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1.
J Environ Manage ; 331: 117262, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36731334

RESUMO

Commercial vehicles are important within the context of global warming, since they exhibit greenhouse gas (GHG) emissions that are disproportionate to their quantity. The aim of this study was to create a bottom-up GHG emissions assessment model which considers GHG emissions of newly produced commercial vehicles and those in current use. Through this study, the number of future commercial vehicles were predicted, thereby facilitating a simulation of future GHG emissions. Our results show that the total GHG emissions of commercial vehicles in 2019 was 580 million t CO2-eq.. Among them, the GHG emissions stemming from the production of new commercial vehicles accounted for ∼0.3% of the emissions, whereas the use stage accounted for more than 99.0%. Moreover, the future ownership of commercial vehicles depends on GDP and the demand of freight and passenger transport. The ownership of commercial vehicles was predicted about 36.61 million in 2025, 45.44 million in 2030 and 55.85 million in 2035. The carbon peak of commercial vehicles varies across different scenarios, peaking around 2031-2034, at 680-780 million t CO2-eq.. This study systematically simulated the carbon peak of commercial vehicles, contributing toward a deeper understanding of commercial vehicles within the context of GHG emissions. These results can be applied toward creating quantitatively-driven pathways for carbon peak or neutrality targets in the commercial vehicle sector.

2.
Chem Commun (Camb) ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36722983

RESUMO

Density is an important property of energetic materials and is believed to increase with the addition of heavy trinitromethyl groups, as shown in previous literature. However, this study determined that the introduction of these groups produced a decrease in density, as evidenced by the lower density of 1-trinitromethyl-4-amino-3,5-dinitropyrazole ((TN-116), 1.899 g cm-3) compared to that of its precursor (4-amino-3,5-dinitropyrazole (LLM-116), 1.900 g cm-3). Mechanistic studies indicated that the reduced density was due to the significantly weaker H-bonding and π-π interactions of TN-116, which produced looser stacking compared to that of LLM-116.

3.
J Hazard Mater ; 447: 130815, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36669412

RESUMO

Linoleic acid (LA) shows great potential in inhibiting the growth of multiple red tide microalgae by disturbing algal physio-biochemical processes. However, our knowledge on the mechanisms of algal mortality at metabolic level remains limited. Herein, the response of K. mikimotoi to LA was evaluated using metabolomics, stable isotope techniques (SIT), and physiological indicators. Results showed that 100 µg/L LA promoted the growth of K. mikimotoi, which was significantly inhibited by 500 µg/L LA, along with a significant reduction of photosynthetic pigments and a significant increase of reactive oxygen species (ROS). SIT showed that LA entered algal cells, and 56 isotopologues involved in ferroptosis, carotenoid biosynthesis, and porphyrin metabolism were identified. Non-targeted metabolomics identified 90 and 111 differential metabolites (DEMs) belonging to 11 metabolic pathways under the 500 µg/L and 100 µg/L LA exposure, respectively. Among them, 34 DEMs were detected by SIT. Metabolic pathway analysis showed that 500 µg/L LA significantly promoted ferroptosis, and significantly inhibited carotenoid biosynthesis, porphyrin metabolism, sphingolipid metabolism, and lipopolysaccharide biosynthesis, presenting changes opposite to those observed in 100 µg/L LA-treated K. mikimotoi. Overall, this study revealed the metabolic response of K. mikimotoi to LA, enriching our understanding on the allelochemical mechanism of LA on K. mikimotoi.

