2.45 mm at the three levels of measurement in the control group and ranged from 1.6 to 2.10 mm in the test group. The mean facial vertical bone wall peak (IP-FC) after loading 1 year presented with values of 0.8 mm (range, 0.0 to 1.25 mm) and 0.5 mm (range, 0.1 to 1.1 mm) coronal to the implant platform in control and test implants, respectively. There were no significant differences in facial bone wall thickness and IP-FC between groups. CONCLUSIONS: This study demonstrated that autogenous bone chips plus DBBM or FDBA showed similar outcome of peri-implant buccal bone stability in early implant placement after 1 year.

12.
Neurospine ; 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35577331

RESUMO

Objective: To analyze differences in feasibility and efficacy between the paravertebral approach and micro-tubular tumorectomy (PAMT) or percutaneous transforaminal endoscopic tumorectomy (PTET) for the treatment of lumbar dumbbell-shaped tumors. Methods: Clinical data of dumbbell-shaped lumbar tumors in patients treated with PAMT or PTET in our hospital between June 2015 and November 2020 were retrospectively analyzed. The gross total resection (GTR) rate, operation time, estimated blood loss, postoperative hospital stay (PHS), postoperative neurological function, and spinal stability were compared between the two surgical methods. Neurological improvement was assessed using the pain visual analog scale (VAS) and the Japanese Orthopaedic Association (JOA) score. Results: Fifteen cases of GTR (93.8%) and one case of subtotal resection were included in the PTET group, whilst all 18 patients in the PAMT group achieved GTR. There was no significant difference in the GTR rate, operation time, and PHS between the PAMT and PTET groups. The estimated blood loss was significantly lower in the PTET group than in the PAMT group. At the last follow-up, there was no significant difference in the VAS or JOA scores between PTET and PAMT. No tumor recurrence or spinal instability was observed in either group during the follow-up period. Conclusion: Both PAMT and PTET can achieve Eden type III-IV lumbar one-stage tumor resection without additional spinal internal fixation due to reduced muscle, ligament, and facet joint damage. No lumbar instability and tumor recurrence occurred, and neurological function was improved.

13.
BMC Health Serv Res ; 22(1): 630, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35545782

RESUMO

BACKGROUND: Facilitating the primary health care (PHC) system and maintaining people's reasonable healthcare-seeking behavior are key to establishing a sustainable healthcare system. China has employed a multitiered copayment system/medical insurance differentiated payment policies to incentivize the public to utilize PHC services through its hierarchical medical care system; however, most people still prefer visiting tertiary care hospitals. We question whether the quality gap in healthcare services reduces the effect of the multitiered copayment system, which is considered an important factor in the lack of reform in the Chinese healthcare system. Thus, we explore the effect and influencing factors of the multitiered copayment system that drives primary healthcare-seeking behavior under the current situation with a large quality gap. We also consider the hypothetical situation of a reduced gap in the future. METHODS: This study used the hypothetical quality improvement scenario to elicit people's hypothetical behaviors, and a multistage stratified cluster random sampling method. This preliminary study was conducted in 2016 using 1829 individuals from four regions of Wenzhou in Zhejiang Province: Ouhai, Ruian, Yongjia, and Taishun. A descriptive statistical analysis, chi-square analysis, Fisher's exact test, and multinomial logistic regression model were performed to introduce the effect of the multitiered copayment system, and to explore the factors affecting the selection of PHC institutions at pre- and post-change phases. RESULT: The results show that compared with the large quality gap phase, the number of respondents who believed the multitiered copayment system had an effect on their selection of PHC institutions after the equalization of healthcare services quality increased threefold (from 14.0% to 50.8%). Moreover, the main determinants in people's selection of PHC institutions changed from age and needs variables (self-rated health status) to age, needs variables (self-rated health status) and enabling variables (distance to a medical care facility). CONCLUSION: The results indicate limited initial effects of the multitiered copayment system. However, they become more pronounced after the equalization of healthcare services quality. This study confirms that changes in the quality gap in healthcare services influence the effect of the multitiered copayment system. Hence, reducing this gap can help achieve the intended outcome of the tiered healthcare insurance schedule.


Assuntos
Atenção à Saúde , Aceitação pelo Paciente de Cuidados de Saúde , China , Nível de Saúde , Humanos
14.
Comput Biol Med ; 146: 105584, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35551013

RESUMO

Atrial fibrillation (AF) is the most common type of sustained arrhythmia. It results from abnormal irregularities in the electrical performance of the atria, and may cause heart thrombosis, stroke, arterial disease, thromboembolism, and heart failure. Prior to the onset of atrial fibrillation, most people experience atrial cardiomyopathy which, if effectively managed, can be prevented from progressing to atrial fibrillation. Electrocardiogram (ECG) can show changes in the heartbeats, and is a common and painless tool to detect heart problems. P-waves in exercise ECGs change more drastically than those in regular ECG, and are more effective in the detection of atrial myocardial diseases. In this paper, we propose a deep learning system to help clinicians to early detect if a patient has atrial enlargement or fibrillation. Firstly, a Convolutional Recurrent Neural Network is employed to locate the P-waves in the patient's exercise ECGs taken in the exercise ECG test process. Relevant parameters are then calculated from the located P-waves. Then a Parallel Bi-directional Long Short-Term Memory Network is applied to analyze the obtained parameters and make a diagnosis for the patient. With our proposed deep learning system, the changes of P-waves collected in different phases in the exercise ECG test can be analyzed simultaneously to get more stable and accurate results. The system can take data of different length as input, and is also applicable to any number of ECG collections. We conduct various experiments to show the effectiveness of our proposed system. We also show that the more ECG data collected in the exercise phase are involved, the more effective our system is in diagnosis of the diseases.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35564659

