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1.
Front Vet Sci ; 11: 1446743, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39323871

RESUMEN

A new species of nematode, Molinostrongylus longmenensis n.sp., parasite of the genus Molinostrongylus, is described based on specimens recovered from the small intestine of Scotophilus kuhlii Leach, 1822 (Chiroptera: Vespertilionidae) in Longmen County, Guangdong Province, China. To date, 135 species of bat-parasitic nematodes have been reported worldwide. Overall, 13 species belonging to seven genera in three families have been described in China. The new species is characterized by the presence of three ventral and three dorsal longitudinal cuticular ridges perpendicular to the body surface, which appear posterior to the cephalic vesicle and extend to the caudal bursa in males and the posterior end in females. The female tail has two medium-sized subventral conical processes of equal length, as well as one large dorsal conical process, and one thin spine, lateral alae that extend to the position of the vulva, with a fin-like ending. In addition, the new species was also characterized using molecular approaches, such as sequencing and analyzing the internal transcribed spacer 1 (ITS-1) of the ribosomal DNA.

2.
Sci Total Environ ; 954: 176416, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39306121

RESUMEN

Developing rapid and sensitive methods for monitoring inorganic mercury (Hg2+) and methylmercury (CH3Hg+) in crayfish is crucial for understanding the environmental impact of these contaminants. In this work, a novel tri-mode strategy was developed for highly sensitive monitoring of Hg2+ and CH3Hg+ bioaccumulation in crayfish by inductively coupled plasma mass spectrometry (ICP-MS)/ fluorescence /smartphone colorimetric (RGB) analysis without chromatographic separation. Cation exchange reaction (CER) was performed between Hg2+ and luminescent CdTe quantum dots (QDs), while CH3Hg+ unrealizable CER. The CH3Hg+ can be transformed to Hg2+ by simple UV irradiation, speciation analysis can be realized by detecting the fluorescence of CdTe QDs after incubation by Hg2+ and total Hg2+. In addition, the filtration of reacted CdTe QDs was carried out, ICP-MS was performed to detect exchanged Cd2+ by Hg2+ and total Hg2+, as well the smartphone RGB analysis was performed for membrane colorimetry. The limits of detection (LODs) of Hg2+ and CH3Hg+ for ICP-MS, fluorescence, and colorimetric (RGB) modes were 0.03 ng mL-1, 18 ng mL-1, and 0.9 µg mL-1 respectively. Density Functional Theory (DFT) was employed to validate the mechanism of the CER reaction. CdTe QDs array analysis with five different ligands was performed to eliminate potential ion interferences of Ag+ and Cu2+ that could occur during the CER reaction. The well-designed system was successfully utilized for monitoring trace Hg2+ and CH3Hg+ in crayfish fed Hg2+ and CH3Hg+ contaminative food over a two-week "uptake" period and a three-week "depuration" period. The results indicated that the Hg2+ uptake in different tissues was significantly different from that of CH3Hg+ in all tissues. There was evidence of Hg uptake from water via leaching from food, although the principal source of uptake was from food.

3.
ChemSusChem ; : e202401091, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39115021

RESUMEN

Developing energy- and time-efficient strategies to derive high-performance non-precious electrocatalysts for anodic oxygen evolution reaction (OER), especially stably working at industrial-demanding current density, is still a big challenge. In this work, a concise molten salt erosion scenario was devised to rapidly modulate the smooth surface of the commercial NiMo foam substrate into the rough, electronically coupled, and hierarchically porous Ni/Fe/Mo(oxy)hydroxide catalyst layer assembled by the nanosphere array. This self-supported catalyst is super-hydrophilic for the alkaline electrolyte and distinguished by a balanced Mo leaching/surface-readsorption process to tune the metal d band center and electronic perturbation. The altered electronic environment with the favored OER intermediate adsorption behavior attains the outstanding OER activity in terms of a very small overpotential of 230.21 mV at 10 mA cm-2 and an ultra-long stability for 1179.45 h to sustain the initial commercial-level current density of ca. 1000 mA cm-2. This superb performance transcends most of the edge-cutting transition metal peers reported recently and can satisfy the standards of industrial applications. This industrial-compatible synthesis technology holds profound implications for hydrogen production via water splitting and other electrochemical applications.

