Aggressive treatment may be needed for idiopathic membranous nephropathy with focal segmental glomerulosclerosis lesions.

OBJECTIVE: The purpose of this study was to analyze the clinical, pathological, prognostic features and treatment response of the coexistence of focal segmental glomerulosclerosis lesions with idiopathic membranous nephropathy. METHODS: This is a two-center retrospective cohort study. Patients of idiopathic membranous nephropathy were enrolled and divided into two groups with or without focal segmental glomerulosclerosis lesions according to the renal biopsy. Laboratory data and pathological manifestation were compared. Renal phospholipase A2 receptor was detected by immunofluorescence. During the follow-up, the effects of different therapies and renal function were estimated. RESULTS: A total of 236 patients were finally enrolled in this study, of which 60 and 176 idiopathic membranous nephropathy patients were enrolled in the FSGS+ and FSGS- groups, respectively. The FSGS+ group showed a higher percentage of hypertension history (38.3 vs. 20.0%, p=0.004), with a significantly higher level of systolic pressure [137 (120, 160) mmHg vs. 130 (120, 140) mmHg, p=0.009]. Main laboratory findings, including serial albumin (20.4±7.8 g/L vs. 24.5±6.7 g/L, p<0.001), 24-h proteinuria [5.61 (3.10, 7.87) g/day vs. 3.82 (2.31, 5.79) g/day, p=0.002], serial creatinine [80.8 (65.8, 97.9) µmol/L vs. 72.0 (58.7, 84.9) µmol/L, p=0.003], and estimated glomerular filtration rate [86 (66, 101) mL/min/1.73 m2 vs. 95 (81, 108) mL/min/1.73 m2, p=0.007] showed significant differences between the two groups. Pathologically, patients with focal segmental glomerulosclerosis lesions appeared with a higher percentage of crescents, a more severe degree of interstitial fibrosis, and a higher level of membranous nephropathy stage. Renal phospholipase A2 receptor showed a relatively lower positive rate of only 75.0% in the FSGS+ group in comparison with the positive rate of 90.3% in the FSGS- group (p=0.031). The prognosis was generally similar between the two groups. Among patients who were given non-immunosuppression treatment, those with focal segmental glomerulosclerosis lesions took a relatively longer period of time to achieve complete remission (29.3±7.0 m vs. 15.4±8.9 m, p=0.025) and experienced a higher rate of renal function deterioration (37.5 vs. 5.4%, p=0.033) compared with the other ones. While among those receiving immunosuppression treatment, both groups received similar remission rates. CONCLUSION: Compared with FSGS- group, idiopathic membranous nephropathy with focal segmental glomerulosclerosis lesions represented more severe nephrotic syndrome and worse renal function. In view of the renal function decline during the follow-up, more aggressive treatment with the use of immunosuppressants should be considered for idiopathic membranous nephropathy patients with focal segmental glomerulosclerosis lesions.

Identification of early coagulation changes associated with survival outcomes post severe burns from multiple perspectives.

Coagulation alterations manifest early after severe burns and are closely linked to mortality outcomes. Nevertheless, the precise characterization of coagulation changes associated with early mortality remains elusive. We examined alterations in indicators linked to mortality outcomes at both the transcriptomic and clinical characteristic levels. At the transcriptomic level, we pinpointed 28 differentially expressed coagulation-related genes (DECRGs) following burn injuries and endeavored to validate their causal relationships through Mendelian randomization. DECRGs tied to survival exhibit a significant association with neutrophil function, wherein the expression of CYP4F2 and P2RX1 serves as robust predictors of fatal outcomes. In terms of clinical indicators, early levels of D-dimer and alterations in serum calcium show a strong correlation with mortality outcomes. Coagulation depletion and fibrinolytic activation, stemming from the hyperactivation of coagulation pathways post-severe burns, are strongly linked to patient mortality. Monitoring these early coagulation markers with predictive value can effectively identify individuals necessitating priority critical care.

Predictive value of the domain specific PLA2R antibodies for clinical remission in patients with primary membranous nephropathy: A retrospective study.