RESUMO

Advance care planning (ACP) and advance directives (ADs) ensure patient autonomy in end-of life care. The number of ADs made and followed in Taiwan is still lacking. This study aimed to determine the factors that influence the willingness to participate in ACP among outpatients in Taiwan. In this study, we conducted a cross-sectional survey based on convenient sampling methods. The questionnaire included questions about participants' basic sociodemographic information, knowledge of ACP, and awareness of ACP. A total of 198 adults who were outpatients of a family medicine clinic in an affiliated hospital in Taiwan were recruited. The associations between each variable were evaluated using the χ2 test. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression method to examine the influence of each variable on willingness to participate in ACP. Being happy and being a healthcare professional were positively correlated with ACP participation. A lack of ACP knowledge (OR = 0.30 in model A and OR = 0.42 in model C), valuing "Reducing families' end-of-life decision-making burden" (OR = 2.53 in model B and OR = 2.65 in model C), and a "Belief in a good death" (OR = 4.02 in model B and OR = 4.10 in Model C) were the main factors affecting subjects' willingness to participate in ACP. Knowing which factors influence willingness to participate in ACP helps in the promotion of ACP. Continuously educating both the general public and healthcare professionals strengthens knowledge about the right to autonomy, about its associated laws, and about the ACP process, and thus, programs should be created to provide this education. Additionally, taking into account the differences between cultures can be helpful.

16.
Artigo em Inglês | MEDLINE | ID: mdl-35564892

RESUMO

Family members of hazardous or harmful alcohol drinkers suffer many consequences of their relative's alcohol-drinking behaviors and risk developing their own hazardous alcohol drinking behaviors. Studies of alcohol-related healthcare problems have mainly focused on patients, with few studies on their family members. This cross-sectional study explored factors predicting hazardous alcohol drinking behaviors in family members of hazardous alcohol-drinker patients. Participants were recruited from four randomly chosen hospitals in Taiwan. Data were collected using self-report questionnaires on family members' alcohol use, perceived stress, coping mechanisms, social support, health, quality of life, protective factors against hazardous alcohol drinking, facilitative factors for hazardous alcohol drinking, and demographics. The 318 family members who participated in this study were divided by their Chinese-version Alcohol Use Disorders Identification Test scores into two groups: hazardous alcohol drinkers (score ≥ 8) and non-hazardous alcohol drinkers (score < 8). Significant factors predicting hazardous alcohol drinking behaviors were found by logistic regression to be the frequency of using general coping mechanisms (OR = 1.29, p < 0.01), the frequency of using strategies to cope with patients' drinking-related behaviors (OR = 0.89, p < 0.01), factors protecting against hazardous alcohol drinking (OR = 0.76, p < 0.01) and factors facilitating hazardous alcohol drinking (OR = 1.52, p < 0.01). Interventions should be designed for family members of hazardous alcohol drinkers to address these four significant predictors.

17.
Int J Biol Macromol ; 209(Pt B): 1784-1791, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35504416

RESUMO

The biosynthesis of brasilane-type sesquiterpenoids (BTSs) attracts much attention owing to their unique skeleton of 5/6 bicyclic structure that contains five Me groups. Here, the crystal structures of a BTS cyclase TaTC6 from Trichoderma atroviride FKI-3849 and its complexes with farnesyl pyrophosphate (FPP) and analogue were reported. These structural information reveal that TaTC6 exploits a hydrophobic pocket to constrain the hydrocarbon region of FPP in a "U-shape" to facilitate the initial C1-C11 bond formation after pyrophosphate ionization. Following, four carbocations of reaction intermediates were molecularly docked into the hydrophobic pocket to reveal critical residues involved in the cyclization cascade. Finally, an S239-stabilized water molecule that is 3.9 Å away from the C8 of the last allyl cation may conduct hydration to quench the reaction cascade. Mutating S239 to alanine led to ca. 40% reduction in activity compared with the wild-type enzyme. The conservation of the residues that constitute the hydrophobic pocket is also discussed. Overall, this study will give an insight into the mechanism of how the active site of STCs constrain the conformation of the flexible FPP and series allylic carbocations for the complicated-ring formation and unusual carbon rearrangement in the biosynthesis of BTSs.

