Phospholipase D regulates ferroptosis signal transduction in mouse spleen hypoxia response

High-altitude hypoxia exposure can lead to phospholipase D-mediated lipid metabolism disorder in spleen tissues and induce ferroptosis. Nonetheless, the key genes underlying hypoxia-induced splenic phospholipase D and the ferroptosis pathway remain unclear. This study aimed to establish a hypoxia animal model. Combined transcriptomic and proteomic analyses showed that 95 predicted target genes (proteins) were significantly differentially expressed under hypoxic conditions. Key genes in phospholipase D and ferroptosis pathways under hypoxic exposure were identified by combining Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis techniques. Gene set enrichment analysis (GSEA) showed that the differential gene sets of the phospholipase D and ferroptosis signaling pathways were upregulated in the high-altitude hypoxia group. The genes in the phospholipase D signalling pathway were verified, and the expression levels of KIT and DGKG were upregulated in spleen tissues under hypoxic exposure. Subsequently, the mRNA and protein expression levels of genes from the exogenous pathway such as TFRC, SLC40A1, SLC7A11, TRP53, and FTH1 and those from the endogenous pathway such as GPX4, HMOX1, and ALOX15 differentials in the ferroptosis signalling pathway were verified, and the results indicated significant differential expression. In summary, exposure to high-altitude hypoxia mediated phospholipid metabolism disturbance through the phospholipase D signalling pathway and further induced ferroptosis, leading to splenic injury.

Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway

Abstract The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.

Physical Fitness Parameters of Elite Chinese Wheelchair Curlers / Parámetros de Aptitud Física de Curlers en Silla de Ruedas Chinos de Élite

SUMMARY: Few international studies have analyzed the characteristics of elite wheelchair curlers competing on the international stage. This study aims to investigate the physical fitness parameters of elite Chinese wheelchair curlers and explore the corresponding training enlightenment. Sixteen wheelchair curlers from the Chinese national team, including six male and two female Winter Paralympic gold medalists, were selected as research participants. The following parameters were measured: age, training age, height, weight, body fat percentage, grip strength, absolute bench press strength, and 5-km wheelchair push-timing test. Compared with ordinary curlers of the Chinese wheelchair curling team, elite curlers were older in age and training age; male curlers were shorter, whereas female curlers were taller. However, their weight and body fat percentage were lower, and their grip strength, absolute strength in the bench press, and 5-k wheelchair push-timing test were better. From an athlete development and physical training perspective, wheelchair curlers should increase training years in order to accumulate competition experience. Additionally, these athletes should manage their body weight and fat percentage, and improve their upper limb strength and aerobic capacity.

Pocos estudios internacionales han analizado las características de los curlers en silla de ruedas de élite que compiten en el escenario internacional. Este estudio tiene como objetivo investigar los parámetros de aptitud física de los bigudíes chinos en silla de ruedas de élite y explorar la iluminación del entrenamiento correspondiente. Se seleccionaron como participantes de la investigación dieciséis curlers en silla de ruedas del equipo nacional chino, incluidos seis medallistas de oro masculinos y dos femeninos de los Juegos Paralímpicos de Invierno. Se midieron los siguientes parámetros: edad, edad de entrenamiento, altura, peso, porcentaje de grasa corporal, fuerza de agarre, fuerza absoluta en press de banca y prueba de sincronización de empuje en silla de ruedas de 5 km. En comparación con los curlers ordinarios del equipo chino de curling en silla de ruedas, los curlers de élite eran mayores en edad y tiempo de entrenamiento; Los curlers masculinos eran más bajos, mientras que las mujeres eran más altas. Sin embargo, su peso y porcentaje de grasa corporal fueron menores, y su fuerza de agarre, fuerza absoluta en press de banca y prueba de sincronización de empuje en silla de ruedas de 5-k fueron mejores. Desde la perspectiva del desarrollo del atleta y del entrenamiento físico, los curlers en silla de ruedas deberían aumentar los años de entrenamiento para acumular experiencia en competencia. Además, estos deportistas deben controlar su peso corporal y porcentaje de grasa, y mejorar la fuerza de sus miembros superiores y su capacidad aeróbica.