BACKGROUND: M-type phospholipase A2 receptor (PLA2R) is a major auto-antigen of primary membranous nephropathy(PMN). Anti-PLA2R antibody levels are closely associated with disease severity and therapeutic effectiveness. Analysis of PLA2R antigen epitope reactivity may have a greater predictive value for remission compared with total PLA2R-antibody level. This study aims to elucidate the relationship between domain-specific antibody levels and clinical outcomes of PMN. METHODS: This retrospective analysis included 87 patients with PLA2R-associated PMN. Among them, 40 and 47 were treated with rituximab (RTX) and cyclophosphamide (CTX) regimen, respectively. The quantitative detection of -immunoglobulin G (IgG)/-IgG4 targeting PLA2R and its epitope levels in the serum of patients with PMN were obtained through time-resolved fluorescence immunoassays and served as biomarkers in evaluating the treatment effectiveness. A predictive PMN remission possibility nomogram was developed using multivariate logistic regression analysis. Discrimination in the prediction model was assessed using the area under the receiver operating characteristic curve (AUC-ROC).Bootstrap ROC was used to evaluate the performance of the prediction model. RESULTS: After a 6-month treatment period, the remission rates of proteinuria, including complete remission and partial remission in the RTX and CTX groups, were 70% and 70.21% (P = 0.983), respectively. However, there was a significant difference in immunological remission in the PLA2R-IgG4 between the RTX and CTX groups (21.43% vs. 61.90%, P = 0.019). Furthermore, we found differences in PLA2R-CysR-IgG4(P = 0.030), PLA2R-CTLD1-IgG4(P = 0.005), PLA2R-CTLD678-IgG4(P = 0.003), and epitope spreading (P = 0.023) between responders and non-responders in the CTX group. Multivariate logistic analysis showed that higher levels of urinary protein (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.26-0.95; P = 0.035) and higher levels of PLA2R-CTLD1-IgG4 (OR, 0.79; 95%CI,0.62-0.99; P = 0.041) were independent risk factors for early remission. A multivariate model for estimating the possibility of early remission in patients with PMN is presented as a nomogram. The AUC-ROC of our model was 0.721 (95%CI, 0.601-0.840), in consistency with the results obtained with internal validation, for which the AUC-ROC was 0.711 (95%CI, 0.587-0.824), thus, demonstrating robustness. CONCLUSIONS: Cyclophosphamide can induce immunological remission earlier than rituximab at the span of 6 months. The PLA2R-CTLD1-IgG4 has a better predict value than total PLA2R-IgG for remission of proteinuria at the 6th month.

A grape-supplemented diet prevented ultraviolet (UV) radiation-induced cataract by regulating Nrf2 and XIAP pathways.

The purpose of this study is to investigate if grape consumption, in the form of grape powder (GP), could protect against ultraviolet (UV)-induced cataract. Mice were fed with the regular diet, sugar placebo diet, or a grape diet (regular diet supplemented with 5%, 10%, and 15% GP) for 3 months. The mice were then exposed to UV radiation to induce cataract. The results showed that the GP diet dose-dependently inhibited UV-induced cataract and preserved glutathione pools. Interestingly, UV-induced Nrf2 activation was abolished in the groups on the GP diet, suggesting GP consumption may improve redox homeostasis in the lens, making Nrf2 activation unnecessary. For molecular target prediction, a total of 471 proteins regulated by GP were identified using Agilent Literature Search (ALS) software. Among these targets, the X-linked inhibitor of apoptosis (XIAP) was correlated with all of the main active ingredients of GP, including resveratrol, catechin, quercetin, and anthocyanins. Our data confirmed that GP prevented UV-induced suppression of XIAP, indicating that XIAP might be one of the critical molecular targets of GP. In conclusion, this study demonstrated that GP protected the lens from UV-induced cataract development in mice. The protective effects of GP may be attributed to its ability to improve redox homeostasis and activate the XIAP-mediated antiapoptotic pathway.

Effect of early mobilization on the development of pneumonia in patients with traumatic brain injury in the neurosurgical intensive care unit: A historical controls study.