18.
Front Med (Lausanne) ; 9: 869818, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547225

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to have originated in Wuhan City, Hubei Province, China, in December 2019. Infection with this highly dangerous human-infecting coronavirus via inhalation of respiratory droplets from SARS-CoV-2 carriers results in coronavirus disease 2019 (COVID-19), which features clinical symptoms such as fever, dry cough, shortness of breath, and life-threatening pneumonia. Several COVID-19 waves arose in Taiwan from January 2020 to March 2021, with the largest outbreak ever having a high case fatality rate (CFR) (5.95%) between May and June 2021. In this study, we identified five 20I (alpha, V1)/B.1.1.7/GR SARS-CoV-2 (KMUH-3 to 7) lineage viruses from COVID-19 patients in this largest COVID-19 outbreak. Sequence placement analysis using the existing SARS-CoV-2 phylogenetic tree revealed that KMUH-3 originated from Japan and that KMUH-4 to KMUH-7 possibly originated via local transmission. Spike mutations M1237I and D614G were identified in KMUH-4 to KMUH-7 as well as in 43 other alpha/B.1.1.7 sequences of 48 alpha/B.1.1.7 sequences deposited in GISAID derived from clinical samples collected in Taiwan between 20 April and July. However, M1237I mutation was not observed in the other 12 alpha/B.1.1.7 sequences collected between 26 December 2020, and 12 April 2021. We conclude that the largest COVID-19 outbreak in Taiwan between May and June 2021 was initially caused by the alpha/B.1.1.7 variant harboring spike D614G + M1237I mutations, which was introduced to Taiwan by China Airlines cargo crew members. To our knowledge, this is the first documented COVID-19 outbreak caused by alpha/B.1.1.7 variant harboring spike M1237I mutation thus far. The largest COVID-19 outbreak in Taiwan resulted in 13,795 cases and 820 deaths, with a high CFR, at 5.95%, accounting for 80.90% of all cases and 96.47% of all deaths during the first 2 years. The high CFR caused by SARS-CoV-2 alpha variants in Taiwan can be attributable to comorbidities and low herd immunity. We also suggest that timely SARS-CoV-2 isolation and/or sequencing are of importance in real-time epidemiological investigations and in epidemic prevention. The impact of G614G + M1237I mutations in the spike gene on the SARS-CoV-2 virus spreading as well as on high CFR remains to be elucidated.

19.
Front Pediatr ; 10: 846410, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547546

RESUMO

Background: Out-of-hospital cardiac arrest (OHCA) in children is a critical condition with a poor prognosis. After the coronavirus disease 2019 (COVID-19) pandemic developed, the epidemiology and clinical characteristics of the pediatric emergency department (PED) visits have changed. This study aimed to analyze the impact of the COVID-19 pandemic on pediatric OHCA in the PED. Methods: From January 2018 to September 2021, we retrospectively collected data of children (18 years or younger) with a definite diagnosis of OHCA admitted to the PED. Patient data studied included demographics, pre-/in-hospital information, treatment modalities; and outcomes of interest included sustained return of spontaneous circulation (SROSC) and survival to hospital-discharge (STHD). These were analyzed and compared between the periods before and after the COVID-19 pandemic. Results: A total of 97 patients with OHCA (68 boys and 29 girls) sent to the PED were enrolled in our study. Sixty cases (61.9%) occurred in the pre-pandemic period and 37 during the pandemic. The most common age group was infants (40.2%) (p = 0.018). Asystole was the most predominant cardiac rhythm (72.2%, P = 0.048). Eighty patients (82.5%) were transferred by the emergency medical services, 62 (63.9%) gained SROSC, and 25 (25.8%) were STHD. During the COVID-19 pandemic, children with non-trauma OHCA had significantly shorter survival duration and prolonged EMS scene intervals (both p < 0.05). Conclusion: During the COVID-19 pandemic, children with OHCA had a significantly lower rate of SROSC and STHD than that in the pre-pandemic period. The COVID-19 pandemic has changed the nature of PED visits and has affected factors related to ROSC and STHD in pediatric OHCA.

20.
Thorac Cancer ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35545838

RESUMO

BACKGROUND: As an endocytic nanosicle involved in intercellular communication, an exosome can efficiently deliver drugs from one cell to another and deliver therapeutic short interfering RNA (siRNA) to target cells. This is conducive to gene therapy for cancers. In this study, an exosome was used as the siRNA-loaded substrate to prepare a targeted siRNA-loaded PD-L1 exosome and evaluate its function against lung cancer. METHODS: The optimal preparation process and binding ratio of the targeted nanovesicle/siRNA complex was determined by detecting the particle size, potential, and other physical parameters in combination with cell binding and uptake capacity of exosome complexes. The biological cell behavior of targeted exosome nanosicles was evaluated through cytotoxicity, apoptosis, and the cell uptake capacity. RESULTS: A targeted exosome nanovesicle capable of loading siRNA and characterized with low toxicity, high loading rate, and the ability to be used for targeted tumor cell gene therapy was constructed. CONCLUSION: The PD-L1 targeting exosome can be used as an efficient siRNA delivery carrier, which is an efficient and safe nanocarrier for tumor targeted gene therapy.

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