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1.
Inorg Chem ; 63(35): 16533-16540, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39167756

ABSTRACT

Employing hydrogen-bonded organic frameworks (HOFs) as mild photocatalysts for organic conversions is still considerably challenging. In this work, we synthesized a hydrogen-bonded organic framework (HOF-16) and achieved the photocatalytic oxidation of silanes to generate silanols. Considering the constraints imposed by the framework structure, a significant improvement in the efficacy of singlet oxygen (1O2) generation is observed. HOF-16 exhibits remarkable photocatalytic performance when it comes to silane hydroxylation, displaying high efficiency, low catalyst loading, and good recyclability. This research highlights the immense potential of HOFs in the realm of organic photocatalysis.

2.
Langmuir ; 40(36): 19279-19286, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39207173

ABSTRACT

Supramolecular polymers, with their specific functional units and structures, can effectively enhance the absorption and utilization of light energy, thereby facilitating more efficient photocatalytic organic reactions. In the present work, we constructed a supramolecular polymer consisting of benzothiazole derivatives (BTBP) and cucurbit[8]uril (CB[8]). The BTBP monomer, known for its unique chemical structure and properties, has been found to exhibit a remarkable capability in generating singlet oxygen (1O2). As a result of the constraining impact of the macrocyclic molecule, the inclusion of CB[8] resulted in an effective enhancement in the ability to generate 1O2 while forming supramolecular polymer BTBP-CB[8]. When evaluating the quantum yield of 1O2 using Rose Bengal (RB) as a reference photosensitizer (75% in water), BTBP-CB[8] demonstrated an enhanced 1O2 quantum yield compared to BTBP, with an impressive yield of 152.4%, demonstrating that the formation of supramolecular polymer contributes to its ability to generate 1O2. Subsequently, BTBP-CB[8], a highly efficient 1O2 generator, was employed for the photocatalytic Minisci alkylation reaction, resulting in an impressive reaction yield of up to 89%. The supramolecular polymer strategies employed in the construction of photocatalytic systems have exhibited remarkable efficacy in the production of 1O2, underscoring their immense prospects in photocatalysis.

3.
Front Public Health ; 12: 1321123, 2024.
Article in English | MEDLINE | ID: mdl-38784570

ABSTRACT

Background: Scrub typhus, caused by the Orientia tsutsugamushi (Ot), is a widespread vector-borne disease transmitted by chigger mites. Hemophagocytic lymphohistiocytosis (HLH) is considered to be one of the potentially severe complications. The diagnosis of scrub typhus-associated HLH may be overlooked due to the non-specific clinical characteristics and the absence of pathognomonic eschar. Case presentation: We obtained clinical data from two patients in the South of Sichuan, China. The first case involved a 6-year-old girl who exhibited an unexplained fever and was initially diagnosed with sepsis, HLH, and pulmonary infection. The other patient presented a more severe condition characterized by multiple organ dysfunction and was initially diagnosed with septic shock, sepsis, HLH, acute kidney injury (AKI), and pulmonary infection. At first, a specific examination for scrub typhus was not performed due to the absence of a characteristic eschar. Conventional peripheral blood cultures yielded negative results in both patients, and neither of them responded to routine antibiotics. Fortunately, the causative pathogen Orientia tsutsugamushi (Ot) was detected in the plasma samples of both patients using metagenomics next-generation sequencing (mNGS) and further confirmed by polymerase chain reaction. Subsequently, they both were treated with doxycycline and recovered quickly. Conclusion: The unbiased mNGS provided a clinically actionable diagnosis for an uncommon pathogen-associated infectious disease that had previously evaded conventional diagnostic approaches.