BACKGROUND: Pneumonia has a high incidence in traumatic brain injury (TBI) patients and lacks effective treatments. Early mobilization (EM) may be a potentially effective treatment. AIM: To explore the impact of EM on TBI-related pneumonia in the neurosurgical intensive care unit (NICU). METHOD: This study was a historical control study. 100 TBI patients who received EM intervention were prospectively included as the experimental group (EM cohort), and 250 TBI patients were retrospectively included as the control group. The propensity score matching (PSM) method was employed to balance baseline and minimize potential bias. The relationship between EM and TBI-related pneumonia was investigated by univariate and multivariate logistic regression, then further determined by subgroup analysis. The influence of other variables was excluded by interaction analyses. Finally, the effect of EM on the prognosis of TBI patients was analysed by comparing the Glasgow Coma Scale (GCS) and the hospital stay. RESULTS: After screening, 86 patients were included in the EM cohort and 199 patients were included in the control cohort. There were obvious differences between the two cohorts at baseline, and these differences were eliminated after PSM, when the incidence of pneumonia was significantly lower in the EM cohort than in the control cohort (35.0% vs. 61.9%, p < .001). Multivariate logistic regression showed that EM was an independent risk factor for TBI-related pneumonia and was significantly associated with a decreased incidence of pneumonia. This correlation was present in most subgroups and was not affected by other variables (p for interaction >.05). Patients in the EM cohort had shorter length of ICU stay (6 vs. 7 days, p = .017) and higher GCS at discharge (12 vs. 11, p = .010). CONCLUSION: EM is a safe and effective treatment for TBI patients in NICU, which can reduce the incidence of pneumonia, help to improve prognosis and shorten the length of ICU stay. RELEVANCE TO CLINICAL PRACTICE: Although the utilization rate of EM is low in TBI patients for various reasons, EM is still an effective method to prevent complications. Our study confirms that a scientific and detailed EM strategy can effectively reduce the incidence of pneumonia while ensuring the safety of TBI patients, which is worthy of further research and clinical application.

Clinicopathological characteristics of placental chorioangioma: A clinicopathological study of 30 cases.

OBJECTIVE: The objective is to explore clinicopathological characteristics, diagnosis, differential diagnoses, treatment, and prognoses of placental chorioangioma (PCA). MATERIALS AND METHODS: The pathological data of 30 cases of PCA were collected; the color Doppler ultrasound, Down's screening, fetal survival, and pathological characteristics were observed; and the literature was reviewed. RESULTS: Of the 30 patients, the ages ranged from 20 to 38 years, with an average of 29.6 years. Pregnancy comorbidity occurred in 14 patients; intrauterine fetal death occurred in 4; the gross appearance of the tumor: a reddish-brown nodule, slightly round, 0.5-8 cm in diameter, can be seen on the cut surface of the placenta Pregnancy comorbidity occurred in 14 patients and intrauterine fetal death in 4. On sectioning the placenta, tumors grossly appeared as reddish-brown nodules, slightly round and ranging in diameter from 0.5 to 8 cm. Microscopically, the tumor has small, densely packed capillaries with fibrous connective tissue in the stroma. There were 10 cases with high risk of Down's syndrome screening, and the immunophenotype CD34 (+) and Ki-67 proliferation index were less than 10%. CONCLUSIONS: PCA is rare and may be misdiagnosed as malignant tumor, which may be related to pregnancy comorbidity and high risk of Down's screening, so improving the understanding of PCA can provide the basis for clinical diagnosis and intervention. PCA is a rare tumor which may be misdiagnosed as a malignancy. It may be related to pregnancy comorbidity and high risk of Down's screening. Improving the understanding of PCA could provide the basis for clinical diagnosis and intervention.

Defect Engineering for Enhanced Electrocatalytic Oxygen Reaction on Transition Metal Oxides: The Role of Metal Defects.

Metal defect engineering is a highly effective strategy for addressing the prevalent high overpotential issues associated with transition metal oxides functioning as dual-function commercial oxygen reduction reaction/oxygen evolution reaction catalysts for increasing their activity and stability. However, the high formation energy of metal defects poses a challenge to the development of strategies to precisely control the selectivity during metal defect formation. Here, density functional theory calculations are used to demonstrate that altering the pathway of metal defect formation releases metal atoms as metal chlorides, which effectively reduces the formation energy of defects. The metal defects on the monometallic metal oxide surface (Mn, Fe, Co, and Ni) are selectively produced using chlorine plasma. The characterization and density functional theory calculations reveal that catalytic activity is enhanced owing to electronic delocalization induced by metal defects, which reduces the theoretical overpotential. Notably, ab initio molecular dynamics calculations, ex situ XPS, and in situ ATR-SEIRAS suggest that metal defects effectively improve the adsorption of reactive species on active sites and enhance the efficiency of product desorption, thereby boosting catalytic performance.

Snowball: a novel gene family required for developmental patterning of fruiting bodies of mushroom-forming fungi (Agaricomycetes).