4.
Cell Death Dis ; 14(1): 51, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681687

RESUMO

Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Chemoresistance leads to poor responses to conventional therapy in patients with osteosarcoma. The discovery of novel effective therapeutic targets and drugs is still the main focus of osteosarcoma research. Nuclear receptors (NRs) have shown substantial promise as novel therapeutic targets for various cancers. In the present study, we performed a drug screen using 29 chemicals that specifically target 17 NRs in several different human osteosarcoma and osteoblast cell lines. The retinoic acid receptor beta (RARb) antagonist LE135, peroxisome proliferator activated receptor gamma (PPARg) antagonist T0070907, liver X receptor (LXR) agonist T0901317 and Rev-Erba agonist SR9011 significantly inhibited the proliferation of malignant osteosarcoma cells (U2OS, HOS-MNNG and Saos-2 cells) but did not inhibit the growth of normal osteoblasts. The effects of these NR modulators on osteosarcoma cells occurred in a dose-dependent manner and were not observed in NR-knockout osteosarcoma cells. These NR modulators also significantly inhibited osteosarcoma growth in vivo and enhanced the antitumour effect of doxorubicin (DOX). Transcriptomic and immunoblotting results showed that these NR modulators may inhibit the growth of osteosarcoma cells by regulating the PI3K/AKT/mTOR and ERK/mTOR pathways. DDIT4, which blocks mTOR activation, was identified as one of the common downstream target genes of these NRs. DDIT4 knockout significantly attenuated the inhibitory effects of these NR modulators on osteosarcoma cell growth. Together, our results revealed that modulators of RARb, PPARg, LXRs and Rev-Erba inhibit osteosarcoma growth both in vitro and in vivo through the mTOR signaling pathway, suggesting that treatment with these NR modulators is a novel potential therapeutic strategy.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Adolescente , Criança , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , PPAR gama , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Osteossarcoma/metabolismo , Proliferação de Células/genética , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Apoptose
5.
Chemosphere ; 317: 137773, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36621690

RESUMO

Harmful algal blooms (HABs) have frequently occurred worldwide, causing marine ecosystems and human health risks. As an advanced and green oxidation technology, photocatalysis has potential to remove red tide algae using solar energy. Herein, in this work, Z-scheme photocatalysts of Ag3PO4/g-C3N4 (APCN) floating foam with different mass ratios were fabricated for the algae inactivation. Under visible light irradiation, the 0.10APCN (0.10 mM AgNO3) composite photocatalyst could cause 91.8% of the loss in Karenia mikimotoi (K. mikimotoi) cell viability following 24 h and the removal rate of algae could reach to 86% after five successive cycles. The underlying mechanism of photocatalytic inactivation of harmful algae is proposed in this system. The photosynthetic efficiency of harmful algae is inhibited with the decrease of photosynthetic pigments, which are inactivated by the high levels of reactive oxygen species (ROS) (superoxide radical •O2- and hydroxyl radical •OH) produced in Z-scheme photocatalytic system of the Ag3PO4/g-C3N4 heterojunction under visible light. Meanwhile, the activities of antioxidant enzymes (i.e. POD, APX and SOD) are up-regulating with the overproduction of ROS going into the algae, causing the cytotoxicity and apoptosis of algae. This work not only reveals the mechanisms of photocatalytic inactivation of harmful algae, but also guides the design the construction of high active composite photocatalysts, and thus provides theoretical and practical significance for highly efficient and recyclable prospect of controlling of harmful algae.

6.
Adipocyte ; 12(1): 1-10, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36710425

RESUMO

Preadipocytes become mature adipocytes after proliferation and differentiation, and although many genes and microRNAs have been identified in intramuscular fat, their physiological function and regulatory mechanisms remain largely unexplored. miR-26a-5p has been reported to be related to fat deposition, but its effect on porcine preadipocyte differentiation has not been explored. In this study, bioinformatics analysis and luciferase reporter assay identified that miR-26a-5p binds to the 3'UTR of Acyl-CoA synthetase long-chain family member 3 (ACSL3) mRNA. The model for porcine intramuscular preadipocyte differentiation was established to explore the function of miR-6a-5p-ACSL3 on adipocyte differentiation. ACSL3 knockdown markedly reduced the triglycerides (TG) content of cells, as well as the mRNA levels of adipogenic marker genes (PPAR-γ and SREBP-1c). The number of lipid droplets in cells transfected with a miR-26a-5p mimic is significantly reduced, consistent with ACSL3 knockdown results, while the miR-26a-5p inhibitor resulted in opposite results. Taken together, miR-26a-5p is a repressor of porcine preadipocyte differentiation and plays a vital role in ACSL3-mediated adipogenesis.