Overexpression SPRY2 Suppresses Esophageal Squamous Cell Carcinoma Progression Via Inactivation of ERK/AKT Signaling / La Sobreexpresión SPRY2 Suprime la Evolución del Carcinoma de Células Escamosas de Esófago Mediante la Inactivación de la Señalización ERK/AKT

SUMMARY: Esophageal cancer is one of the most aggressive gastrointestinal cancers. Invasion and metastasis are the main causes of poor prognosis of esophageal cancer. SPRY2 has been reported to exert promoting effects in human cancers, which controls signal pathways including PI3K/AKT and MAPKs. However, the expression of SPRY2 in esophageal squamous cell carcinoma (ESCC) and its underlying mechanism remain unclear. In the present study, we aimed to investigate the detailed role of SPRY2 in the regulation of cell proliferation, invasion and ERK/AKT signaling pathway in ESCC. It was identified that the expression level of SPRY2 in ESCC was remarkably decreased compared with normal tissues, and it was related to clinicopathologic features and prognosis ESCC patients. The upregulation of SPRY2 expression notably inhibited the proliferation, migration and invasion of Eca-109 cells. In addition, the activity of ERK /AKT signaling was also suppressed by the SPRY2 upregulation in Eca-109 cells. Our study suggests that overexpression of SPRY2 suppress cancer cell proliferation and invasion of by through suppression of the ERK/AKT signaling pathways in ESCC. Therefore, SPRY2 may be a promising prognostic marker and therapeutic target for ESCC.

El cáncer de esófago es uno de los cánceres gastrointestinales más agresivos. La invasión y la metástasis son las principales causas de mal pronóstico del cáncer de esófago. Se ha informado que SPRY2 ejerce efectos promotores en los cánceres humanos, que controla las vías de señales, incluidas PI3K/AKT y MAPK. Sin embargo, la expresión de SPRY2 en el carcinoma de células escamosas de esófago (ESCC) y su mecanismo subyacente aún no están claros. En el presente estudio, nuestro objetivo fue investigar el papel detallado de SPRY2 en la regulación de la proliferación celular, la invasión y la vía de señalización ERK/AKT en ESCC. Se identificó que el nivel de expresión de SPRY2 en ESCC estaba notablemente disminuido en comparación con los tejidos normales, y estaba relacionado con las características clínico-patológicas y el pronóstico de los pacientes con ESCC. La regulación positiva de la expresión de SPRY2 inhibió notablemente la proliferación, migración e invasión de células Eca-109. Además, la actividad de la señalización de ERK/AKT también fue suprimida por la regulación positiva de SPRY2 en las células Eca-109. Nuestro estudio sugiere que la sobreexpresión de SPRY2 suprime la proliferación y la invasión de células cancerosas mediante la supresión de las vías de señalización ERK/AKT en ESCC. Por lo tanto, SPRY2 puede ser un marcador de pronóstico prometedor y un objetivo terapéutico para la ESCC.

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

Serum autophagy-related gene 5 level in stroke patients: correlation with CD4+ T cells and cognition impairment during a 3-year follow-up

Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.

Silencing of matrix metalloprotease-12 delays the progression of castration-resistant prostate cancer by regulating autophagy and lipolysis

Abstract The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways.

Periodontitis and osteoporosis: a two-sample Mendelian randomization analysis

Abstract The incidences of periodontitis and osteoporosis are rising worldwide. Observational studies have shown that periodontitis is associated with increased risk of osteoporosis. We performed a Mendelian randomization (MR) study to genetically investigate the causality of periodontitis on osteoporosis. We explored the causal effect of periodontitis on osteoporosis by MR analysis. A total of 9 single nucleotide polymorphisms (SNP) were related to periodontitis. The primary approach in this MR analysis was the inverse variance-weighted (IVW) method. Simple median, weighted median, and penalized weighted median were used to analyze sensitivity. The fixed-effect IVW model and random-effect IVW model showed no significant causal effect of genetically predicted periodontitis on the risk of osteoporosis (OR=1.032; 95%CI: 0.923-1.153; P=0.574; OR=1.032; 95%CI: 0.920-1.158; P=0.588, respectively). Similar results were observed in simple mode (OR=1.031; 95%CI: 0.780-1.361, P=0.835), weighted mode (OR=1.120; 95%CI: 0.944-1.328, P=0.229), simple median (OR=1.003; 95%CI: 0.839-1.197, P=0.977), weighted median (OR=1.078; 95%CI: 0.921-1.262, P=0.346), penalized weight median (OR 1.078; 95%CI: 0.919-1.264, P=0.351), and MR-Egger method (OR=1.360; 95%CI: 0.998-1.853, P=0.092). There was no heterogeneity in the IVW and MR-Egger analyses (Q=7.454, P=0.489 and Q=3.901, P=0.791, respectively). MR-Egger regression revealed no evidence of a pleiotropic influence through genetic variants (intercept: -0.004; P=0.101). The leave-one-out sensitivity analysis indicated no driven influence of any individual SNP on the association between periodontitis and osteoporosis. The Mendelian randomization analysis did not show a significant detrimental effect of periodontitis on the risk of osteoporosis.