The morphogenesis of sexual fruiting bodies of fungi is a complex process determined by a genetically encoded program. Fruiting bodies reached the highest complexity levels in the Agaricomycetes; yet, the underlying genetics is currently poorly known. In this work, we functionally characterized a highly conserved gene termed snb1, whose expression level increases rapidly during fruiting body initiation. According to phylogenetic analyses, orthologs of snb1 are present in almost all agaricomycetes and may represent a novel conserved gene family that plays a substantial role in fruiting body development. We disrupted snb1 using CRISPR/Cas9 in the agaricomycete model organism Coprinopsis cinerea. snb1 deletion mutants formed unique, snowball-shaped, rudimentary fruiting bodies that could not differentiate caps, stipes, and lamellae. We took advantage of this phenotype to study fruiting body differentiation using RNA-Seq analyses. This revealed differentially regulated genes and gene families that, based on wild-type RNA-Seq data, were upregulated early during development and showed tissue-specific expression, suggesting a potential role in differentiation. Taken together, the novel gene family of snb1 and the differentially expressed genes in the snb1 mutants provide valuable insights into the complex mechanisms underlying developmental patterning in the Agaricomycetes. IMPORTANCE: Fruiting bodies of mushroom-forming fungi (Agaricomycetes) are complex multicellular structures, with a spatially and temporally integrated developmental program that is, however, currently poorly known. In this study, we present a novel, conserved gene family, Snowball (snb), termed after the unique, differentiation-less fruiting body morphology of snb1 knockout strains in the model mushroom Coprinopsis cinerea. snb is a gene of unknown function that is highly conserved among agaricomycetes and encodes a protein of unknown function. A comparative transcriptomic analysis of the early developmental stages of differentiated wild-type and non-differentiated mutant fruiting bodies revealed conserved differentially expressed genes which may be related to tissue differentiation and developmental patterning fruiting body development.

Quantitative detection and prognostic value of antibodies against M-type phospholipase A2 receptor and its cysteine-rich ricin domain and C-type lectin domains 1 and 6-7-8 in patients with idiopathic membranous nephropathy.

BACKGROUND: M-type phospholipase A2 receptor (PLA2R) is the major autoantigen in adult idiopathic membranous nephropathy (IMN). Although reactive epitopes in the PLA2R domains have been identified, the clinical value of these domains recognized by anti-PLA2R antibodies remains controversial. Accordingly, this study aimed to quantitatively detect changes in the concentrations of different antibodies against epitopes of PLA2R in patients with IMN before and after treatment to evaluate the clinical value of epitope spreading. METHODS: Highly sensitive time-resolved fluorescence immunoassay was used to quantitatively analyze the concentrations of specific IgG and IgG4 antibodies against PLA2R and its epitopes (CysR, CTLD1, CTLD6-7-8) in a cohort of 25 patients with PLA2R-associated membranous nephropathy (13 and 12 in the remission and non-remission groups, respectively) before and after treatment, and the results were analyzed in conjunction with clinical biochemical indicators. RESULTS: The concentration of specific IgG (IgG4) antibodies against PLA2R and its epitopes (CysR, CTLD1 and CTLD6-7-8) in non-remission group was higher than that in remission group. The multipliers of elevation of IgG (IgG4) antibody were 5.6(6.2) fold, 3.0(24.3) fold, 1.6(9.0) fold, and 4.2(2.6) fold in the non-remission/remission group, respectively. However, the difference in antibody concentrations between the two groups at the end of follow-up was 5.6 (85.2), 1.7 (13.1), 1.0 (5.1), and 1.5 (22.3) times higher, respectively. When detecting concentrations of specific IgG antibodies against PLA2R and its different epitopes, the remission rate was 66.67% for only one epitope at M0 and 36.36% for three epitopes at M0. When detecting concentrations of specific IgG4 antibodies against PLA2R and its different epitopes, the remission rate was 100.00% for only one epitope at M0 and 50.00% for three epitopes at M0. A trivariate logistic regression model for the combined detection of eGFR, anti-CTLD678 IgG4, and urinary protein had an AUC of 100.00%. CONCLUSION: Low concentrations of anti-CysR-IgG4, anti-CTLD1-IgG4, and anti-CTLD6-7-8-IgG4 at initial diagnosis predict rapid remission after treatment. The use of specific IgG4 against PLA2R and its different epitopes combined with eGFR and urinary protein provides a better assessment of the prognostic outcome of IMN.