4.
Nat Commun ; 15(1): 7191, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39168995

RESUMEN

Quantum spin liquids (QSLs) have become a key area of research in magnetism due to their remarkable properties, such as long-range entanglement, fractional excitations, and topologically protected phenomena. Recently, the search for QSLs has expanded into the three-dimensional world, despite the suppression of quantum fluctuations due to high dimensionality. A new candidate material, K2Ni2(SO4)3, belongs to the langbeinite family and consists of two interconnected trillium lattices. Although magnetically ordered, it exhibits a highly dynamical and correlated state. In this work, we combine inelastic neutron scattering measurements with density functional theory (DFT), pseudo-fermion functional renormalization group (PFFRG), and classical Monte Carlo (cMC) calculations to study the magnetic properties of K2Ni2(SO4)3, revealing a high level of agreement between experiment and theory. We further reveal the origin of the dynamical state in K2Ni2(SO4)3 to be centred around a magnetic network composed of tetrahedra on a trillium lattice.

5.
Chem Sci ; 15(29): 11311-11320, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39055035

RESUMEN

Homogeneous gold catalysis has attracted much recent attention due to diverse activation modes of gold(i) towards unsaturated organic groups. Because of attractive aurophilic interaction, structural transformations of metalated species into high nuclear clusters are often proposed in gold catalysis, while to date little is known about their assembly behaviors and catalytic activity. In this work, based on stoichiometric Au(i)-mediated enyne cyclization reactions, we achieve a discrete vicinal dicarbanion-centered Au4 intermediate and three assembled Au11, Au28, and Au14 clusters held together by several aryl dicarbanions. Spectral monitoring, kinetic and theoretical investigations confirm that these discrete and assembled intermediates display four different pathways upon catalyzing the cyclization reaction of the same 1,5-enyne substrate. The discrete Au4 cluster undergoes a full protodeauration process to generate active [Au(PPh3)]+ species for catalytic use. In contrast, the net-like Au11 cluster experiences a substrate-induced dissociation to generate a semi-stable Au10 unit and an active [alkyne-Au(PPh3)]+ fragment for further transformation. The dumbbell-like Au28 cluster is prone to cleavage of the central Au-Au linkage and each Au14 moiety exposes a coordination unsaturated site to activate a substrate molecule. However, the synthetic closed-Au14 cluster with full ligand protection is no longer catalytically active.

6.
Lab Invest ; 104(8): 102090, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38830579

RESUMEN

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.


Asunto(s)
Antineoplásicos , Resistencia a Antineoplásicos , Inmunoterapia , Oxaliplatino , Neoplasias Gástricas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Inmunoterapia/métodos , Oxaliplatino/uso terapéutico , Oxaliplatino/farmacología , Pronóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/terapia
7.
Autophagy ; 20(10): 2238-2254, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38842055

RESUMEN

ATG10S is a newly discovered subtype of the autophagy protein ATG10. It promotes complete macroautophagy/autophagy, degrades multiple viral proteins, and increases the expression of type III interferons. Here, we aimed to investigate the mechanism of ATG10S cooperation with IFNL1 to degrade viral proteins from different viruses. Using western blot, immunoprecipitation (IP), tandem sensor RFP-GFP-LC3B and in situ proximity ligation assays, we showed that exogenous recombinant ATG10S protein (rHsATG10S) could enter into cells through clathrin, and ATG10S combined with ATG7 with IFNL1 assistance to facilitate ATG12-ATG5 conjugation, thereby contributing to the autophagosome formation in multiple cell lines containing different virions or viral proteins. The results of DNA IP and luciferase assays also showed that ATG10S was able to directly bind to a core motif (CAAGGG) within a binding site of transcription factor ZNF460 on the IFNL1 promoter, by which IFNL1 transcription was activated. These results clarified that ATG10S promoted autophagosome formation with the assistance of IFNL1 to ensure autophagy flux and autophagic degradation of multiple viral proteins and that ATG10S could also act as a novel transcription factor to promote IFNL1 gene expression. Importantly, this study further explored the antiviral mechanism of ATG10S interaction with type III interferon and provided a theoretical basis for the development of ATG10S into a new broad-spectrum antiviral protein drug.Abbreviation: ATG: autophagy related; ATG10S: the shorter isoform of autophagy-related 10; CC50: half cytotoxicity concentration; CCV: clathrin-coated transport vesicle; CLTC: clathrin heavy chain; CM: core motif; co-IP: co-immunoprecipitation; CPZ: chlorpromazine; ER: endoplasmic reticulum; HCV: hepatitis C virus; HBV: hepatitis B virus; HsCoV-OC43: Human coronavirus OC43; IFN: interferon; PLA: proximity ligation assay; rHsATG10S: recombinant human ATG10S protein; RLU: relative light unit; SQSTM1: sequestosome 1; ZNF: zinc finger protein.