Assuntos
Adipócitos , MicroRNAs , Animais , Suínos , Adipócitos/metabolismo , Diferenciação Celular/genética , Adipogenia/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo
7.
Future Med Chem ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36651264

RESUMO

Aim: The clinical benefits of FLT3 inhibitors against acute myeloid leukemia (AML) have been limited by selectivity and resistance mutations. Thus, to identify FLT3 inhibitors possessing high selectivity and potency is of necessity. Methods & results: The authors used computational methods to systematically compare pocket similarity with 269 kinases. Subsequently, based on these investigations and beginning with in-house compound 10, they synthesized a series of 6-methyl-isoxazol[3,4-b]pyridine-3-amino derivatives and identified that compound 45 (IC50: 103 nM) displayed gratifying potency in human AML cell lines with FLT3-internal tandem duplications mutation as well as FLT3-internal tandem duplications-tyrosine kinase domain-transformed BaF3 cells. Conclusion: The integrated biological activity results indicated that compound 45 deserves further development for therapeutic remedies for AML.

8.
Drug Dev Res ; 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36644989

RESUMO

Small molecule covalent drugs have proved to be desirable therapies especially on drug resistance related to point mutations. Secondary mutations of FLT3 have become the main mechanism of FLT3 inhibitors resistance which further causes the failure of treatment. Herein, a series of 4-(4-aminophenyl)-6-phenylisoxazolo[3,4-b]pyridine-3-amine covalent derivatives were synthesized and optimized to overcome the common secondary resistance mutations of FLT3. Among these derivatives, compound F15 displayed potent inhibition activities against FLT3 (IC50 = 123 nM) and FLT3-internal tandem duplication (ITD) by 80% and 26.06%, respectively, at the concentration of 1 µM. Besides, F15 exhibited potent activity against FLT3-dependent human acute myeloid leukemia (AML) cell lines MOLM-13 (IC50 = 253 nM) and MV4-11 (IC50 = 91 nM), as well as BaF3 cells with variety of secondary mutations. Furthermore, cellular mechanism assays indicated that F15 inhibited phosphorylation of FLT3 and its downstream signaling factors. Notably, F15 could be considered for further development as potential drug candidate to treat AML.

9.
Chemosphere ; 316: 137793, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36640977

RESUMO

Macrolides have been frequently detected in the surface waters worldwide, posing a threat to the aquatic microbes. Several studies have evaluated the ecotoxicological effects of macrolides on single algal and bacterial strains. However, without considering the species interaction in the aquatic microbial community, these results cannot be extrapolated to the field. Thus, the present study aimed to evaluate the effects of two macrolides (erythromycin and roxithromycin) on the structure, photosynthetic process, carbon utilization capacity, and the antibiotic metabolic pathways in river periphyton. The colonized periphyton was exposed to the graded concentration (0 µg/L (control), 0.5 µg/L (low), 5 µg/L (medium), 50 µg/L (high)) of ERY and ROX, respectively, for 7 days. Herein, high levels of ERY and ROX altered the community composition by reducing the relative abundance of Chlorophyta in the eukaryotic community. Also, the Shannon and Simpson diversity indexes of prokaryotes were reduced, although similar effects were seldomly detected in the low and medium groups. In contrast to the unchanged carbon utilization capacity, the PSII reaction center involved in the periphytic photosynthesis was significantly inhibited by macrolides at high levels. In addition, both antibiotics had been degraded by periphyton, with the removal rate of 51.63-66.87% and 41.85-48.27% for ERY and ROX, respectively, wherein the side chain and ring cleavage were the main degradation pathways. Overall, this study provides an insight into the structural and functional toxicity and degradation processes of macrolides in river periphyton.