Subject(s)
Lymphohistiocytosis, Hemophagocytic , Orientia tsutsugamushi , Scrub Typhus , Scrub Typhus/diagnosis , Scrub Typhus/complications , Humans , Female , Child , Orientia tsutsugamushi/isolation & purification , Orientia tsutsugamushi/genetics , Lymphohistiocytosis, Hemophagocytic/diagnosis , China , Male , Doxycycline/therapeutic use
4.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1641-1660, 2024 Mar.
Article in Chinese | MEDLINE | ID: mdl-38621949

ABSTRACT

This study explored the existence forms(original constituents and metabolites) of Tiantian Capsules, Aloe, and Tiantian Capsules without Aloe in rats for the first time, aiming to clarify the contribution of Aloe to the existence form of Tiantian Capsules. Rats were administrated with corresponding drugs by gavage once a day for seven consecutive days. All urine and feces samples were collected during the seven days of administration, and blood samples were collected 0.5, 1, and 1.5 h after the last administration. UHPLC-Q-TOF-MS was employed to detect and identify the original constituents and metabolites in the samples. A total of 34, 28, and 2 original constituents and 64, 94, and 0 metabolites were identified in the samples of rats administrated with Aloe, Tiantian Capsules, and Tiantian Capsules without Aloe, respectively. The main metabolic reactions were methylation, hydrogenation, hydroxylation, dehydroxylation, glucuronidation, and sulfation. This study clarified for the first time the existence forms and partial metabolic pathways of Aloe, Tiantian Capsules, and Tiantian Capsules without Aloe in rats, laying a foundation for revealing their effective forms. The findings are of great significance to the research on the functioning mechanism and quality control of Aloe and Tiantian Capsules.


Subject(s)
Aloe , Drugs, Chinese Herbal , Rats , Animals , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/metabolism , Administration, Oral , Feces , Capsules
5.
Cell ; 187(3): 764-781.e14, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38306985

ABSTRACT

Pregnancy induces dramatic metabolic changes in females; yet, the intricacies of this metabolic reprogramming remain poorly understood, especially in primates. Using cynomolgus monkeys, we constructed a comprehensive multi-tissue metabolome atlas, analyzing 273 samples from 23 maternal tissues during pregnancy. We discovered a decline in metabolic coupling between tissues as pregnancy progressed. Core metabolic pathways that were rewired during primate pregnancy included steroidogenesis, fatty acid metabolism, and arachidonic acid metabolism. Our atlas revealed 91 pregnancy-adaptive metabolites changing consistently across 23 tissues, whose roles we verified in human cell models and patient samples. Corticosterone and palmitoyl-carnitine regulated placental maturation and maternal tissue progenitors, respectively, with implications for maternal preeclampsia, diabetes, cardiac hypertrophy, and muscle and liver regeneration. Moreover, we found that corticosterone deficiency induced preeclampsia-like inflammation, indicating the atlas's potential clinical value. Overall, our multi-tissue metabolome atlas serves as a framework for elucidating the role of metabolic regulation in female health during pregnancy.


Subject(s)
Metabolomics , Pregnancy , Animals , Female , Humans , Pregnancy/metabolism , Corticosterone/metabolism , Metabolome/physiology , Placenta/metabolism , Pre-Eclampsia , Primates/metabolism
6.
Anal Chem ; 96(2): 787-793, 2024 01 16.
Article in English | MEDLINE | ID: mdl-38170819

ABSTRACT

In the clinic, small-molecule metabolites (SMMs) in blood are highly convincing indicators for disease diagnosis, such as cancer. However, challenges still exist for detection of SMMs due to their low concentration and complicated components in blood. In this work, we report the design of a novel "selenium signature" nanoprobe (Se nanoprobe) for efficient identification of multiple aldehyde metabolites in blood. This Se nanoprobe consists of magnetic nanoparticles that can enrich aldehyde metabolites from a complex environment, functionalized with photosensitive "selenium signature" hydrazide molecules that can react with aldehyde metabolites. Upon irradiation with UV, the aldehyde derivatives can be released from the Se nanoprobe and further sprayed by mass spectrometry through ambient ionization (AIMS). By quantifying the selenium isotope distribution (MS/MS) from the derivatization product, accurate detection of several aldehyde metabolites, including valeraldehyde (Val), heptaldehyde (Hep), 2-furaldehyde (2-Fur), 10-undecenal aldehyde (10-Und), and benzaldehyde (Ben), is realized. This strategy reveals a new solution for quick and accurate cancer diagnosis in the clinic.


