Varying the ratio of Lys: Met through enhancing methionine supplementation improved milk secretion ability through regulating the mRNA expression in bovine mammary epithelial cells under heat stress.

Introduction: The ratio of lysine (Lys) to methionine (Met) with 3.0: 1 is confirmed as the "ideal" profile for milk protein synthesis, but whether this ratio is suitable for milk protein synthesis under HS needs to be further studied. Methods: To evaluate the molecular mechanism by which HS and Lys to Met ratios affect mammary cell functional capacity, an immortalized bovine mammary epithelial cell line (MAC-T) is incubated with 5 doses of Met while maintaining a constant concentration of Lys. The MAC-T cells was treated for 6 h as follow: Lys: Met 3.0: 1 (control 37°C and IPAA 42°C) or treatments under HS (42°C) with different ratios of Lys: Met at 2.0: 1 (LM20), 2.5: 1 (LM25), 3.5: 1 (LM35) and 4.0: 1 (LM40). RNA sequencing was used to assess transcriptome-wide alterations in mRNA abundance. Results: The significant difference between control and other groups was observed base on PCA analysis. A total of 2048 differentially expressed genes (DEGs) were identified in the IPAA group relative to the control group. Similarly, 226, 306, 148, 157 DEGs were detected in the LM20, LM25, LM35 and LM40 groups, respectively, relative to the IPAA group. The relative mRNA abundance of HSPA1A was upregulated and anti-apoptotic genes (BCL2L1 and BCL2) was down-regulated in the IPAA group, compared to the control group (p < 0.05). Compared with the IPAA group, the relative mRNA abundance of anti-apoptotic genes and casein genes (CSN1S2 and CSN2) was up-regulated in the LM25 group (p < 0.05). The DEGs between LM25 and IPAA groups were associated with the negative regulation of transcription RNA polymerase II promoter in response to stress (GO: 0051085, DEGs of BAG3, DNAJB1, HSPA1A) as well as the mTOR signaling pathway (ko04150, DEGs of ATP6V1C2, WNT11, WNT3A, and WNT9A). Several DEGs involved in amino acids metabolism (AFMID, HYKK, NOS3, RIMKLB) and glycolysis/gluconeogenesis (AFMID and MGAT5B) were up-regulated while DEGs involved in lipolysis and beta-oxidation catabolic processes (ALOX12 and ALOX12B) were down-regulated. Conclusion: These results suggested that increasing Met supply (Lys: Met at 2.5: 1) may help mammary gland cells resist HS-induced cell damage, while possibly maintaining lactation capacity through regulation of gene expression.

Association of serum interleukin-2 with severity and prognosis in hospitalized patients with community-acquired pneumonia: a prospective cohort study.

The prior studies have shown that interleukin-2 (IL-2) exerts important roles in the pathological and physiological processes of lung diseases. However, the role of IL-2 in community-acquired pneumonia (CAP) is still uncertain. Through a prospective cohort study, our research will explore the correlations between serum IL-2 levels and the severity and prognosis in CAP patients. There were 267 CAP patients included. Blood samples were obtained. Serum IL-2 were tested by enzyme-linked immunosorbent assay (ELISA). Demographic traits and clinical characteristics were extracted. Serum IL-2 were gradually elevated with increasing severity scores in CAP patients. Correlation analyses revealed that serum IL-2 were connected with physiological parameters including liver and renal function in CAP patients. According to a logistic regression analysis, serum IL-2 were positively correlated with CAP severity scores. We also tracked the prognostic outcomes of CAP patients. The increased risks of adversely prognostic outcomes, including mechanical ventilation, vasoactive agent usage, ICU admission, death, and longer hospital length, were associated with higher levels of IL-2 at admission. Serum IL-2 at admission were positively associated with severe conditions and poor prognosis among CAP patients, indicated that IL-2 may involve in the initiation and development of CAP. As a result, serum IL-2 may be an available biomarker to guide clinicians in assessing the severity and determining the prognosis of CAP.

Esophageal squamous cell carcinoma metastases to kidney and renal hilar lymph nodes through epithelial-mesenchymal transition: a case report and literature review.