Acute sarcoidosis Löfgren Syndrome treated by Chinese medicinal formula based on Syndrome Differentiation: a case - based review / Tratamiento de síndrome de Löfgren de sarcoidosis con fórmula medicinal china basada en diferenciación de síndrome: una revisión basada en casos

Löfgren syndrome (LS) is a unique acute manifestation of sarcoidosis and characterized by erythema nodosum, bilateral hilar lymphadenectasis, and/or bilateral ankle arthritis or periarthritis. A 37 - year - old female patient with LS presented with fever accompanied by multiple joint swelling and pain, nodular skin erythema, and bilateral hilar lymphadenectasis. The patient had received treatment involving non - steroidal anti - inflammatory drugs and glucocorticoids in other hospitals, but the effects were poor, and the conditions reemerged. The LS duration has lasted for more than 3 months. Following traditional Chinese medicine (TCM) treatment, syndrome differentiation as well as giving patients oral Chinese medicine decoction, the symptoms of the patient were rapidly relieved within one week and did not recur during a six - month follow - up period. This case is the first clinical report of acute sarcoidosis LS treated using T CM and reflects the significant advantages of this form of therapy in emergency treatment

El síndrome de Löfgren (LS) es una manifest ación única y aguda de sarcoidosis, caracterizada por eritrema nodoso, linfadenectasis hilar bilateral, y/o a r tritis de tobillo bilateral o periartritis. Una paciente de 37 años de sexo femenino con LS se presentó con fiebre, acompañada de inflamación y do lor múltiple de articulaciones, eritrema nodular cutáneo, y linfadenectasis hilar bilateral. La paciente recibió un tratamiento que consistió en antiinflamatorios no esteroidales y glucocorticoides en otros hospitales, pero los efectos fueron leves y las c ondiciones reemergieron. El LS ha durado más de tres meses. Siguiendo el tratamiento de medicina tradicional china (MTC), la diferenciación de síndrome, así como darles a los pacientes una decocción de medicina china por vía oral, los síntomas de la pacien te rápidamente fueron aliviados en el curso de una semana y no recidivaron durante los seis meses de un seguimiento. El caso es el primer reporte clínico de tratamiento de sarcoidosis aguda asociada a LS usando TCM y refleja las significativas ventajas de esta forma de terapia en el tratamiento de emergencia.

Variations in soil physico-chemical properties, soil stocks, and soil stoichiometry under different soil layers, the major forest region Liupan Mountains of Northwest China / Variações nas propriedades físico-químicas do solo, estoques e estequiometria do solo sob diferentes camadas de solo, a principal região florestal das montanhas Liupan do noroeste da China