Subject(s)
Neoplasms , Selenium , Humans , Tandem Mass Spectrometry/methods , Aldehydes
7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1028723

ABSTRACT

AIM To establish an HPLC method for the simultaneous content determination of urine,guanosine,adenosine,(R,S)-hysterone,chlorogenic acid,forsythian glycoside A,luteolin,3,5-dicaffeioyl quinic acid,4,5-dicaffeioyl quinic acid and phillyrin in Xiao'er Ganmao Granules.METHODS The analysis was performed on a 40℃thermostatic Welchrom C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2%glacial acetic acid flowing at 0.8,1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 230,254,327 nm.RESULTS Ten constituents showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 93.68%-98.08%with the RSDs of 0.90%-1.86%.CONCLUSION This stable and reliable method can be used for the quality control of Xiao'er Ganmao Granules.

8.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1028745

ABSTRACT

AIM To establish a quantitative analysis of multi-components by single-marker(QAMS)method for the simultaneous content determination of gastrodin,parishin E,syringin,parishin B,parishin C,ferulic acid,parishin A,buddleoside,harpagoside and cinnamic acid in Tianma Toufengling Capsules.METHODS The analysis was performed on a 30℃thermostatic GL Science InertsilTM ODS-3 column(150 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 220,280 nm.Syringin was used as an internal standard to calculate the relative correction factors of the other nine constituents,after which the content determination was made.RESULTS Ten constituents showed good linear relationships within their own ranges(r≥0.999 7),whose average recoveries were 98.53%-102.22%with the RSDs of 1.26%-2.68%.The result obtained by QAMS approximated those obtained by external standard method.CONCLUSION This accurate and specific method can be used for the quality control of Tianma Toufengling Capsules.

9.
Medicine (Baltimore) ; 102(43): e35721, 2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37904382

ABSTRACT

RATIONALE: The rare t(3;21)(q26;q22) translocation results in gene fusion and generates multiple fusion transcripts, which are typically associated with therapy-related myelodysplastic syndrome, acute myeloid leukemia, and chronic myelogenous leukemia. Here, we report a rare case of de novo acute myelomonocytic leukemia in a young child with t(3;21)(q26;q22). PATIENT CONCERNS: A 2-and-a-half-year-old female patient presented with abdominal pain, cough, paleness, and fever for 3 weeks, without any history of malignant diseases. DIAGNOSES: Chest computed tomography revealed pneumonia. Bone marrow smear confirmed acute myelomonocytic leukemia. Cytogenetic analysis and Sanger sequencing identified RUNX1-MECOM and RUNX1-RPL22 fusion genes as a result of t(3;21)(q26;q22). INTERVENTIONS: The patient received 3 courses of chemotherapy, but bone marrow smear examination showed no remission. According to the wishes of the patient family, the allogeneic hematopoietic stem cell transplantation (Allo-HSCT) was chosen. OUTCOMES: The patient did not experience any adverse reactions after Allo-HSCT. The red blood cells and platelets increased without transfusion. The pneumonia recovered after antibiotic treatment. LESSONS: The patient recovered well after Allo-HSCT. Therefore, for patients with RUNX1-MECOM and RUNX1-RPL22 fusion genes, transplantation may be a good choice when chemotherapy is not effective.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Leukemia, Myelomonocytic, Acute , Pneumonia , Female , Humans , Child , Child, Preschool , Core Binding Factor Alpha 2 Subunit/genetics , Leukemia, Myeloid, Acute/genetics , Hematopoietic Stem Cell Transplantation/methods , Translocation, Genetic , Pneumonia/genetics , Chromosomes, Human, Pair 21
10.
Seizure ; 110: 126-135, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37356182