BACKGROUND: Esophageal cancer (EC) metastasized to the kidney is extremely rare clinically. Here, we present a case of metachronous renal metastasis of esophageal squamous cell carcinoma (ESCC) through epithelial-mesenchymal transition (EMT). CASE PRESENTATION: A 60-year-old patient, male, complained of left waist pain for 5 days, 11 months after radical esophagectomy. Laboratory tests revealed haematuria. Both CT and PET-CT scan showed retroperitoneal lymph nodes and left renal masses. Subsequently the patient received a left nephrectomy and lymph nodes resection, and squamous cell carcinoma of kidney and renal hilar lymph nodes was diagnosed, combined with morphology, medical history and immunophenotype, it was presumed to be metastasis of ESCC through the EMT pathway. CONCLUSIONS: The renal metastasis of squamous cell carcinoma should be considered in patients with history of EC, although this is very rare. Histopathological examination combined with immunochemical detection is helpful in differential diagnosis.

Pseudohyperkalemia in pediatric patients with newly diagnosed hematological malignancies.

Patients with newly diagnosed hematological malignancies often present with a considerable cellular burden, leading to complications including hyperkalemia. However, pseudohyperkalemia, arising from in vitro cell lysis, can pose challenges in clinical practice. Although pseudohyperkalemia is frequently reported in adult hematological malignancies, its occurrence in pediatric patients is underreported, and its incidence in this demographic remains unclear. We retrospectively reviewed the medical records of pediatric patients who received a new diagnosis of hematological malignancies from 2011 to 2022 at Taichung Veterans General Hospital. Hyperkalemia was defined by a serum or plasma potassium level exceeding 5.5 mEq/L. Pseudohyperkalemia was defined by 1) a potassium decrease of over 1 mEq/L in within 4 h without intervention or 2) the absence of electrocardiography changes indicative of hyperkalemia. Cases with apparent red blood cell hemolysis were excluded. A total of 157 pediatric patients with a new diagnosis of hematological malignancies were included, 14 of whom exhibited hyperkalemia. Among these 14 cases, 7 cases (4.5%) were of pseudohyperkalemia. This rate increased to 21.2% in patients with initial hyperleukocytosis. Pseudohyperkalemia was associated with a higher initial white blood cell count and lower serum sodium level. All episodes of pseudohyperkalemia occurred in the pediatric emergency department, where samples were obtained as plasma, whereas all true hyperkalemia cases were observed in the ordinary ward or intensive care unit, where samples were obtained as serum. Timely recognition of pseudohyperkalemia is crucial to avoiding unnecessary potassium-lowering interventions in pediatric patients with newly diagnosed hematological malignancies.

Serum SOD1 level predicts the severity and prognosis of community-acquired pneumonia patients.

BACKGROUND: Superoxide dismutase 1 (SOD1) is one of the most important participants of antioxidant enzyme system in biological system. Previous studies have found that SOD1 is associated with many inflammatory diseases. The goal of this study was to assess the associations of serum SOD1 with the severity and prognosis in community-acquired pneumonia (CAP) patients by a prospective cohort study. METHODS: CAP patients were enrolled from the Second Affiliated Hospital of Anhui Medical University. Peripheral blood samples were gathered. The level of serum SOD1 was detected through enzyme linked immunosorbent assay (ELISA). Clinical characteristics and demographic information were analyzed. RESULTS: The level of serum SOD1 was gradually upregulated with elevated CAP severity scores. Spearman correlation coefficient or Pearson rank correlation analyses indicated that serum SOD1 was strongly connected with many clinical parameters among CAP patients. Further linear and logistic regression analyses found that the level of serum SOD1 was positively associated with CRB-65, CURB-65, SMART-COP, and CURXO scores among CAP patients. Moreover, serum higher SOD1 at admission substantially increased the risks of ICU admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stays during hospitalization. Serum SOD1 level combination with CAP severity scores elevated the predictive abilities for severity and death compared with alone serum SOD1 and CAP severity scores in CAP patients during hospitalization. CONCLUSION: The level of serum SOD1 is positively associated with the severity and poor prognosis in CAP patients, suggesting that SOD1 is implicated in the initiation and progression of CAP. Serum SOD1 may be regarded as a biomarker to appraise the severity and prognosis for CAP patients.