Assuntos
Perifíton , Roxitromicina , Eritromicina/toxicidade , Roxitromicina/toxicidade , Roxitromicina/química , Rios , Antibacterianos/toxicidade , Antibacterianos/química , Macrolídeos/toxicidade , Fotossíntese , Carbono/farmacologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-36595184

RESUMO

Residents play a pivotal role in the healthcare system. However, few tools have systematically revealed the dilemmas and challenges faced by residents. This study aimed to develop a checklist for professionalism dilemmas based on a behavior-based professionalism framework and to examine the range and proportion of professionalism dilemmas heard of, witnessed, or experienced by Chinese residents. Mixed methods were used, comprising qualitative (document analysis and focus group interviews) and quantitative (a small-scale questionnaire survey) data. Document analysis summarized professionalism dilemma items from previous publications. For focus group interviews, we used narrative inquiry to explore and make sense of residents' experiences and perceptions of professionalism dilemmas. A small-scale questionnaire survey was conducted during each focus group to investigate the proportion of professionalism dilemma items that residents reported to have heard of, witnessed, or experienced. Through document analysis and focus group interviews, we developed a checklist of professionalism dilemmas based on a behavior-based professionalism framework. The checklist included 58 items over four domains, with 10 sub-domains (compassion, respect, communication, collaboration, integrity, duty, pursuit of excellence, fair stewardship of health care resources, patient confidentiality, and informed consent). We also sought a preliminarily subjective impression by exploring the proportion of residents who have heard of, witnessed, and experienced each of the professionalism dilemma items and residents' perspectives when faced with professionalism dilemmas. Residents inevitably encounter or experience a diverse range of professionalism dilemmas. This checklist of professionalism dilemmas that was developed could prove to be a significant reference for targeted professionalism education, both for the resident as well as for faculty. It can also act as a helpful tool for improving hospital management guidelines and patient education.

11.
ACS Appl Mater Interfaces ; 15(1): 452-468, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36538368

RESUMO

Pyroptosis, as a novel mode of cell death, has been proven to have impressive antitumor effects. Dying cells undergoing pyroptosis can elicit antitumor immunity by the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). Accordingly, developing an effective, stable, and controllable nanoplatform that can promote these two side effects is a promising option for cancer therapy. In this study, we designed a carrier-free chemo-photodynamic nanoplatform (A-C/NPs) using a co-assembly strategy with cytarabine (Ara-C) and chlorin e6 (Ce6) to induce pyroptosis and a subsequent immune response against breast cancer. Mechanistically, A-C/NPs can trigger GSDME-mediated pyroptosis in a controllable manner through reactive oxygen species (ROS) accumulation, causing immunogenic cell death (ICD), in which dying cells release high-mobility group box 1 (HMGB1), adenosine triphosphate (ATP), and calcitonin (CRT). Additionally, Ara-C can stimulate the maturation of cytotoxic T lymphocytes to act synergistically with Ce6-mediated immunogenic cell death (ICD), collectively augmenting the anticancer effect of A-C/NPs. The A-C/NPs showed excellent suppressive effects on the growth of orthotopic, abscopal, and recurrent tumors in a breast cancer mouse model. The chemo-photodynamic therapy (PDT) using the proposed nanomedicine strategy could be a novel strategy for triggering pyroptosis and improving the global anticancer immune response.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Piroptose , Citarabina , Imunidade , Linhagem Celular Tumoral
12.
Mol Psychiatry ; 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36460727