ABSTRACT

The objective of this study is to analyze the role of dehydrodolichyl diphosphate synthase (DHDDS), a crucial enzyme in the mevalonate pathway, and its encoded mutations in the onset of developmental delay and seizures, with or without movement abnormalities. Its genotype-phenotype characteristics are still inconclusive. We analyzed the clinical characteristics of epilepsy, and neurodevelopmental and motor disorders related to DHDDS gene mutations and report the genotype-phenotype characteristics of a child with epilepsy caused by DHDDS gene mutation, providing a summary and a statistical analysis of epilepsy cases associated with DHDDS gene mutation up until February 2022. METHODS: Using "DHDDS; epilepsy; neurodevelopmental disorder" as the keywords, the literature relevant to DHDDS gene mutations up until February 2022 was reviewed. A total of 25 cases were retrieved, among which 21 cases with complete data were included in the chi-squared test. The clinical characteristics of DHDDS gene-related cases were summarized and analyzed. RESULTS: The onset of epilepsy caused by mutations of the DHDDS gene typically occurs during infancy. Predominantly, the mutation occurs in the locus of c.632G>A p.R211Q. Myoclonus is frequently the initial manifestation of epilepsy; it frequently coexists with neurodevelopmental disorder and intellectual disability, and patients have no specific type of motor disorder. Cranial magnetic resonance imaging (MRI) reveals no abnormalities, whereas electroencephalogram (EEG) frequently exhibits abnormalities. Valproic acid (VPA) yields good curative effects. CONCLUSION: Mutations in the DHDDS gene are associated with congenital glycosylation disorder, autosomal recessive retinitis pigmentosa, and epilepsy. According to statistical analysis using the chi-squared test, for pediatric patients with mutations in this gene locus, most of the epilepsy types are myoclonic epilepsies with intellectual disability and neurodevelopmental disorders. They have normal brain MRIs and abnormal EEGs. VPA produces beneficial therapeutic results and the differences are all statistically significant. The current diagnosis still relies on next-generation sequencing or whole-exome sequencing.


Subject(s)
Epilepsy , Intellectual Disability , Motor Disorders , Neurodevelopmental Disorders , Humans , Intellectual Disability/diagnostic imaging , Intellectual Disability/genetics , Mutation/genetics , Neurodevelopmental Disorders/diagnostic imaging , Neurodevelopmental Disorders/genetics , Epilepsy/diagnostic imaging , Epilepsy/drug therapy , Epilepsy/genetics , Phenotype
11.
J Fish Dis ; 46(9): 967-976, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37329523

ABSTRACT

Dactylogyrus is one of the most common parasitic diseases in fish and causes huge losses to the aquaculture industry. With the advantages of safety, low toxicity and easy degradation, plant-derived drugs are ideal for the creation of green aquatic ingredients. The use of plant-derived drugs in aquaculture is limited by their low content and high processing costs, which is a challenge that can be solved by the chemical synthesis of plant-derived drugs. Eleven new coumarin derivatives were synthesized and assessed for their anthelmintic activity in this study. Among them, the derivative 7-((1-tosyl-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (N11) has good anthelmintic activity and its mean anthelmintic efficacy against D. intermedius at a concentration of 10 µM reached 99.84%, which is even better than the anthelmintic activity of the positive control mebendazole. Further studies showed that N11 had concentration values of 3.31 and 1.94 µM for 50% maximal effect (EC50 ) against D. intermedius at 24 and 48 h, respectively. Furthermore, scanning electron microscopy revealed that N11 caused damage to D. intermedius. What is more noteworthy is that a substantial reduction in the ATP content of the parasite was observed following in vitro and in vivo administration of N11. Moreover, it was also found that N11 was able to inhibit the horizontal transmission of D. intermedius. Furthermore, real-time quantitative PCR analysis was utilized to determine the expression profile of genes associated with anti-inflammatory cytokines (IL-10, TGF-ß and IL-4) in goldfish. In all examined organs, it was observed that the expression of anti-inflammatory cytokines increased subsequent to treatment with N11, according to the results. Thus, these results all suggest that N11 possesses good anthelmintic activity and is a potentially effective agent for the control of D. intermedius.