Asunto(s)
Proteínas Relacionadas con la Autofagia , Autofagia , Proteínas Virales , Humanos , Autofagia/fisiología , Proteínas Relacionadas con la Autofagia/metabolismo , Proteínas Virales/metabolismo , Interferones/metabolismo , Interferón lambda , Células HEK293 , Regiones Promotoras Genéticas/genética , Autofagosomas/metabolismo , Interleucinas/metabolismo , Proteína 5 Relacionada con la Autofagia/metabolismo , Proteína 5 Relacionada con la Autofagia/genética , Proteína 7 Relacionada con la Autofagia/metabolismo , Proteína 7 Relacionada con la Autofagia/genética , Unión Proteica , Proteínas de Transporte Vesicular
8.
PLoS Negl Trop Dis ; 18(5): e0012159, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38739673

RESUMEN

BACKGROUND: Rodents are recognized as the hosts of many vector-borne bacteria and protozoan parasites and play an important role in their transmission and maintenance. Intensive studies have focused on their infections in vectors, especially in ticks, however, vector-borne bacterial and protozoan infections in rodents are poorly understood although human cases presenting with fever may due to their infection have been found. METHODS: From May to October 2019, 192 wild rodents were trapped in wild environment of Guangxi Province, and the spleen samples were collected to reveal the presence of vector-borne bacterial and protozoan infections in them. The microorganisms in rodents were identified by detecting their DNA using (semi-)nested PCR. All the PCR products of the expected size were subjected to sequencing, and then analyzed by BLASTn. Furthermore, all the recovered sequences were subjected to nucleotide identity and phylogenetic analyses. RESULTS: As a result, 192 rodents representing seven species were captured, and Bandicota indica were the dominant species, followed by Rattus andamanensis. Based on the (semi-)nested PCR, our results suggested that Anaplasma bovis, Anaplasma capra, Anaplasma ovis, Anaplasma phagocytophilum, "Candidatus Neoehrlichia mikurensis", "Candidatus E. hainanensis", "Candidatus E. zunyiensis", three uncultured Ehrlichia spp., Bartonella coopersplainsensis, Bartonella tribocorum, Bartonella rattimassiliensis, Bartonella silvatica, two uncultured Bartonella spp., Babesia microti and diverse Hepatozoon were identified in six rodent species. More importantly, six species (including two Anaplasma, two Bartonella, "Ca. N. mikurensis" and Bab. microti) are zoonotic pathogens except Anaplasma bovis and Anaplasma ovis with zoonotic potential. Furthermore, dual infection was observed between different microorganisms, and the most common type of co-infection is between "Ca. N. mikurensis" and other microorganisms. Additionally, potential novel Bartonella species and Hepatozoon species demonstrated the presence of more diverse rodent-associated Bartonella and Hepatozoon. CONCLUSIONS: The results in this work indicated great genetic diversity of vector-borne infections in wild rodents, and highlighted the potential risk of human pathogens transmitted from rodents to humans through vectors.


Asunto(s)
Variación Genética , Roedores , Animales , China/epidemiología , Roedores/microbiología , Roedores/parasitología , Filogenia , Animales Salvajes/parasitología , Animales Salvajes/microbiología , Anaplasma/genética , Anaplasma/aislamiento & purificación , Anaplasma/clasificación , Enfermedades Transmitidas por Vectores/transmisión , Enfermedades Transmitidas por Vectores/microbiología , Enfermedades Transmitidas por Vectores/parasitología , Enfermedades Transmitidas por Vectores/epidemiología , Bartonella/genética , Bartonella/aislamiento & purificación , Bartonella/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/clasificación , Ratas
9.
Int J Mol Sci ; 25(10)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38791126