Effects of Foliar Spraying of Dicarboxylicdimethylammonium Chloride on Cadmium and Arsenic Accumulation in Rice Grains.

A field experiment with double cropping rice was carried out to study the foliar application effects of dicarboxylicdimethylammonium chloride (DDAC) on cadmium (Cd) and arsenic (As) accumulation in rice grains. The results showed that the spraying of DDAC could significantly reduce the accumulation of Cd and As in rice grains. The highest reductions in Cd and As content were observed when 1.5 mmol L-1 DDAC was sprayed, with 49.1% and 27.4% reductions in Cd and As content in early rice grains and 56.5% and 28.1% reductions in Cd and As content in late rice grains, respectively. In addition, the content of calcium (Ca) in rice grains increased significantly after DDAC foliar application, which was also conducive to the synthesis of amino acids such as glutamate (Glu), glycine (Gly) and cysteine (Cys) in rice grains. The results indicated that the foliar spraying of DDAC can inhibit the absorption, transport, accumulation and toxicity of Cd and As in rice grains by increasing amino acid synthesis and regulating the absorption and transport of essential elements.

[Climate change affects plant aboveground biomass by regulating the growth periods in alpine grasslands of the Tibetan Plateau, China]. / 气候变化通过调控青藏高原高寒草原植物生育期影响地上生物量积累.

Climate change significantly affects plant biomass and phenological occurrence time in alpine grasslands of Tibetan Plateau. The changes in phenological periods are closely related to the length of vegetative and reproductive growth periods, which may further affect aboveground biomass accumulation. In this study, based on fixed-point observations of plant biomass and phenology as well as the corresponding climatic data from 1997 to 2020 in the alpine grasslands of Tibetan Plateau, we used statistical methods such as ordinary linear regression and piecewise structural equation model to explore the characteristics of interannual climate change in the study area, the variation trends of plant biomass and phenological periods, and the correlations between biomass and phenological and climatic factors. The results showed that mean annual temperature and annual precipitation in the study area increased significantly from 1997 to 2020, suggesting a clear "warm-wet" trend. Aboveground biomass and relative biomass of Stipa sareptana var. krylovii (the dominant species) decreased significantly. However, absolute and relative biomass of subdominant species (Kobresia humilis) increased significantly, indicating that the dominance of K. humilis increased. The warm-wet climates enhanced aboveground biomass accumulation of K. humilis by extending the period of reproductive growth. Mean annual temperature and annual precipitation decreased aboveground biomass of S. sareptana by shortening the length of vegetative growth period. In a word, the warmer and wetter climate significantly affected aboveground biomass accumulation by regulating the changes in the phenological period, and the interspecific difference in their response resulted in a larger change in community composition. This study area may show a trend from alpine grassland to alpine meadow, and thus further works are urgently needed.

GLUT1 mediates bronchial epithelial E-cadherin disruption in TDI-induced steroid-insensitive asthma.

OBJECTIVE: Down-regulation of bronchial epithelial E-cadherin is an important of feature of severe asthma, including steroid-insensitive asthma. Yet, the mechanisms involved in E-cadherin disruption are not fully understood. This study was aimed to investigate the role of glucose transporter 1 (GLUT1) in dysregulation of E-cadherin in toluene diisocyanate (TDI)-induced steroid-insensitive asthma. METHODS: A murine model of steroid-insensitive asthma was established by TDI sensitization and aerosol inhalation. Selective GLUT1 antagonists WZB117 and BAY876 were given to BALB/c mice after airway challenge. In vitro, primary human bronchial epithelial cells (HBECs) cultured in an airway-liquid interface (ALI) were exposed to TDI. RESULTS: TDI exposure markedly up-regulated GLUT1 in murine lungs and HBECs. Pharmacological inhibition of GLUT1 with BAY876 decreased airway hyperresponsiveness, neutrophil and eosinophil accumulation, as well as type 2 inflammation in vivo. Besides, the TDI-induced down-regulated expression of full-length E-cadherin was also partly recovered, accompanied by inhibited secretion of soluble E-cadherin (sE-cadherin). WZB117 also exhibited mild therapeutic effects, though not significant. In vitro, treatment with GLUT1 inhibitor relieved the TDI-induced disruption of E-cadherin in HBECs. CONCLUSIONS: Taken together, our data demonstrated that GLUT1 modulates bronchial epithelial E-cadherin dysfunction production in TDI-induced steroid-insensitive asthma.