Liupan Mountains are an important region in China in the context of forest cover and vegetation due to huge afforestation and plantation practices, which brought changes in soil physio-chemical properties, soil stocks, and soil stoichiometries are rarely been understood. The study aims to explore the distribution of soil nutrients at 1-m soil depth in the plantation forest region. The soil samples at five depth increments (0-20, 20-40, 40-60, 60-80, and 80-100 cm) were collected and analyzed for different soil physio-chemical characteristics. The results showed a significant variation in soil bulk density (BD), soil porosity, pH, cation exchange capacity (CEC), and electric conductivity (EC) values. More soil BD (1.41 g cm-3) and pH (6.97) were noticed in the deep soil layer (80-100 cm), while the highest values of porosity (60.6%), EC (0.09 mS cm-1), and CEC (32.9 c mol kg-1) were reflected in the uppermost soil layer (0-20 cm). Similarly, the highest contents of soil organic carbon (SOC), total phosphorus (TP), available phosphorus (AP), total nitrogen (TN), and available potassium (AK) were calculated in the surface soil layer (0-20 cm). With increasing soil depth increment a decreasing trend in the SOC and other nutrient concentration were found, whereas the soil total potassium (TK) produced a negative correlation with soil layer depth. The entire results produced the distribution of SOCs and TNs (stocks) at various soil depths in forestland patterns were 0→20cm > 20→40cm > 40→60cm ≥ 60→80cm ≥ 80→100 cm. Furthermore, the stoichiometric ratios of C, N, and P, the C/P, and N/P ratios showed maximum values (66.49 and 5.46) in 0-20 cm and lowest values (23.78 and 1.91) in 80-100 cm soil layer depth. Though the C/N ratio was statistically similar across the whole soil profile (0-100 cm). These results highlighted that the soil depth increments might largely be attributed to fluctuations in soil physio-chemical properties, soil stocks, and soil stoichiometries. Further study is needed to draw more conclusions on nutrient dynamics, soil stocks, and soil stoichiometry in these forests.

As montanhas de Liupan são uma região importante na China no contexto de cobertura florestal e vegetação devido às enormes práticas de florestamento e plantação, que trouxeram mudanças nas propriedades físico-químicas do solo, e estoques e estequiometrias do solo raramente são compreendidos. O estudo visa explorar a distribuição de nutrientes do solo a 1 m de profundidade do solo na região da floresta plantada. As amostras de solo em cinco incrementos de profundidade (0-20, 20-40, 40-60, 60-80 e 80-100 cm) foram coletadas e analisadas para diferentes características físico-químicas do solo. Os resultados mostraram uma variação significativa nos valores de densidade do solo (BD), porosidade do solo, pH, capacidade de troca catiônica (CEC) e condutividade elétrica (CE). Mais DB do solo (1,41 g cm-3) e pH (6,97) do solo foram observados na camada profunda do solo (80-100 cm), enquanto os maiores valores de porosidade (60,6%), CE (0,09 mS cm-1) e CEC (32,9 c mol kg-1) foram refletidos na camada superior do solo (0-20 cm). Da mesma forma, os maiores teores de carbono orgânico do solo (SOC), fósforo total (TP), fósforo disponível (AP), nitrogênio total (TN) e potássio disponível (AK) foram calculados na camada superficial do solo (0-20 cm). Com o aumento do incremento da profundidade do solo, uma tendência decrescente no SOC e na concentração de outros nutrientes foi encontrada, enquanto o potássio total do solo (TK) produziu uma correlação negativa com a profundidade da camada do solo. Todos os resultados produziram a distribuição de SOCs e TNs (estoques) em várias profundidades de solo em padrões de floresta 0 → 20cm> 20 → 40cm> 40 → 60cm ≥ 60 → 80cm ≥ 80 → 100 cm. Além disso, as relações estequiométricas de C, N e P, as relações C / P e N / P, apresentaram valores máximos (66,49 e 5,46) em 0-20 cm, e valores mais baixos (23,78 e 1,91) em solo de 80-100 cm profundidade da camada. Embora a relação C / N fosse estatisticamente semelhante em todo o perfil do solo (0-100 cm). Esses resultados destacaram que os incrementos de profundidade do solo podem ser amplamente atribuídos a flutuações nas propriedades físico-químicas do solo, estoques e estequiometrias do solo. Mais estudos são necessários para tirar conclusões adicionais sobre a dinâmica dos nutrientes, estoques de solo e estequiometria do solo nessas florestas.