RESUMEN

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common metabolic disease of the liver, characterized by hepatic steatosis in more than 5% of hepatocytes. However, despite the recent approval of the first drug, resmetirom, for the management of metabolic dysfunction-associated steatohepatitis, decades of target exploration and hundreds of clinical trials have failed, highlighting the urgent need to find new druggable targets for the discovery of innovative drug candidates against MASLD. Here, we found that glutathione S-transferase alpha 1 (GSTA1) expression was negatively associated with lipid droplet accumulation in vitro and in vivo. Overexpression of GSTA1 significantly attenuated oleic acid-induced steatosis in hepatocytes or high-fat diet-induced steatosis in the mouse liver. The hepatoprotective and anti-inflammatory drug bicyclol also attenuated steatosis by upregulating GSTA1 expression. A detailed mechanism showed that GSTA1 directly interacts with fatty acid binding protein 1 (FABP1) and facilitates the degradation of FABP1, thereby inhibiting intracellular triglyceride synthesis by impeding the uptake and transportation of free fatty acids. Conclusion: GSTA1 may be a good target for the discovery of innovative drug candidates as GSTA1 stabilizers or enhancers against MASLD.


Asunto(s)
Proteínas de Unión a Ácidos Grasos , Hígado Graso , Glutatión Transferasa , Regulación hacia Arriba , Glutatión Transferasa/metabolismo , Glutatión Transferasa/genética , Animales , Humanos , Ratones , Proteínas de Unión a Ácidos Grasos/metabolismo , Proteínas de Unión a Ácidos Grasos/genética , Hígado Graso/metabolismo , Hígado Graso/tratamiento farmacológico , Regulación hacia Arriba/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hígado/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Masculino , Ratones Endogámicos C57BL , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Ácido Oléico/metabolismo , Células Hep G2 , Triglicéridos/metabolismo , Isoenzimas
10.
World J Pediatr ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713366

RESUMEN

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

11.
Eur J Med Res ; 29(1): 180, 2024 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-38494472

RESUMEN

BACKGROUND: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. METHODS: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. RESULTS: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). CONCLUSIONS: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients.


Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Pronóstico , Biomarcadores , Inmunoterapia , Microambiente Tumoral/genética , Complejo IV de Transporte de Electrones
12.
Mol Cancer Ther ; 23(7): 939-948, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38490257

RESUMEN

Carcinoembryonic antigen-related cell adhesion molecules (CEACAM), such as carcinoembryonic antigen (CEA) and the oncofetal glycoprotein family, are tumor markers. The CEACAMs consist of 12 different human CEACAMs and 5 different murine CEACAMs. The CEACAM family of proteins participates in multiple biological processes that include the immune response, angiogenesis, and cancer. CEACAMs play a significant role in cancer initiation and development. Increasing evidence suggests that family members may be new cancer biomarkers and targets in that CEACEAMs tend to be aberrantly expressed and therefore may have potential diagnostic and therapeutic importance. This review systematically summarizes the biogenesis, biological properties, and functions of CEACAMs, with a focus on their relationship with cancer and potential clinical application. As our knowledge of the relationships among CEACAMs and cancer increases, and as our understanding of the involved molecular mechanisms improves, new therapeutic strategies will evolve for cancer prevention and treatment of patients with cancer.


Asunto(s)
Antígeno Carcinoembrionario , Moléculas de Adhesión Celular , Neoplasias , Humanos , Neoplasias/metabolismo , Antígeno Carcinoembrionario/metabolismo , Moléculas de Adhesión Celular/metabolismo , Animales , Biomarcadores de Tumor/metabolismo
13.
Front Vet Sci ; 11: 1373178, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38550787

RESUMEN

Background: Dogs and cats are the hosts of many vector-borne human pathogens that can be transmitted to humans. Given their direct and intimate contact with humans, companion dogs and cats are considered direct sentinels of vector-borne human pathogens. However, limited information is currently available regarding canine and feline zoonotic pathogens in China. This study detected canine and feline vector-borne human pathogens to better understand the potential risk to humans. Methods: Blood samples were collected from 275 domestic companion animals (117 dogs and 158 cats) living in Tianjin city, China, and the presence of DNA from Anaplasma, Babesia, Bartonella, and Rickettsia was detected by semi-nested polymerase chain reaction (PCR). The PCR products of the expected size were sequenced, and these newly generated sequences were subjected to BLASTN, nucleotide identity, and phylogenetic analyses. Results: A total of 24 blood samples tested positive for vector-borne pathogens in companion dogs and cats in Tianjin city, China, with a relatively low positive rate of 8.7%. Specifically, seven human pathogens, including Rickettsia raoultii, Candidatus Rickettsia jingxinensis, Rickettsia sibirica, Rickettsia felis, Babesia venatorum, Bartonella tribocorum, and Bartonella Henselae, were identified. In addition, Anaplasma ovis with zoonotic potential and Candidatus A. cinensis were detected. Conclusion: Our results indicate substantial genetic diversity in the vector-borne human pathogens circulating in companion dogs and cats. Interventions based on "One Health" should be taken to reduce the potential risks of contracting infection from companion dogs and cats in Tianjin, China.