RESUMO

Histidine phosphorylation (pHis), occurring on the histidine of substrate proteins, is a hidden phosphoproteome that is poorly characterized in mammals. LHPP (phospholysine phosphohistidine inorganic pyrophosphate phosphatase) is one of the histidine phosphatases and its encoding gene was recently identified as a susceptibility gene for major depressive disorder (MDD). However, little is known about how LHPP or pHis contributes to depression. Here, by using integrative approaches of genetics, behavior and electrophysiology, we observed that LHPP in the medial prefrontal cortex (mPFC) was essential in preventing stress-induced depression-like behaviors. While genetic deletion of LHPP per se failed to affect the mice's depression-like behaviors, it markedly augmented the behaviors upon chronic social defeat stress (CSDS). This augmentation could be recapitulated by the local deletion of LHPP in mPFC. By contrast, overexpressing LHPP in mPFC increased the mice's resilience against CSDS, suggesting a critical role of mPFC LHPP in stress-induced depression. We further found that LHPP deficiency increased the levels of histidine kinases (NME1/2) and global pHis in the cortex, and decreased glutamatergic transmission in mPFC upon CSDS. NME1/2 served as substrates of LHPP, with the Aspartic acid 17 (D17), Threonine 54 (T54), or D214 residue within LHPP being critical for its phosphatase activity. Finally, reintroducing LHPP, but not LHPP phosphatase-dead mutants, into the mPFC of LHPP-deficient mice reversed their behavioral and synaptic deficits upon CSDS. Together, these results demonstrate a critical role of LHPP in regulating stress-related depression and provide novel insight into the pathogenesis of MDD.

13.
Front Oncol ; 12: 1039888, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465366

RESUMO

Background: The role of consolidation therapy with autologous stem cell transplantation (ASCT) in patients with peripheral T-cell lymphoma (PTCL) in first complete remission (CR1) or partial remission (PR1) remains controversial. The existing data from China are limited. Therefore, we aimed to investigate the effect of ASCT on the survival of Chinese patients with PTCL showing response to induction chemotherapy at our hospital. Methods: We retrospectively reviewed the data of patients with PTCL (excluding Natural killer/T cell lymphoma) in CR1 or PR1 treated at Peking University Hospital &Institute from 1996 to 2020. Propensity score matching (PSM) was used to balance clinical characteristics between the ASCT and non-ASCT groups. The primary endpoints were event-free survival (EFS) and overall survival (OS). Results: Of the 414 selected patients, 73 received ASCT consolidation and 341 did not. Over a median follow-up of 5.7 years, survival was significantly better in the ASCT group than in the non-ASCT group (median EFS, 8.1 years vs. 2.8 years, P = 0.002; median OS, 14.9 years vs. 10.2 years, P = 0.007). The 5-year EFS and OS rates were 68.4% and 77.0% in ASCT group, and 43.2% and 57.6% in non-ASCT group, respectively. The survival benefit was confirmed in the propensity score matched cohort (46 patients who received ASCT and 84 patients who did not receive ASCT): P = 0.007 for median EFS and P = 0.022 for the median OS. Cox regression analysis showed that ASCT was independently associated with better survival: hazard ratio (HR) for EFS, 0.46 (95% CI: 0.28-0.76); HR for OS, 0.50 (95% CI: 0.31-0.84). Subgroup analysis showed that ASCT was more likely to benefit higher-risk patients and those with advanced disease. Among the subtypes of PTCL, the benefit was significant in angioimmunoblastic T-cell lymphoma (HR = 0.26 [95% CI: 0.10-0.66] for EFS and 0.29 [95% CI: 0.12-0.74] for OS), but not in the other subtypes. Conclusion: ASCT may improve the long-term survival of patients with PTCL in first CR or PR, especially for patients with angioimmunoblastic T-cell lymphoma. The specific groups most likely to benefit from upfront ASCT need to be clearly identified.