A novel "on-off-on" electrochemiluminescence aptasensor based on resonance energy transfer as signal amplification strategy for ultrasensitive detection of sulfadiazine in different samples.

The misuse of antibiotics may contaminate the environment and cause harm to human health. Therefore, rapid and accurate detection of antibiotics is essential. In this study, a novel electrochemiluminescence resonance energy transfer (ECL-RET) pair was designed using a new ECL emitter (CPM, Ce-TBAPy) as the donor and Co-MOF@AuPt as the acceptor. Moreover, a highly sensitive and specific "on-off-on" ECL aptasensor was constructed for detecting sulfadiazine (SDZ). The aptasensor exhibited a broad linear range (from 10.0 fg mL-1 to 100 ng mL-1) for the SDZ concentration, with limit of detection and limit of quantification values of 1.14 fg mL-1and 3.75 fg mL-1, respectively. The aptasensor achieved good results in spiking experiments with milk and egg samples, and successfully quantified SDZ in fish meal quality control sample. The prepared aptasensor presents great potential for food and environmental safety by detecting antibiotics.

Intravenous thrombolysis versus dual antiplatelet therapy for patients with acute minor ischaemic stroke: a systematic review and meta-analysis.

Background and purpose: The efficacy of intravenous thrombolysis (IVT) in patients with acute minor ischaemic stroke (AMIS) remains unclear. We performed a meta-analysis to compare the efficacy and safety of IVT and dual antiplatelet therapy (DAPT) in patients with AMIS. Methods: The Embase, Cochrane Library, PubMed, and Web of Science databases were searched up to 10 October, 2023. Prospective and retrospective studies comparing the clinical outcomes of IVT and DAPT were included. Odds ratios (ORs) and 95% confidence intervals (CIs) for early neurological deterioration (END), excellent and favourable functional outcomes, recurrent ischaemic stroke at 3 months, mortality at 3 months, and symptomatic intracranial haemorrhage (ICH) were pooled using a random-effects model. Results: Of the five included studies, 6,340 patients were included. In patients with AMIS, IVT was not significantly associated with excellent and favourable functional outcomes, recurrent ischaemic stroke, or all-cause mortality at 3 months compared to early DAPT. However, a higher risk of symptomatic ICH (OR, 9.31; 95% CI, 3.39-25.57) and END (OR, 2.75; 95% CI, 1.76-4.30) were observed with IVT. Conclusion: This meta-analysis indicated that IVT was not superior to DAPT in patients with AMIS, especially in those with nondisabling AIS. However, these findings should be interpreted with caution and have some limitations. Further, well-designed randomised controlled trials are warranted.

Benzo[a]pyrene evokes epithelial-mesenchymal transition and pulmonary fibrosis through AhR-mediated Nrf2-p62 signaling.

Benzo[a]pyrene (BaP) and its metabolic end product benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide (BPDE), are known toxic environmental pollutants. This study aimed to analyze whether sub-chronic BPDE exposure initiated pulmonary fibrosis and the potential mechanisms. In this work, male C57BL6/J mice were exposed to BPDE by dynamic inhalation exposure for 8 weeks. Our results indicated that sub-chronic BPDE exposure evoked pulmonary fibrosis and epithelial-mesenchymal transition (EMT) in mice. Both in vivo and in vitro, BPDE exposure promoted nuclear translocation of Snail. Further experiments indicated that nuclear factor erythroid 2-related factor 2 (Nrf2) and p62 were upregulated in BPDE-exposed alveolar epithelial cells. Moreover, Nrf2 siRNA transfection evidently attenuated BPDE-induced p62 upregulation. Besides, p62 shRNA inhibited BPDE-incurred Snail nuclear translocation and EMT. Mechanically, BPDE facilitated physical interaction between p62 and Snail in the nucleus, then repressed Snail protein degradation by p62-dependent autophagy-lysosome pathway, and finally upregulated transcriptional activity of Snail. Additionally, aryl hydrocarbon receptor (AhR) was activated in BPDE-treated alveolar epithelial cells. Dual-luciferase assay indicated activating AhR could bind to Nrf2 gene promoter. Moreover, pretreatment with CH223191 or α-naphthoflavone (α-NF), AhR antagonists, inhibited BPDE-activated Nrf2-p62 signaling, and alleviated BPDE-induced EMT and pulmonary fibrosis in mice. Taken together, AhR-mediated Nrf2-p62 signaling contributes to BaP-induced EMT and pulmonary fibrosis.