14.
Gut Microbes ; 16(1): 2304159, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38277137

RESUMEN

Gut microbiota plays an essential role in the progression of nonalcoholic fatty liver disease (NAFLD), making the gut-liver axis a potential therapeutic strategy. Bacteroides genus, the enriched gut symbionts, has shown promise in treating fatty liver. However, further investigation is needed to identify specific beneficial Bacteroides strains for metabolic disorders in NAFLD and elucidate their underlying mechanisms. In this study, we observed a positive correlation between the abundance of Bacteroides thetaiotaomicron (B. theta) and the alleviation of metabolic syndrome in the early and end stages of NAFLD. Administration of B. theta to HFD-fed mice for 12 weeks reduced body weight and fat accumulation, decreased hyperlipidemia and insulin resistance, and prevented hepatic steatohepatitis and liver injury. Notably, B. theta did not affect these indicators in low-fat diet (LFD)-fed mice and exhibited good safety. Mechanistically, B. theta regulated gut microbial composition, characterized by a decreased Firmicutes/Bacteroidetes ratio in HFD-Fed mice. It also increased gut-liver folate levels and hepatic metabolites, alleviating metabolic dysfunction. Additionally, treatment with B. theta increased the proportion of polyunsaturated fatty acid in the mouse liver, offering a widely reported benefit for NAFLD improvement. In conclusion, this study provides evidence that B. theta ameliorates NAFLD by regulating gut microbial composition, enhancing gut-liver folate and unsaturated fatty acid metabolism, highlighting the therapeutic role of B. theta as a potential probiotic for NAFLD.


Asunto(s)
Bacteroides thetaiotaomicron , Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , Ratones Endogámicos C57BL
16.
Nat Med ; 30(2): 552-559, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38167937

RESUMEN

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .


Asunto(s)
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Adenocarcinoma/patología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Anticuerpos Monoclonales Humanizados/efectos adversos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
17.
J Phys Condens Matter ; 36(15)2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38171024

RESUMEN

We establish the sign of the linear magnetoelectric (ME) coefficient,α, in chromia, Cr2O3. Cr2O3is the prototypical linear ME material, in which an electric (magnetic) field induces a linearly proportional magnetization (polarization), and a single magnetic domain can be selected by annealing in combined magnetic (H) and electric (E) fields. Opposite antiferromagnetic (AFM) domains have opposite ME responses, and which AFM domain corresponds to which sign of response has previously been unclear. We use density functional theory (DFT) to calculate the magnetic response of a single AFM domain of Cr2O3to an applied in-plane electric field at zero kelvin. We find that the domain with nearest neighbor magnetic moments oriented away from (towards) each other has a negative (positive) in-plane ME coefficient,α⊥, at zero kelvin. We show that this sign is consistent with all other DFT calculations in the literature that specified the domain orientation, independent of the choice of DFT code or functional, the method used to apply the field, and whether the direct (magnetic field) or inverse (electric field) ME response was calculated. Next, we reanalyze our previously published spherical neutron polarimetry data to determine the AFM domain produced by annealing in combinedEandHfields oriented along the crystallographic symmetry axis at room temperature. We find that the AFM domain with nearest-neighbor magnetic moments oriented away from (towards) each other is produced by annealing in (anti-)parallelEandHfields, corresponding to a positive (negative) axial ME coefficient,α∥, at room temperature. Sinceα⊥at zero kelvin andα∥at room temperature are known to be of opposite sign, our computational and experimental results are consistent.