Subject(s)
Anthelmintics , Fish Diseases , Parasites , Trematoda , Animals , Fish Diseases/drug therapy , Fish Diseases/parasitology , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Cytokines , Coumarins/pharmacology , Coumarins/therapeutic use
12.
Cell Res ; 33(9): 712-726, 2023 09.
Article in English | MEDLINE | ID: mdl-37188880

ABSTRACT

During homeostasis and after injury, adult muscle stem cells (MuSCs) activate to mediate muscle regeneration. However, much remains unclear regarding the heterogeneous capacity of MuSCs for self-renewal and regeneration. Here, we show that Lin28a is expressed in embryonic limb bud muscle progenitors, and that a rare reserve subset of Lin28a+Pax7- skeletal MuSCs can respond to injury at adult stage by replenishing the Pax7+ MuSC pool to drive muscle regeneration. Compared with adult Pax7+ MuSCs, Lin28a+ MuSCs displayed enhanced myogenic potency in vitro and in vivo upon transplantation. The epigenome of adult Lin28a+ MuSCs showed resemblance to embryonic muscle progenitors. In addition, RNA-sequencing revealed that Lin28a+ MuSCs co-expressed higher levels of certain embryonic limb bud transcription factors, telomerase components and the p53 inhibitor Mdm4, and lower levels of myogenic differentiation markers compared to adult Pax7+ MuSCs, resulting in enhanced self-renewal and stress-response signatures. Functionally, conditional ablation and induction of Lin28a+ MuSCs in adult mice revealed that these cells are necessary and sufficient for efficient muscle regeneration. Together, our findings connect the embryonic factor Lin28a to adult stem cell self-renewal and juvenile regeneration.


Subject(s)
Adult Stem Cells , Satellite Cells, Skeletal Muscle , Animals , Mice , Muscle, Skeletal , Muscle Fibers, Skeletal , Cell Self Renewal
13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-985505

ABSTRACT

Objective: To explore the risk intensity and related influencing factors of post-traumatic stress disorder (PTSD) among high-stress rescue workers, and to provide effective tools for the risk assessment of PTSD in military rescue workers. Method: From June to August 2022, cluster sampling was used to select the high-stress rescue personnel of an Army department as the survey subjects. The acute Stress reaction (ASD) scale and PTSD checklist were used to evaluate the risk of PTSD in military rescue personnel. Multivariate logistic regression were used to analyze the influencing factors of PTSD. Results: The age of 4 460 subjects was (24.38±4.072) years old, including 4 396 males (98.6%). The positive rate of initial screening for ASD was 2.85% (127/4 460). The positive rate of PTSD was 0.67% (30/4 460). Multivariate logistic regression model analysis showed that female, older age, recent trauma exposure history, passive smoking and alcohol consumption were at higher risk of ASD, the values of OR (95%CI) were 4.183 (1.819-9.618), 6.278 (1.363-28.912), 3.094 (1.500-6.379), 2.059 (1.298-3.267) and 2.607 (1.614-4.211), respectively; Lower education level was associated with lower risk of ASD, OR (95%CI) was 0.593 (0.359-0.978); People who are older, thinner, have a history of mental illness, and drink alcohol were at higher risk for PTSD, the values of OR (95%CI) were 20.144 (2.459-165.043), 10.287 (2.218-47.700), 91.104 (8.592-965.980) and 2.866 (1.144-7.180), respectively. Conclusion: Gender, age, education level, passive smoking, alcohol consumption, past history of mental illness and body mass index may be related to the potential risk of PTSD in rescue workers,passive smoking, alcohol consumption, and weight controlling should be focused on to reduce potential risks of PTSD.


Subject(s)
Male , Humans , Female , Young Adult , Adult , Stress Disorders, Post-Traumatic/prevention & control , Tobacco Smoke Pollution , Risk Assessment , Military Personnel , Alcohol Drinking
14.
J Microbiol Methods ; 200: 106547, 2022 09.
Article in English | MEDLINE | ID: mdl-35926680