14.
J Clin Pharm Ther ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36452989

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The management of biological agents during pregnancy poses challenges as maternal and infant safety must be addressed. This study aims to compare the recommendations of existing guidelines on managing the use of biologics during pregnancy, lactation for patients with inflammatory bowel disease, and the influence on neonatal vaccination. METHODS: The PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database and China Biomedical Database were systematically searched from the inception date to 11 May 2022, to screen all relevant guidelines. Quality assessment was performed using the guideline methodology reporting tool AGREE II. RESULTS AND DISCUSSION: Fourteen guidelines and consensus statements with detailed recommendations were included. All guidance documents cover management comments during pregnancy, and most consider that biologics can be given safely during pregnancy but require suspension at the right time to protect the foetus. However, the roles of vedolizumab and ustekinumab are disputed. Five documents guide lactation and the use of most biologics during lactation is safe, but no guidelines recommend vedolizumab. Six papers provide recommendations for newborns' vaccination, suggesting a delay in infants' live vaccination schedule if their mothers are treated with biologics. WHAT IS NEW AND CONCLUSION: Our study concluded that future guidelines could consider incorporating newer, more robust evidence to update recommendations. The development of future guidelines needs to consider the involvement of multidisciplinary experts, adequately report on the evidence retrieval process, and provide strategies for implementation. Besides, more research is needed to explore the use of biologics during pregnancy and lactation in patients with inflammatory bowel disease.

15.
Nucleic Acids Res ; 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36453990

RESUMO

Chromatin remodelers have been thought to be crucial in creating an accessible chromatin environment before transcription activation. However, it is still unclear how chromatin remodelers recognize and bind to the active regions. In this study, we found that chromatin remodelers SPLAYED (SYD) and BRAHMA (BRM) interact and co-occupy with Suppressor of Ty6-like (SPT6L), a core subunit of the transcription machinery, at thousands of the transcription start sites (TSS). The association of SYD and BRM to chromatin is dramatically reduced in spt6l and can be restored mainly by SPT6LΔtSH2, which binds to TSS in a RNA polymerase II (Pol II)-independent manner. Furthermore, SPT6L and SYD/BRM are involved in regulating the nucleosome and Pol II occupancy around TSS. The presence of SPT6L is sufficient to restore the association of the chromatin remodeler SYD to chromatin and maintain normal nucleosome occupancy. Our findings suggest that the two chromatin remodelers can form protein complexes with the core subunit of the transcription machinery and regulate nucleosome occupancy in the early transcription stage.

16.
Front Public Health ; 10: 1011801, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36544803

RESUMO

Background: Academic procrastination has become more prevalent during the COVID-19 pandemic due to teaching/learning changes. This phenomenon induces academic burnout, which is already serious among medical students. However, the academic emotion, which is the factor most vulnerable to changes in the academic environment, is still unknown. Therefore, the current study aimed to investigate the mediating role of general academic emotions in procrastination and burnout among Chinese medical students during the COVID-19 pandemic. Methods: This cross-sectional study enrolled 995 medical students from China Medical University. We applied the Chinese version of the Maslach Burnout Inventory Student Survey (MBI-SS), the Aitken Procrastination Inventory (API) and the General Academic Emotion Questionnaire for College Students (GAEQ) to evaluate the variables of interest. We examined the mediation effects of GAEs by hierarchical linear regression analysis. Results: Correlation analyses showed a significant positive correlation between procrastination and burnout. Procrastination and burnout positively and negatively correlated with negative academic emotions, respectively. Hierarchical linear regression analyses showed that procrastination had positive associations with negative academic emotions, while it had negative associations with positive academic emotions. The contributions (as mediators) of GAEs to burnout and procrastination were 21.16% (NAEs), 29.75% (PAEs), 54.25% (NDEs) and 23.69% (PDEs). Conclusions: The results indicate that academic emotions had mediating effects on procrastination and burnout. Medical students' worries about the uncertainty of the learning environment may have exacerbated academic burnout. Targeted improvements in the teaching environment to communicate encouragement and reduce anxiety and helplessness among medical undergraduates for implementing medical education while preventing and controlling the infection.