18.
Nat Commun ; 15(1): 442, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38200029

RESUMEN

In quantum magnetic materials, ordered phases induced by an applied magnetic field can be described as the Bose-Einstein condensation (BEC) of magnon excitations. In the strongly frustrated system SrCu2(BO3)2, no clear magnon BEC could be observed, pointing to an alternative mechanism, but the high fields required to probe this physics have remained a barrier to detailed investigation. Here we exploit the first purpose-built high-field neutron scattering facility to measure the spin excitations of SrCu2(BO3)2 up to 25.9 T and use cylinder matrix-product-states (MPS) calculations to reproduce the experimental spectra with high accuracy. Multiple unconventional features point to a condensation of S = 2 bound states into a spin-nematic phase, including the gradients of the one-magnon branches and the persistence of a one-magnon spin gap. This gap reflects a direct analogy with superconductivity, suggesting that the spin-nematic phase in SrCu2(BO3)2 is best understood as a condensate of bosonic Cooper pairs.

19.
Infect Genet Evol ; 115: 105506, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37742909

RESUMEN

China was affected severely by tick-borne rickettsiosis, and more than 10 Rickettsia species pathogenic to humans have been identified. In recent years, several Rickettsia members, with unknown pathogenicity, firstly identified abroad have been found in China. In this study, parasitic and questing ticks were recovered from two sampling sites in Hebei, China. Specific primers targeting outer membrane protein B (ompB) gene were designed to test the presence of Rickettsia canadensis by nested Polymerase Chain Reaction (PCR). As a result, a total of 428 ticks, including 232 ticks (including 230 Haemaphysalis longicornis and two H. japonica) from Laiyuan County and 196 (H. longicornis) from Luanping County, were collected. Sequencing of PCR products with the expected size and subsequently BLAST showed that 38H. longicornis ticks tested positive for R. canadensis, with an overall positive rate of 8.8%. In addition, 800-bp ompB gene and nearly complete citrate synthase (gltA) gene were recovered from six randomly selected positive samples to better understand their genetic characteristics. Nucleotide identity and phylogenetic analyses showed that R. canadensis presented geographical clustering with evidence that variants identified in the current study presented closer genetic relationship with others identified in Asian than those found in North America. In addition, epidemiological data suggested that H. longicornis may be the competent vector, and more attention should be paid to R. canadensis due to its zoonotic potential. In sum, R. canadensis was confirmed to be present in Hebei Province, China, and its surveillance in ticks should be strengthened due to potential pathogenicity, higher positive rate in ticks and wide distribution of possible vector tick species.


Asunto(s)
Ixodidae , Rickettsia , Garrapatas , Humanos , Animales , Garrapatas/microbiología , Filogenia , Rickettsia/genética , China/epidemiología
20.
Front Physiol ; 14: 1182719, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37469560

RESUMEN

Background: Ventricular septal defect is a common congenital heart disease. As the disease progresses, the likelihood of lung infection and heart failure increases, leading to prolonged hospital stays and an increased likelihood of complications such as nosocomial infections. We aimed to develop a nomogram for predicting hospital stays over 14 days in pediatric patients with ventricular septal defect and to evaluate the predictive power of the nomogram. We hope that nomogram can provide clinicians with more information to identify high-risk groups as soon as possible and give early treatment to reduce hospital stay and complications. Methods: The population of this study was pediatric patients with ventricular septal defect, and data were obtained from the Pediatric Intensive Care Database. The resulting event was a hospital stay longer than 14 days. Variables with a variance inflation factor (VIF) greater than 5 were excluded. Variables were selected using the least absolute shrinkage and selection operator (Lasso), and the selected variables were incorporated into logistic regression to construct a nomogram. The performance of the nomogram was assessed by using the area under the receiver operating characteristic curve (AUC), Decision Curve Analysis (DCA) and calibration curve. Finally, the importance of variables in the model is calculated based on the XGboost method. Results: A total of 705 patients with ventricular septal defect were included in the study. After screening with VIF and Lasso, the variables finally included in the statistical analysis include: Brain Natriuretic Peptide, bicarbonate, fibrinogen, urea, alanine aminotransferase, blood oxygen saturation, systolic blood pressure, respiratory rate, heart rate. The AUC values of nomogram in the training cohort and validation cohort were 0.812 and 0.736, respectively. The results of the calibration curve and DCA also indicated that the nomogram had good performance and good clinical application value. Conclusion: The nomogram established by BNP, bicarbonate, fibrinogen, urea, alanine aminotransferase, blood oxygen saturation, systolic blood pressure, respiratory rate, heart rate has good predictive performance and clinical applicability. The nomogram can effectively identify specific populations at risk for adverse outcomes.

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