ABSTRACT

BACKGROUND: The aim of the study was to evaluate a loop-mediated isothermal amplification (LAMP) assay for the ability to diagnose tuberculosis directly from clinical samples rapidly. METHODS: LAMP assays were performed using previously reported primer sets to amplify three specific Mycobacterium tuberculosis (MTB) gene targets, hspX, gyrB, and IS6110. Quantitated DNA from strain H37Rv were detected for assessment of analytical sensitivity; specificity was evaluated by testing eight species of non-tuberculosis Mycobacterium (NTM) and four unrelated bacterial species. Sputum samples from 68 pulmonary tuberculosis patients and a control group consisting of 45 lung cancer patients and 20 healthy controls were analyzed using LAMP assays, and then compared with smear, culture and quantitative real-time PCR (qRT-PCR) methods. RESULTS: All three LAMP assays showed 100% specificity for MTB when tested against NTM and other bacterial species. The gyrB-LAMP assay was able to detect 60 cfu/ml of H37Rv suspension within 1 h, similar to qRT-PCR, but 10 times more sensitive than the hspX-LAMP and IS6110-LAMP assays. In clinical samples, when qRT-PCR was used as the reference method, the sensitivity of the three LAMP assays targeting hspX, gyrB, and IS6110 genes was 94.6, 98.2 and 92.9%, respectively. CONCLUSIONS: LAMP is more sensitive than smear microscopy and close to qRT-PCR in sensitivity for the detection of MTB. LAMP has comparable specificity to qRT-PCR but was more rapid and convenient.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Lymph Node , Humans , Molecular Diagnostic Techniques , Mycobacterium tuberculosis/genetics , Nontuberculous Mycobacteria/genetics , Nucleic Acid Amplification Techniques/methods , Sensitivity and Specificity , Sputum/microbiology
15.
Biomed Res Int ; 2022: 6871269, 2022.
Article in English | MEDLINE | ID: mdl-35915804

ABSTRACT

Macrophages play an essential role in the pathogenesis of most inflammatory diseases. Recent studies have shown that mechanical load can influence macrophage function, leading to excessive and uncontrolled inflammation and even systemic damage, including cardiovascular disease and knee osteoarthritis. However, the molecular mechanism remains unclear. In this study, murine RAW264.7 cells were treated with mechanical stretch (MS) using the Flexcell-5000T Tension System. The expression of inflammatory factors and cytokine release were measured by RT-qPCR, ELISA, and Western blotting. The protein expression of NF-κB p65, Iκb-α, p-Iκb-α, RhoA, ROCK1, and ROCK2 was also detected by Western blotting. Then, Flow cytometry was used to detect the proportion of macrophage subsets. Meanwhile, Y-27632 dihydrochloride, a ROCK inhibitor, was added to knockdown ROCK signal transduction in cells. Our results demonstrated that MS upregulated mRNA expression and increased the secretion levels of proinflammatory factors iNOS, IL-1ß, TNF-α, and IL-6. Additionally, MS significantly increased the proportion of CD11b+CD86+ and CD11b+CD206+ subsets in RAW264.7 macrophages. Furthermore, the protein expression of RhoA, ROCK1, ROCK2, NF-κB p65, and IκB-α increased in MS-treated RAW264.7 cells, as well as the IL-6 and iNOS. In contrast, ROCK inhibitor significantly blocked the activation of RhoA-ROCK and NF-κB pathway, decreased the protein expression of IL-6 and iNOS, reduced the proportion of CD11b+CD86+ cells subpopulation, and increased the proportion of CD11b+CD206+ cell subpopulation after MS. These data indicate that mechanical stretch can regulate the RAW264.7 macrophage polarization and enhance inflammatory responses in vitro, which may contribute to activation the RhoA-ROCK/NF-κB pathway.


Subject(s)
NF-kappa B , rho-Associated Kinases , Animals , Inflammation/metabolism , Interleukin-6/metabolism , Lipopolysaccharides/metabolism , Macrophages/metabolism , Mice , NF-KappaB Inhibitor alpha/metabolism , NF-kappa B/metabolism , rho-Associated Kinases/genetics , rho-Associated Kinases/metabolism , rhoA GTP-Binding Protein/metabolism
16.
Cell Prolif ; 55(5): e13214, 2022 May.
Article in English | MEDLINE | ID: mdl-35411556