Associations of the Serum KL-6 with Severity and Prognosis in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

BACKGROUND: As a biomarker of alveolar-capillary basement membrane injury, Krebs von den Lungen-6 (KL-6) is involved in the occurrence and development of pulmonary diseases. However, the role of the KL-6 in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has yet to be elucidated. This prospective study was designed to clarify the associations of the serum KL-6 with the severity and prognosis in patients with AECOPD. METHODS: This study enrolled 199 eligible AECOPD patients. Demographic data and clinical characteristics were recorded. Follow-up was tracked to evaluate acute exacerbation and death. The serum KL-6 concentration was measured via an enzyme-linked immunosorbent assay. RESULTS: Serum KL-6 level at admission was higher in AECOPD patients than in control subjects. The serum KL-6 concentration gradually elevated with increasing severity of AECOPD. Pearson and Spearman analyses revealed that the serum KL-6 concentration was positively correlated with the severity score, monocyte count and concentrations of C-reactive protein, interleukin-6, uric acid, and lactate dehydrogenase in AECOPD patients during hospitalization. A statistical analysis of long-term follow-up data showed that elevated KL-6 level at admission was associated with longer hospital stays, an increased risk of future frequent acute exacerbations, and increased severity of exacerbation in COPD patients. CONCLUSION: Serum KL-6 level at admission is positively correlated with increased disease severity, prolonged hospital stay and increased risk of future acute exacerbations in COPD patients. There are positive dose-response associations of elevated serum KL-6 with severity and poor prognosis in COPD patients. The serum KL-6 concentration could be a novel diagnostic and prognostic biomarker in AECOPD patients.

Pretreatment of wastepaper with an aqueous solution of amino acid-derived ionic liquid for biochar production as adsorbent.

The carbonization of lignocellulosic biomass with ionic liquids (ILs) are considered as an advantageous approach for the preparation of carbonaceous materials. The commonly used imidazolium and pyridinium based ILs have drawbacks such as toxicity, resistance to biodegradation, high cost and viscosity. These issues can be mitigated by diluting ILs with water, although excessive water content above 1 wt% can reduce the solubility of biomass. This research aims to investigate the potential of pretreating wastepaper with a "fully green" ILs, amino acid-based IL with high water content, followed by pyrolysis without IL, in enhancing the properties of biochar. For this purpose, the paper was treated with an aqueous solution of IL cysteine nitrate ([Cys][NO3]), and the IL was not involved in the pyrolysis process to prevent the formation of secondary gaseous pollutants. The findings revealed that the hemicellulose and mineral filler in the paper were eliminated during pretreatment, leading to higher carbon content but lower oxygen content. As a result, the biochar exhibited micropores of 0.42 cm3g-1 and a specific surface area of 1011.21 m2 g-1. The biochar demonstrated high adsorption capacities for Cd2+, enrofloxacin, bisphenol A, ciprofloxacin, and tetracycline, with values of 45.20 mg g-1, 49.82 mg g-1, 49.90 mg g-1, 49.88 mg g-1, and 49.65 mg g-1, respectively. The proposed mechanism for the adsorption of enrofloxacin by the biochar primarily involves physical adsorption such as pore filling and electrostatic interactions, along with chemical adsorption facilitated by graphitic nitrogen.

Design, synthesis, and biological evaluation of new bis-benzylisoquinoline-based analogues as potential neuromuscular blocking agents.

Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure-activity and configuration-activity relationships of these derivatives and 29a's binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.

Relationships among Sleep Time, Physical Activity Time, Screen Time, and Nutrition Literacy of Adolescents: A Cross-Sectional Study in Chongqing, China.