Morpho-physiological and phytohormonal changes during the induction of adventitious root development stimulated by exogenous IBA application in Magnolia biondii Pamp / Alterações morfofisiológicas e fito-hormonais durante a indução do desenvolvimento radicular adventício estimulado pela aplicação exógena do AIB em Magnolia biondii Pamp

Magnolia biondii Pamp is an important ornamental tree species widely grown and used as a rootstock in the propagation of different Magnolia varieties. In the current studies, anatomical, physiological and endogenous hormones were studied to check the effect of IBA 750 mg/L on the adventitious rooting and to provide theoretical and technical support for the propagation of Magnolia biondii Pamp through stem cuttings. Two thousand stem cuttings were prepared and divided into two groups i.e., IBA treated cuttings and water control. For the evaluation of antioxidant enzyme activities, and endogenous hormones levels, samples were collected on the day of planting and each 5th day and further steps were carried out in the laboratory according to the protocols and proper precautions. For the anatomical observations, samples were collected on the 13th, 15th, and 17th day for IBA treated cuttings while 21st, 23rd, and 25th day for control. Collected samples were preserved in the FAA solution and further observations were carried out in the laboratory. Anatomical observations showed that it took 13 days for the differentiation of root primordia to the appearance of young adventitious roots in IBA treated cuttings, while it took 21 days to develop primordia in the control. Antioxidant enzyme activities involved in ROS were significantly higher in the IBA treated cuttings compared to control. POD showed a peak on the 13th day before the emergence of roots in IBA treated cuttings while it showed a peak on the 21st day in the control. PPO showed a peak on the 21st day in the IBA treated cuttings while it showed a peak on the 29th day in the control. SOD showed a peak on the 17th day in IBA treated cuttings, while it showed a peak on the 25th day in the control. Exogenous application of IBA enhanced the endogenous IAA and GA3 levels compared to CK, while it reduced the levels of ABA continuously at the time of rooting and then increased gradually. Inclusively, our study suggests that IBA 750 mg/L is efficient for the rooting of Magnolia biondii Pamp cuttings, as it enhanced the process of antioxidant enzyme activities, endogenous hormones levels and reduced the time of root formation which is evident from the anatomical observations.

Magnolia biondii Pamp é uma importante espécie de árvore ornamental muito cultivada e utilizada como porta-enxerto na propagação de diferentes variedades de Magnolia. Nos estudos atuais, hormônios anatômicos, fisiológicos e endógenos foram estudados para verificar o efeito do AIB na dose de 750 mg / L no enraizamento adventício e fornecer suporte teórico e técnico para a propagação de M. biondii Pamp por meio de estacas. Duas mil estacas foram preparadas e divididas em dois grupos, ou seja, tratadas com AIB e controle de água. Para a avaliação das atividades das enzimas antioxidantes e dos níveis de hormônios endógenos, as amostras foram coletadas no dia do plantio e a cada 5 dias, enquanto as demais etapas foram realizadas em laboratório de acordo com os protocolos e os devidos cuidados. Para as observações anatômicas, as amostras foram coletadas no 13º, 15º e 17º dias para estacas tratadas com AIB e no 21º, 23º e 25º dias para o controle. As amostras coletadas foram preservadas em solução FAA, e outras observações foram realizadas em laboratório. Observações anatômicas mostraram a necessidade de 13 dias para a diferenciação dos primórdios radiculares até o aparecimento de raízes adventícias jovens em estacas tratadas com AIB e de 21 dias para o desenvolvimento dos primórdios no controle. As atividades das enzimas antioxidantes envolvidas nas ROS foram significativamente maiores nas estacas tratadas com AIB em comparação com o controle. A POD apresentou pico no 13º dia antes da emergência das raízes nas estacas tratadas com AIB, enquanto no 21º dia apresentou pico no controle. A PPO teve pico no 21º dia nas estacas tratadas com AIB e no 29º dia no controle. A SOD apresentou pico no 17º dia nas estacas tratadas com AIB e no 25º dia no controle. A aplicação exógena de AIB aumentou os níveis endógenos de IAA e GA3 em relação ao controle, enquanto reduziu os níveis de ABA continuamente no momento do enraizamento e, em seguida, aumentou gradativamente. Inclusive, nosso estudo sugere que o AIB na dose de 750 mg / L é eficiente para o enraizamento de estacas de M. biondii Pamp, visto que potencializou o processo de atividades de enzimas antioxidantes e os níveis de hormônios endógenos, além de reduzir o tempo de formação de raízes, o que fica evidente nas observações anatômicas.