Assuntos
Esgotamento Profissional , COVID-19 , Procrastinação , Estudantes de Medicina , Humanos , Estudos Transversais , Pandemias , COVID-19/epidemiologia , Emoções , Esgotamento Psicológico , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Estudantes de Medicina/psicologia
17.
Front Microbiol ; 13: 1044986, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36504773

RESUMO

Black soldier fly (Hermetia illucens) larvae (BSFL) act as a biological system converting organic waste into protein and fat with great potential application as pet food. To evaluate the feasibility of BSFL as a protein and fat source, 20 healthy beagle dogs were fed three dietary treatments for 65 days, including (1) a basal diet group (CON group), (2) a basal diet that replaced 20% chicken meal with defatted black soldier fly larvae protein group (DBP group), and (3) a basal diet that replaced 8% mixed oil with black soldier fly larvae fat group (BF group). This study demonstrated that the serum biochemical parameters among the three groups were within the normal range. No difference (p > 0.05) was observed in body weight, body condition score, or antioxidant capacity among the three groups. The mean IFN-γ level in the BF group was lower than that in the CON group, but there was no significant difference (p > 0.05). Compared with the CON group, the DBP group had decreasing (p < 0.05) apparent crude protein and organic matter digestibility. Furthermore, the DBP group had decreasing (p < 0.05) fecal propionate, butyrate, total short-chain fatty acids (SCFAs), isobutyrate, isovalerate, and total branched-chain fatty acids (BCFAs) and increased (p < 0.05) fecal pH. Nevertheless, there was no difference (p > 0.05) in SCFAs or BCFAs between the CON and BF groups. The fecal microbiota revealed that Lachnoclostridium, Clostridioides, Blautia, and Enterococcus were significantly enriched in the DBP group, and Terrisporobacter and Ralstonia were significantly enriched in the BF group. The fecal metabolome showed that the DBP group significantly influenced 18 metabolic pathways. Integrating biological and statistical correlation analysis on differential fecal microbiota and metabolites between the CON and DBP groups found that Lachnoclostridium, Clostridioides, and Enterococcus were positively associated with biotin. In addition, Lachnoclostridium, Clostridioides, Blautia, and Enterococcus were positively associated with niacinamide, phenylalanine acid, fumaric acid, and citrulline and negatively associated with cadavrine, putrescine, saccharopine, and butyrate. In all, 20% DBP restrained the apparent CP and OM digestibility, thereby affecting hindgut microbial metabolism. In contrast, 8% BF in the dog diet showed no adverse effects on body condition, apparent nutrient digestibility, fecal microbiota, or metabolic profiles. Our findings are conducive to opening a new avenue for the exploitation of DBP and BF as protein and fat resources in dog food.

18.
Cancers (Basel) ; 14(24)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36551506

RESUMO

ESCC is a highly malignant tumor, and its morbidity and mortality in China account for more than 50% of the world's total rates. As effective treatments are lacking, the 5-year survival rate of patients does not exceed 30%. CAR-T-cell-based immunotherapy has emerged as one of the most promising cancer treatments; however, there are relatively fewer reports regarding its application for ESCC. In this study, we conducted large-sample whole-genome sequencing (WGS) and RNA-seq analysis of patients with ESCC from China to examine the feasibility of EGFR-targeting CAR-T cells in the treatment of ESCC. We found much higher levels of EGFR gene amplification and overexpression in tumors than in the normal tissues, indicating that EGFR could be a promising target of CAR-T-cell-based immunotherapy in ESCC. Therefore, we tested EGFR-targeting CAR-T cells for lytic activity against ESCC cells as a model to establish cellular immunotherapy for ESCC. Five types of CAR-T cells targeting EGFR were constructed, two of which, CAR1-T and CAR2-T, showed a strong cytotoxicity against ESCC in in vitro and in vivo experiments. The results of this study suggest that CAR1-T and CAR2-T have the potential to be used for anti-ESCC immunotherapy in clinics.