Background: Unhealthy lifestyles among adolescents are reaching alarming levels and have become a major public health problem. This study aimed to assess the relationship between sleep time, physical activity (PA) time, screen time (ST), and nutritional literacy (NL). Methods: This cross-sectional online study involving adolescents aged 10-18 years was conducted in September 2020 in 239 schools in Chongqing, China. NL was measured using the "Nutrition Literacy Scale for middle school students in Chongqing (CM-NLS)". According to the recommended by the Chinese dietary guidelines (2022), we divided the sleep time of junior high school students into <9 h and ≥9 h, high school students into <8 h and ≥8 h, divided the workdays into weekend PA time < 1 h and ≥1 h, and divided the workdays into weekend ST < 2 h and ≥2 h. The multinomial logistic regression model was used to examine the association. Results: A total of 18,660 adolescents (50.2% males) were included. The proportion of participants that were junior high school students and attended boarding schools was 57.2% and 65.3%, respectively. Compared with senior high school students, junior high school students had a higher level of NL. Whether on workdays or weekends, participants with sleep time ≥ 8/9 h, PA time ≥ 1 h, and ST < 2 h per day had higher levels of NL. On weekdays, participants who met the sleep time ≥ 8 h/9 h (OR = 1.48, 95% CI: 1.36, 1.62) and PA time ≥ 1 h (OR = 1.69, 95% CI: 1.59, 1.81) had higher reporting of NL levels. Conclusions: Sleep time, PA time, and ST were positively correlated with NL among adolescents, especially junior high school students.

Thermally Activated Delayed Fluorescence with Nanosecond Emission Lifetimes and Minor Concentration Quenching: Achieving High-Performance Nondoped and Doped Blue OLEDs.

Simultaneously achieving a high photoluminescence quantum yield (PLQY), ultrashort exciton lifetime, and suppressed concentration quenching in thermally activated delayed fluorescence (TADF) materials is desirable yet challenging. Here, a novel acceptor-donor-acceptor type TADF emitter, namely, 2BO-sQA, wherein two oxygen-bridged triarylboron (BO) acceptors are arranged with cofacial alignment and positioned nearly orthogonal to the rigid dispirofluorene-quinolinoacridine (sQA) donor is reported. This molecular design enables the compound to achieve highly efficient (PLQYs up to 99%) and short-lived (nanosecond-scale) blue TADF with effectively suppressed concentration quenching in films. Consequently, the doped organic light-emitting diodes (OLEDs) base on 2BO-sQA achieve exceptional electroluminescence performance across a broad range of doping concentrations, maintaining maximum external quantum efficiencies (EQEs) at over 30% for doping concentrations ranging from 10 to 70 wt%. Remarkably, the nondoped blue OLED achieves a record-high maximum EQE of 26.6% with a small efficiency roll-off of 14.0% at 1000 candelas per square meter. By using 2BO-sQA as the sensitizer for the multiresonance TADF emitter ν-DABNA, TADF-sensitized fluorescence OLEDs achieve high-efficiency deep-blue emission. These results demonstrate the feasibility of this molecular design in developing TADF emitters with high efficiency, ultrashort exciton lifetime, and minimal concentration quenching.

Efficient regulation of cadmium accumulation by carboxymethylammonium chloride in rice: Correlation analysis and expression of transporter gene OsGLR3.

The mechanism of carboxymethylammonium chloride (CC) regulating cadmium (Cd) accumulation in rice was studied in field and hydroponic experiments. Field experiments showed that 0.2-1.2 mmol L-1 CC spraying effectively reduced Cd accumulation by 44 %-77 % in early rice grains and 39 %-78 % in late rice grains, significantly increased calcium (Ca) content and amino acids content in grains, as well as alleviated Cd-induced oxidative damage in leaves. Hydroponic experiments further verified the inhibition effect of CC on Cd accumulation. 1.2 mmol L-1 CC made the highest decrease of Cd content in shoots and roots of hydroponic seedlings by 45 % and 53 %, respectively. Exogenous CC significantly increased glutamate (Glu), glycine (Gly) and glutathione (GSH) content, and improved the activities of catalase (CAT) and superoxide dismutase (SOD) by 41-131 % and 11-121 % in shoots of hydroponic seedlings, respectively. Exogenous CC also increased the relative expression of OsGLR3.1-3.5 in the shoots and roots of hydroponic seedlings. The quantum computational chemistry was used to clarify that the Gly radical provided by CC could form various complexes with Cd through carboxyl oxygen atoms. These results showed that exogenous application of CC improved the tolerance to Cd by enhancing the antioxidant capacity; inhibited the absorption, transport and accumulation of Cd in rice by (1) promoting chelation, (2) increasing the GLRs activity through upregulating the content of Glu, Gly, as well as the expression of OsGLR3.1-3.5.