RNS2 is required for the biogenesis of a wounding responsive 16 nts tsRNA in Arabidopsis thaliana.

tRNA-derived small RNAs (tsRNAs), a new category of regulatory small non-coding RNA existing in almost all branches of life, have recently attracted broad attention. Increasing evidence has shown that tsRNAs are not random degradation debris of tRNAs, but products cleaved by specific endoribonucleases, with versatile functions in response to various developmental and environmental cues. However, it is still unclear about the diversity, biogenesis and function of tsRNAs in plants. In this study, we comprehensively profiled 10-60 nts small RNAs in Arabidopsis thaliana leaf with or without wounding stress and identified four 16 nts tiny tRFs (tRNA-derived fragments) sharply increased after wounding, namely tRF5'Ala. Notably, genetic, biochemical and bioinformatic data indicated that RNS2, a member of class II RNase T2 enzymes, was the main endoribonuclease responsible for the biogenesis of tRF5'Ala. Moreover, tRF5'Ala was highly abundant and conserved in Arabidopsis and rice pollen. However, tRF5'Ala did not associate with AGO 1 in vivo or display any inhibitory effect on the translation of a luciferase mRNA in vitro. Altogether, our study highlights the discovery of a novel class of tiny tsRNAs drastically increased under wounding stress as well as their generation by RNS2, which provides a new insight into tsRNAs research in plants.

Diluting the Resistance of Built-in Electric Fields in Oxygen Vacancy-enriched Ru/NiMoO4-x for Enhanced Hydrogen Spillover in Alkaline Seawater Splitting.

Recently, hydrogen spillover based binary (HSBB) catalysts have received widespread attention due to the sufficiently utilized reaction sites. However, the specific regulation mechanism of spillover intensity is still unclear. Herein, we have fabricated oxygen vacancies enriched Ru/NiMoO4-x to investigate the internal relationship between electron supply and mechanism of hydrogen spillover enhancement. The DFT calculations cooperate with in situ Raman spectrum to uncover that the H* spillover from NiMoO4-x to Ru. Meanwhile, oxygen vacancies weakened the electron supply from Ru to NiMoO4-x , which contributes to dilute the resistance of built-in electric field (BEF) for hydrogen spillover. In addition, the higher ion concentration in electrolyte will promote the H* adsorption step obviously, which is demonstrated by in situ EIS tests. As a result, the Ru/NiMoO4-x exhibits a low overpotential of 206 mV at 3.0 A cm-2 , a small Tafel slope of 28.8 mV dec-1 , and an excellent durability of 550 h at the current density of 0.5 A cm-2 for HER in 1.0 M KOH seawater.

A Triptycene-Based Layered/Flower-Like 2D Conductive Metal-Organic Framework with 3D Extension as an Electrode for Efficient Li Storage.

2D metal-organic frameworks (2D MOFs) with π conjugation have attracted widespread attention in the field of lithium storage due to their unique electron transfer units and structural characteristics. However, the periodic 2D planar extension structure hides some active sites, which is not conducive to the utilization of its structural advantages. In this work, a series of triptycene-based 2D conductive MOFs (M-DBH, M = Ni, Mn, and Co) with 3D extension structures are constructed by coordinating 9,10-dihydro-9,10-[1,2]benzenoanthracene-2,3,6,7,14,15-hexaol with metal ions to explore their potential applications in lithium-ion and lithium-sulfur batteries. This is the first study in which 2D conductive MOFs with the 3D extended molecule are used as electrode materials for lithium storage. The designed material generates rich active sites through staggered stacking layers and shows excellent performance in lithium-ion and lithium-sulfur batteries. The capacity retention rate of Ni-DBH can reach over 70% after 500 cycles at 0.2 C in lithium-ion batteries, while the capacity of S@Mn-DBH exceeds 305 mAh g-1 after 480 cycles at 0.5 C in lithium-sulfur batteries. Compared with the materials with 2D planar extended structures, the M-DBH electrodes with 3D extended structures in this work exhibit better performance in terms of cycle time and lithium storage capacity.

Manipulating Electron Redistribution in Ni2 P for Enhanced Alkaline Seawater Electrolysis.