Cell-to-Cell Communications of cGAS-STING Pathway in Tumor Immune Microenvironment / 浙江大学学报·医学版

Targeting cGAS-STING pathway is a promising strategy in tumor treatment. The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of the second messenger 2'3'-cGAMP, activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING. Notably, in tumor immune microenvironment, key components of cGAS-STING pathway are transferred among neighboring cells. The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity. The membrane-based system, including extracellular vesicles transport, phagocytosis and membrane fusion transmit dsDNA, cGAMP and activated STING, enhancing the immune surveillance and inflammatory. The membrane proteins, including specific protein channel and intercellular gap junctions, transfer cGAMP and dsDNA, which are crucial to regulate immune responses. And the ligand-receptor interactions for interferons transmission amplifies the anti-tumor response. This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment. We further explore how these mechanisms modulate immunological processes and discuss potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China / 中国当代儿科杂志

OBJECTIVES@#To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China.@*METHODS@#A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.@*RESULTS@#A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance.@*CONCLUSIONS@#This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Risk factors for ketoacidosis in children/adolescents with type 1 diabetes mellitus and establishment of a predictive model / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors for diabetic ketoacidosis (DKA) in children/adolescents with type 1 diabetes mellitus (T1DM) and to establish a model for predicting the risk of DKA.@*METHODS@#A retrospective analysis was performed on 217 children/adolescents with T1DM who were admitted to General Hospital of Ningxia Medical University from January 2018 to December 2021. Among the 217 children/adolescents,169 cases with DKA were included as the DKA group and 48 cases without DKA were included as the non-DKA group. The risk factors for DKA in the children/adolescents with T1DM were analyzed, and a nomogram model was established for predicting the risk of DKA in children/adolescents with T1DM.@*RESULTS@#For the 217 children/adolescents with T1DM, the incidence rate of DKA was 77.9% (169/217). The multivariate logistic regression analysis showed that high levels of random blood glucose, hemoglobin A1c (HbA1c), blood ketone body, and triglyceride on admission were closely associated with the development of DKA in the children/adolescents with T1DM (OR=1.156, 3.2031015, 20.131, and 9.519 respectively; P<0.05). The nomogram prediction model had a C-statistic of 0.95, with a mean absolute error of 0.004 between the risk of DKA predicted by the nomogram model and the actual risk of DKA, indicating that the model had a good overall prediction ability.@*CONCLUSIONS@#High levels of random blood glucose, HbA1c, blood ketone body, and triglyceride on admission are closely associated with the development of DKA in children/adolescents with T1DM, and targeted intervention measures should be developed to reduce the risk of DKA.

Risk factors for delayed bleeding after intestinal polypectomy in children / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical characteristics and risk factors of delayed bleeding after intestinal polypectomy in children, and to provide a theoretical basis for clinical surgical intervention of intestinal polyps.@*METHODS@#A retrospective analysis was conducted on the clinical data of 2 456 children with intestinal polyps who underwent endoscopic high-frequency electrocoagulation loop resection in the Endoscopy Center of Children's Hospital Affiliated to Zhengzhou University from January 2014 to December 2021. According to the presence or absence of delayed bleeding after surgery, they were divided into bleeding group with 79 children and non-bleeding group with 2 377 children. A multivariate logistic regression analysis was used to investigate the risk factors for delayed bleeding. The receiver operating characteristic (ROC) curve was used to investigate the value of various indicators in predicting delayed bleeding.@*RESULTS@#Of all 2 456 children, 79 (3.22%) experienced delayed bleeding, among whom 5 children with severe delayed bleeding underwent emergency colonoscopy for hemostasis and 74 received conservative treatment, and successful hemostasis was achieved for all children. There were significant differences between the bleeding and non-bleeding groups in age, body mass index, constipation rate, location of lesion, time of endoscopic procedure, resection method (P<0.05). Children with a diameter of polyps of 6-10 mm and >20 mm were more likely to develop delayed bleeding after resection (P<0.05). The multivariate logistic regression analysis showed that endoscopic operation time, polyp diameter, and resection method were significantly associated with delayed bleeding (P<0.05). The ROC curve analysis showed that the endoscopic operation time, polyp diameter, and resection method had a good value in predicting delayed bleeding after intestinal polypectomy, with an area under the ROC curve of 0.706, 0.688, and 0.627, respectively.@*CONCLUSIONS@#Endoscopic high-frequency electrocoagulation loop resection has a lower incidence of delayed bleeding in children with intestinal polyps, and the endoscopic operation time, polyp diameter, and resection method are closely associated with the occurrence of postoperative delayed bleeding.