ABSTRACT

OBJECTIVES: To restore tissue growth without increasing the risk for cancer during aging, there is a need to identify small molecule drugs that can increase cell growth without increasing cell proliferation. While there have been numerous high-throughput drug screens for cell proliferation, there have been few screens for post-mitotic anabolic growth. MATERIALS AND METHODS: A machine learning (ML)-based phenotypic screening strategy was used to discover metabolites that boost muscle growth. Western blot, qRT-PCR and immunofluorescence staining were used to evaluate myotube hypertrophy/maturation or protein synthesis. Mass spectrometry (MS)-based thermal proteome profiling-temperature range (TPP-TR) technology was used to identify the protein targets that bind the metabolites. Ribo-MEGA size exclusion chromatography (SEC) analysis was used to verify whether the ribosome proteins bound to calcitriol. RESULTS: We discovered both the inactive cholecalciferol and the bioactive calcitriol are amongst the top hits that boost post-mitotic growth. A large number of ribosomal proteins' melting curves were affected by calcitriol treatment, suggesting that calcitriol binds to the ribosome complex directly. Purified ribosomes directly bound to pure calcitriol. Moreover, we found that calcitriol could increase myosin heavy chain (MHC) protein translation and overall nascent protein synthesis in a cycloheximide-sensitive manner, indicating that calcitriol can directly bind and enhance ribosomal activity to boost muscle growth. CONCLUSION: Through the combined strategy of ML-based phenotypic screening and MS-based omics, we have fortuitously discovered a new class of metabolite small molecules that can directly activate ribosomes to promote post-mitotic growth.


Subject(s)
Calcitriol , Cholecalciferol , Calcitriol/pharmacology , Cell Proliferation , Cholecalciferol/metabolism , Cholecalciferol/therapeutic use , Machine Learning , Ribosomes/metabolism
17.
Org Lett ; 24(11): 2087-2092, 2022 Mar 25.
Article in English | MEDLINE | ID: mdl-35285642

ABSTRACT

The Pd(II)-catalyzed C-H bond activation/C-N bond cleavage annulation reaction of N-alkyoxyamide aryne is developed to synthesize 9,10-dihydrophenanthrenone derivatives. This reaction exhibited good functional group compatibility with yields up to 92%. Detailed mechanistic studies showed that the key to C-N bond cleavage is the formed eight-membered palladacycle intermediate undergoing nucleophilic addition to the carbonyl group, which provides a new and practical way for N-alkoxyamide directed C-H bond activation.

18.
J Cachexia Sarcopenia Muscle ; 13(2): 781-794, 2022 04.
Article in English | MEDLINE | ID: mdl-35106971

ABSTRACT

Age-associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation leads to the redistribution of fat to the intra-abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing ß-oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro-inflammatory cytokines. In turn, these muscle-secreted cytokines may exacerbate adipose tissue atrophy, support chronic low-grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full-blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the 'obesity paradox', could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full-blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.


Subject(s)
Sarcopenia , Adipose Tissue/pathology , Aged , Aged, 80 and over , Aging/physiology , Humans , Muscle, Skeletal/pathology , Obesity/pathology , Sarcopenia/etiology , Sarcopenia/pathology
19.
Lab Med ; 53(5): e123-e125, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35075476

ABSTRACT

Microbial cultivation is the current gold standard for the clinical diagnosis of bacterial infections. However, this method sometimes produces false negative results. We present a case study of multisite Pseudomonas aeruginosa infections detected by metagenomic next-generation sequencing in a child with aplastic anemia, highlighting the rapid and accurate advantages of this technique.


Subject(s)
Anemia, Aplastic , Pseudomonas Infections , Anemia, Aplastic/diagnosis , Child , High-Throughput Nucleotide Sequencing/methods , Humans , Metagenomics/methods , Pseudomonas Infections/diagnosis , Pseudomonas Infections/microbiology
20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-958677

ABSTRACT

Objective:To solve the dilemma between the traditional ethics review management model and the fast development of biomedical research involving human subject, and to effectively summarize the practical experience to improve the efficiency of ethics review.Methods:A series of measures, such as reorganizing the ethics committee, adjusting the operating procedures of the office and optimizing the process of joint review were reviewed and summarized. The successful experience of relevant measures is systematically shared in practice.Results:The practice proved that these measures effectively guaranteed the fast development of clinical trials and research in our hospital during the past two years.Conclusions:The author hopes to strengthen the discussion and exchange with professionals in the industry through the successful practical experience of our hospital, and contribute to the improvement of the level of ethical management in China.

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