Developing bifunctional electrocatalyst for seawater splitting remains a persistent challenge. Herein, an approach is proposed through density functional theory (DFT) preanalysis to manipulate electron redistribution in Ni2 P addressed by cation doping and vacancy engineering. The needle-like Fe-doped Ni2 P with P vacancy (Fe-Ni2 Pv) is successfully synthesized on nickel foam, exhibiting a superior bifunctional hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) catalytic activity for seawater electrolysis in alkaline condition. As a result, bifunctional Fe-Ni2 Pv achieves the industrially required current densities of 1.0 and 3.0 A cm-2 at low voltages of 1.68 and 1.73 V, respectively, for seawater splitting at 60 °C in 6.0 m KOH circumstances. The theoretical calculation and the experimental results collectively reveal the reasons for the enhancement of catalyst activity. Specifically, Fe doping and P vacancies can accelerate the reconstruction of OER active species and optimize the hydrogen adsorption free energy (ΔGH* ) for HER. In addition, the active sites of Fe-Ni2 Pv are identified, where P vacancies greatly improve the electrical conductivity and Ni sites are the dominant OER active centers, meanwhile Fe atoms as active centers for the HER. The study provides a deep insight into the exploration for the enhancement of activity of nickel-based phosphide catalysts and the identification of their real active centers.

A Bibliometric Analysis of the Trends and Evolution on Inhalation Injury Research.

Inhalation injury is a common complication in burn patients and is also a factor that can affect the multiple prognoses of burn patients. Attention to inhalation injury began early globally, but few articles have systematically analyzed its development. We employed bibliometric methods to analyze articles on inhalation injury published in 3 medical databases. A total of 3056 relevant articles on inhalation injury were included in our analysis and divided into 3 distinct periods based on Price's law. Notably, a slowdown in publication growth was observed in period III. The majority of these articles were authored by a small group of individuals, with a significant proportion of them being American scholars. In fact, nearly half of the articles were published by American researchers. Applying Bradford's Law, we identified 4 major output sources in the field, namely Burns, Journal of Burn Care & Research, Journal of Trauma, and Critical Care Medicine. Recent research has focused on the clinical risks and outcomes associated with inhalation injury, while basic research in this area has been relatively neglected over the last decade. In conclusion, the growth of publications on inhalation injuries has largely followed standard scientific growth patterns, with a small number of countries and established research groups contributing the majority of articles. However, the recent slowdown in scientific output is a cause for concern, and the lack of emphasis on basic research and clinical trials in this field raises questions about the foundation for widespread clinical management of inhalation injuries.

Mn Doping and P Vacancy Induced Fast Phase Reconstruction of FeP for Enhanced Electrocatalytic Oxygen Evolution Reaction in Alkaline Seawater.

Due to the shortage of pure water resources, seawater electrolysis is a promising strategy to produce green hydrogen energy. To avoid chlorine oxidation reactions (ClOR) and the production of more corrosive hypochlorite, enhancing OER electrocatalyst activity is the key to solving the above problem. Considering that transition metal phosphides (TMPs) are promising OER eletrocatalysts for seawater splitting, a method to regulate the electronic structure of FeP by introducing Mn heteroatoms and phosphorus vacancy on it (Mn-FePV ) is developed. As an OER electrocatalyst in seawater solution, the synthesized Mn-FePV achieves extremely low overpotentials (η500  = 376, η1000  = 395 mV). In addition, the Pt/C||Mn-FePV couple only requires the voltage of 1.81 V to drive the current density of 1000 mA cm-2 for overall seawater splitting. The density functional theory (DFT) calculation shows that Mn-FePV (0.21 e- ) has more charge transfer number compared with FeP (0.17 e- ). In-situ Raman analysis shows that phosphorus vacancy and Mn doping can synergistically regulate the electronic structure of FeP to induce rapid phase reconstruction, further improving the OER performance of Mn-FePV . The new phase species of FeOOH is confirmed to can enhance the adsorption kinetics of OER intermediates.

[Saikosaponin D regulates apoptosis and autophagy of pancreatic cancer Panc-1 cells via Akt/mTOR pathway].

This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 µmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 µmol·L~(-1)), low-concentration(10 µmol·L~(-1)) saikosaponin D, and high-concentration(16 µmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3Ⅱ/LC3Ⅰ and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.

KHDRBS3 accelerates glycolysis and promotes malignancy of hepatocellular carcinoma via upregulating 14-3-3ζ.