Efficacy of bronchoalveolar lavage combined with prone positioning in children with Mycoplasma pneumoniae pneumonia and atelectasis: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy of bronchoalveolar lavage (BAL) combined with prone positioning in children with Mycoplasma pneumoniae pneumonia (MPP) and atelectasis and its effect on pulmonary function.@*METHODS@#A prospective study was conducted on 94 children with MPP and atelectasis who were hospitalized in Ordos Central Hospital of Inner Mongolia from November 2020 to May 2023. The children were randomly divided into a treatment group and a control group, with 47 children in each group. The children in the treatment group were given conventional treatment, BAL, and prone positioning, and those in the control group were given conventional treatment and BAL. The two groups were compared in terms of fever, pulmonary signs, length of hospital stay, lung recruitment, and improvement in pulmonary function.@*RESULTS@#Compared with the control group, the treatment group had significantly shorter time to improvement in pulmonary signs and length of hospital stay and a significantly higher rate of lung recruitment on day 7 of hospitalization, on the day of discharge, and at 1 week after discharge (P<0.05). Compared with the control group, the treatment group had significantly higher levels of forced vital capacity (FVC) as a percentage of the predicted value, forced expiratory volume (FEV) in 1 second as a percentage of the predicted value, ratio of FEV in 1 second to FVC, forced expiratory flow at 50% of FVC as a percentage of the predicted value, forced expiratory flow at 75% of FVC as a percentage of the predicted value, and maximal mid-expiratory flow as a percentage of the predicted value on the day of discharge and at 1 week after discharge (P<0.05). There was no significant difference in the time for body temperature to return to normal between the two groups (P>0.05).@*CONCLUSIONS@#In the treatment of children with MPP and atelectasis, BAL combined with prone positioning can help to shorten the time to improvement in pulmonary signs and the length of hospital stay and promote lung recruitment and improvement in pulmonary function.

Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics / 中华创伤杂志(英文版)

PURPOSE@#To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.@*METHODS@#This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay.@*RESULTS@#Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.@*CONCLUSIONS@#Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Mannitol inhibits the proliferation of neural stem cell by a p38 mitogen-activated protein kinase-dependent signaling pathway / 中华创伤杂志(英文版)

PURPOSE@#Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.@*METHODS@#C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference.@*RESULTS@#Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.@*CONCLUSIONS@#Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Progress in targeted inhibition of aerobic glycolysis combined with immunotherapy for renal cell carcinoma / 细胞与分子免疫学杂志

Tumor aerobic glycolysis is one of the main features of tumor metabolic reprogramming. This abnormal glycolytic metabolism provides bioenergy and biomaterials for tumor growth and proliferation. It is worth noting that aerobic glycolysis will not only provide biological materials and energy for tumor cells, but also help tumor cells to escape immune surveillance through regulation of immune microenvironment, thereby resisting tumor immunotherapy and promoting tumor progression. Based on the pathogenesis of renal cell carcinoma, this paper describes the characteristics of aerobic glycolysis, the effect of glycolytic metabolism on the immune microenvironment of renal cell carcinoma, the effect of glycolysis inhibitors on the immune microenvironment of renal cell carcinoma, and the prospect of glycolysis inhibitors combined with immune checkpoint inhibitors in the treatment of renal cell carcinoma.

Research progress on mTOR signaling pathway and regulatory T cell nutrition metabolic regulation mechanism / 细胞与分子免疫学杂志

In the tumor microenvironment, metabolic reprogramming can impact metabolic characteristics of T cells, thus inducing immunosuppression to promote tumor immune escape. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in regulating diverse functions of various immune cells. This review mainly focuses on the molecular mechanism of mTOR signaling in regulating cellular energy metabolism process, and the activation status of mTOR signaling under different nutritional environments. In addition, it also summarizes the role of the mTOR signaling in regulatory T cell (Tregs) metabolism and function in current studies, and evaluates the potential of mTOR as a clinical immunotherapeutic target and its current application challenges.