19.
Cancer Control ; 29: 10732748221143881, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36519740

RESUMO

INTRODUCTION: Mantle cell lymphoma (MCL) is an aggressive and incurable B-cell-derived malignant disease. MCL is treated using general chemotherapy; however, disease progression and relapse are common; thus, the development of novel therapeutic targets for treatment of MCL is urgently required. Serum- and glucocorticoid-inducible kinase 1 (SGK1) is involved in various cellular activities, and its dysregulation contributes to the pathogenesis of multiple types of cancer. However, little is known regarding its functional roles and associated molecular mechanisms in MCL. METHODS: SGK1 inhibition mediated by either shRNA or treatment with SGK1 inhibitor (GSK650394) was conducted in MCL cell lines. Western blotting analysis was performed to figure out the expression of related proteins. MCL-cell-derived xenograft models were constructed to evaluate the anti-tumor effects of SGK1 inhibition or/and Bruton's tyrosine kinase (BTK) inhibition in vivo. RESULTS: In this study, it was shown that inhibition of SGK1 significantly reduced cell proliferation, invasion and migration, increased apoptosis and blocked cell cycle progression in MCL cells. Furthermore, SGK1 inhibition significantly reduced the activation of ERK, AKT/mTOR, JAK2/STAT3 and the NF-κB signaling pathways. Using MCL-cell-derived xenograft mice models, SGK1 inhibition decreased tumor cell proliferation and tumor growth. Importantly, SGK1 overexpression significantly promoted xenograft tumor growth. Moreover, simultaneous inhibition of SGK1 and Bruton tyrosine kinase (BTK) resulted in synergistic anti-tumor effects on MCL both in vitro and in vivo. CONCLUSION: SGK1 may be a novel candidate therapeutic target and simultaneous inhibition of SGK1 and BTK may be a promising therapeutic strategy for MCL patients. Further pre-clinical and even clinical studies of SGK1 inhibitor or combination with BTK inhibitor are essential.


Assuntos
Linfoma de Célula do Manto , Humanos , Camundongos , Adulto , Animais , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/patologia , Glucocorticoides/uso terapêutico , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Pirimidinas/uso terapêutico , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Piperidinas/uso terapêutico
20.
Eur J Med Res ; 27(1): 294, 2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36528689

RESUMO

OBJECTIVE: Early identifying sepsis patients who had higher risk of poor prognosis was extremely important. The aim of this study was to develop an artificial neural networks (ANN) model for early predicting clinical outcomes in sepsis. METHODS: This study was a retrospective design. Sepsis patients from the Medical Information Mart for Intensive Care-III (MIMIC-III) database were enrolled. A predictive model for predicting 30-day morality in sepsis was performed based on the ANN approach. RESULTS: A total of 2874 patients with sepsis were included and 30-day mortality was 29.8%. The study population was categorized into the training set (n = 1698) and validation set (n = 1176) based on the ratio of 6:4. 11 variables which showed significant differences between survivor group and nonsurvivor group in training set were selected for constructing the ANN model. In training set, the predictive performance based on the area under the receiver-operating characteristic curve (AUC) were 0.873 for ANN model, 0.720 for logistic regression, 0.629 for APACHEII score and 0.619 for SOFA score. In validation set, the AUCs of ANN, logistic regression, APAHCEII score, and SOFA score were 0.811, 0.752, 0.607, and 0.628, respectively. CONCLUSION: An ANN model for predicting 30-day mortality in sepsis was performed. Our predictive model can be beneficial for early detection of patients with higher risk of poor prognosis.


Assuntos
Unidades de Terapia Intensiva , Sepse , Humanos , Estudos Retrospectivos , Prognóstico , Sepse/diagnóstico , Curva ROC , Cuidados Críticos , Redes Neurais de Computação
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