BACKGROUND: Primary hepatocellular carcinoma (HCC) is a malignancy with high morbidity and mortality. KH domain-containing, RNA-binding signal transduction-associated protein 3 (KHDRBS3) is an RNA-binding protein that is aberrantly expressed in multiple tumors; however, its expression and biological function in HCC have not been reported. METHODS: KHDRBS3 knockdown and overexpression were performed using the lentiviral vector system to investigate the effects of KHDRBS3 on cell proliferation, apoptosis, chemoresistance, and glycolysis. Murine xenograft tumor models were constructed to study the role of KHDRBS3 on tumor growth in vivo. Furthermore, RNA-Pull Down and RNA immunoprecipitation were utilized to explore the interaction between KHDRBS3 and 14-3-3ζ, a phosphopeptide-binding molecule encoded by YWHAZ. RESULTS: KHDRBS3 was highly expressed in human HCC tissues and predicted the poor prognosis of patients with HCC. Knockdown of KHDRBS3 exhibited a carcinostatic effect in HCC and impeded proliferation and tumor growth, reduced glycolysis, enhanced cell sensitivity to doxorubicin, and induced apoptosis. On the contrary, forced expression of KHDRBS3 expedited the malignant biological behaviors of HCC cells. The expression of KHDRBS3 was positively correlated with the expression of 14-3-3ζ. RNA immunoprecipitation and RNA pull-down assays demonstrated that KHDRBS3 bound to YWHAZ. We further confirmed that 14-3-3ζ silencing significantly reversed the promotion of proliferation and glycolysis and the inhibition of apoptosis caused by KHDRBS3 overexpression. CONCLUSIONS: Our findings suggest that KHDRBS3 promotes glycolysis and malignant progression of HCC through upregulating 14-3-3ζ expression, providing a possible target for HCC therapy.

Improved MobileNetV2 crop disease identification model for intelligent agriculture.

Using intelligent agriculture is an important way for the industry to achieve high-quality development. To improve the accuracy of the identification of crop diseases under conditions of limited computing resources, such as in mobile and edge computing, we propose an improved lightweight MobileNetV2 crop disease identification model. In this study, MobileNetV2 is used as the backbone network for the application of an improved Bottleneck structure. First, the number of operation channels is reduced using point-by-point convolution, the number of parameters of the model is reduced, and the re-parameterized multilayer perceptron (RepMLP) module is introduced; the latter can capture long-distance dependencies between features and obtain local a priori information to enhance the global perception of the model. Second, the efficient channel-attention mechanism is added to adjust the image-feature channel weights so as to improve the recognition accuracy of the model, and the Hardswish activation function is introduced instead of the ReLU6 activation function to further improve performance. The final experimental results show that the improved MobilNetV2 model achieves 99.53% accuracy in the PlantVillage crop disease dataset, which is 0.3% higher than the original model, and the number of covariates is only 0.9M, which is 59% less than the original model. Also, the inference speed is improved by 8.5% over the original model. The crop disease identification method proposed in this article provides a reference for deployment and application on edge and mobile devices.

Chimeric kinase ALK induces expression of NAMPT and selectively depends on this metabolic enzyme to sustain its own oncogenic function.

As we show in this study, NAMPT, the key rate-limiting enzyme in the salvage pathway, one of the three known pathways involved in NAD synthesis, is selectively over-expressed in anaplastic T-cell lymphoma carrying oncogenic kinase NPM1::ALK (ALK + ALCL). NPM1::ALK induces expression of the NAMPT-encoding gene with STAT3 acting as transcriptional activator of the gene. Inhibition of NAMPT affects ALK + ALCL cells expression of numerous genes, many from the cell-signaling, metabolic, and apoptotic pathways. NAMPT inhibition also functionally impairs the key metabolic and signaling pathways, strikingly including enzymatic activity and, hence, oncogenic function of NPM1::ALK itself. Consequently, NAMPT inhibition induces cell death in vitro and suppresses ALK + ALCL tumor growth in vivo. These results indicate that NAMPT is a novel therapeutic target in ALK + ALCL and, possibly, other similar malignancies. Targeting metabolic pathways selectively activated by oncogenic kinases to which malignant cells become "addicted" may become a novel therapeutic approach to cancer, alternative or, more likely, complementary to direct inhibition of the kinase enzymatic domain. This potential therapy to simultaneously inhibit and metabolically "starve" oncogenic kinases may not only lead to higher response rates but also delay, or even prevent, development of drug resistance, frequently seen when kinase inhibitors are used as single agents.