Dynamically changed HSP70 after reperfusion following cerebral infarction in human and rats: correlation with p38 MAPK.

We aimed to clarify the correlation between dynamic change of blood HSP70 and the prognosis of thrombolysis in human and rats, so as to explain the neuroprotection and early warning role of HSP70 in cerebral ischemia-reperfusion. Forty-two patients with acute ischemic stroke were divided into two groups according to the time from onset to thrombolytic therapy: 0 h-3 h (27 patients) and 3-4.5 h group (15 patients). The level of HSP70 in serum before and after thrombolysis was detected by ELISA. Furthermore, a rat model was also used to mimic the ischemic stroke and reperfusion. Peripheral blood of rat samples was collected to detect the level of HSP70 using Elisa. Several signal proteins from MAPK signaling pathway including JNK, p38, ERK (p42/44) were detected at different time points by Western blot of brain tissue. Patients who underwent thrombolytic therapy within 0-3 h had the highest HSP70 level at 1 h after thrombolysis. The higher HSP70 after thrombolysis, the better the patient prognosis. NIHSS scores showed HSP70 was positively correlated with cerebral ischemia. The levels of ERK family (p42/44 MAPK) and p-JNK were decreased gradually along with the time suffering cerebral ischemia. P-ERK, JNK, p-p38 had dynamic changes with increased ischemic time in the middle cerebral artery occlusion model. Dynamic change of HSP70 level in blood may be a biological index that reflects the functional condition of cell survival for cerebral ischemia and estimating the prognostic conditions. Importantly, HSP70 levels in blood were positively correlated with the p38 MAPK pathway in brain tissue.

CacyBP promotes the development of lung adenocarcinoma by regulating OTUD5.

Lung cancer is the most common and lethal malignancy, with lung adenocarcinoma accounting for approximately 40% of all cases. Despite some progress in understanding the pathogenesis of this disease and developing new therapeutic approaches, the current treatments for lung adenocarcinoma remain ineffective due to factors such as high tumour heterogeneity and drug resistance. Therefore, there is an urgent need to identify novel therapeutic targets. CacyBP can regulate a variety of physiological processes by binding to different proteins, but its function in lung adenocarcinoma is unknown. Here, we show that CacyBP is highly expressed in lung adenocarcinoma tissues, and high CacyBP expression correlates with poorer patient survival. Moreover, overexpression of CacyBP promoted the proliferation, migration and invasion of lung adenocarcinoma cell lines. Further mechanistic studies revealed that CacyBP interacts with the tumour suppressor OTUD5, enhances the ubiquitination and proteasomal degradation of OTUD5, and regulates tumorigenesis via OTUD5. In conclusion, our study reveals a novel mechanism by which CacyBP promotes tumorigenesis by increasing the ubiquitination level and proteasome-dependent degradation of OTUD5, providing a potential target for the treatment of lung adenocarcinoma.

Efficacy and safety of mesenchymal stem cell therapy for ovarian ageing in a mouse model.

BACKGROUND: Ovarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified. METHODS: Two common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects. The safety of the treatment was further evaluated, and RNA sequencing was performed to explore the underlying mechanisms involved. RESULTS: After orthotopic transplantation of MSCs into the ovary, the oestrous cycle, ovarian weight, number and proportion of primary follicles, granulosa cell proliferation, and angiogenesis were improved. The effects of AD-MSCs were superior to those of UC-MSCs in several indices, such as post-transplant granulosa cell proliferation, ovarian weight and angiogenesis. Moreover, the tumorigenesis, acute toxicity, immunogenicity and biodistribution of MSCs were evaluated, and both AD-MSCs and UC-MSCs were found to possess high safety profiles. Through RNA sequencing analysis, enhancement of the MAPK cascade was observed, and long-term effects were mainly linked to the activation of immune function. CONCLUSIONS: Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.