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[This corrects the article DOI: 10.1371/journal.pone.0288788.].

Abstract Background The oil-soluble contrast medium used in hysterosalpingography has been shown to have a fertility-enhancing effect, but the underlying mechanism is unclear, especially regarding the role of window of implantation (WOI). This study aimed to assess the endometrial immunological impact of the WOI before and after bathing with the oil-soluble contrast medium in women with recurrent implantation failure (RIF). Methods This descriptive study involved two medical centers between December 18, 2019, and December 30, 2020. We included infertile women who underwent three or more transfer cycles, cumulative transplantation of at least four high-quality cleavage-stage embryos or three high-quality blastocysts without clinical pregnancy, and high-quality frozen embryos that were still available for implantation. Patients received 5 ml of ethiodized poppyseed oil bathing, endometrial biopsy around bathing, and frozen-thawed embryo transfer (FET) within four menstrual cycles after bathing. Patients were excluded if failure to complete anyone. Data on the baseline characteristics and clinical data of the FET cycles were collected, and endometrial biopsy specimens were collected in the luteal phase before and after bathing and subjected to immunohistochemistry. The number of CD56 and CD138 positive cells and H-score of expression of ανβ-3 and HOXA10 in endometrium were collected. Results Thirty-four patients were initially enrolled in the study; ultimately, twelve patients with a median age of 32.5 years (range 27–40 years) completed the research. The median number of embryo transfer cycles was three (range 3–8). A total of 4 of 12 women (33.33%) were diagnosed with chronic endometritis before oil-soluble contrast bathing. After bathing, the median numbers of CD138-positive cells in endometrium decreased from 0.75 (range 0–13.5) to 0.65 (range 0–6), P = 0.035; additionally, the H-score of expression of ανβ-3 in endometrium increased from 148.50 ± 31.63 to 175.58 ± 31.83, P

【Objective】In mammals, Toll-like receptors and antimicrobial peptide genes are important components of the innate immune system, which play a crucial role in fighting against pathogen attacks. The study was conducted to explore the expression differences of Toll-like receptor and antimicrobial peptide genes between different immune organs or tissues in Tibetan pigs and Duroc-Landrace-Yorkshire pigs, with an aim to reveal the potential contribution of these genes to disease resistance and immune response and provide theoretical support for the screening of molecular markers for disease resistance.【Method】The mRNA abundance of Toll-like receptors genes (TLR1-TLR9) and two types of antimicrobial peptide genes (PBD-1 and PR-39) in lungs, mesenteric lymph nodes, inguinal lymph nodes, submandibular lymph nodes and spleens of 6-month-old Tibetan and Duroc-Landrace-Yorkshire pigs were detected by qPCR.【Result】The mRNA expression of Tolllike receptors and antimicrobial peptide genes in most of the immune organs or tissues of Tibetan pigs was significantly higher than that of Duroc-Landrace-Yorkshire pigs. Among them, the mRNA expression of TLR1 and TLR2 in lungs was increased by about 50%, and PR-39 was increased by 2.6 times; the expression of TLR4 in mesenteric lymph nodes was increased by 40%, and the expression of TLR1 and PR-39 was increased by 88% and 3 times, respectively. In the inguinal lymph nodes, the expression of TLR1 and TLR2 was increased by about 2 times, and the expression of TLR9 and PR-39 was increased by 70%, especially, the expression of PR-39 increasing by 7 times; The expression of TLR1, TLR2, TLR4 and TLR7 in submandibular lymph nodes was increased by more than 2 times, and the expression of PR-39 was increased by nearly 7 times, which was similar to that in inguinal lymph nodes; the expression of TLR1 in the spleen rose by 3.5 times, which was similar to that in submandibular lymph nodes. The expression of TLR4 and TLR9 increased by about 50%, and the expression of PR-39 increased by 2.5 times.【Conclusion】Tibetan pigs show higher expression levels of Toll-like receptors and antimicrobial peptide genes in multiple immune organs or tissues compared to Duroc-Landrace-Yorkshire pigs. It is implied that Tibetan pigs may possess stronger innate immunity and be able to generate more effective local or systemic immune responses against pathogenic microbial infections. The results of this study provide important theoretical support for the identification of disease resistance molecular markers and are expected to provide a scientific basis for further improvement of disease resistance in Tibetan pigs and other pig breeds.

Transplantations represent the principal therapeutic interventions for terminal organ failure, a procedure that has salvaged myriad lives annually. Ischemia/reperfusion injury (IRI) is frequently correlated with an unfavourable prognosis and is relevant for early graft dysfunction and graft survival. IRI constitutes a complex pathological state influenced by a series of factors such as oxidative stress, metabolic stress, leukocytic infiltration, programmed cell death pathways, and inflammatory immune responses. Reducing ischemia/reperfusion injury is one of the main directions of transplantation research. Toll-like receptors (TLRs) are important pattern-recognition receptors expressed on various organs that orchestrate the immune responses upon recognising PAMPs and DAMPs. Targeting the TLR4 signalling has recently been suggested as a promising approach for alleviating IRI by affecting inflammation, oxidative stress and programmed cell death (PCD). In this minireview, we summarise the role of TLR4 signalling in regulating inflammation, oxidative stress and PCD in organ transplantation and discuss their interactions during IRI. A detailed understanding of the multiple functions of TLR4 in IRI provides novel insights into developing therapies to improve organ transplantation outcomes.

Adipose tissue, an indispensable organ, fulfils the pivotal role of energy storage and metabolism and is instrumental in maintaining the dynamic equilibrium of energy and health of the organism. Adipocyte hypertrophy and adipocyte hyperplasia (adipogenesis) are the two primary mechanisms of fat deposition. Mature adipocytes are obtained by differentiating mesenchymal stem cells into preadipocytes and redifferentiation. However, the mechanisms orchestrating adipogenesis remain unclear. Autophagy, an alternative cell death pathway that sustains intracellular energy homeostasis through the degradation of cellular components, is implicated in regulating adipogenesis. Furthermore, adipose tissue functions as an endocrine organ, producing various cytokines, and certain inflammatory factors, in turn, modulate autophagy and adipogenesis. Additionally, autophagy influences intracellular redox homeostasis by regulating reactive oxygen species, which play pivotal roles in adipogenesis. There is a growing interest in exploring the involvement of autophagy, inflammation, and oxidative stress in adipogenesis. The present manuscript reviews the impact of autophagy, oxidative stress, and inflammation on the regulation of adipogenesis and, for the first time, discusses their interactions during adipogenesis. An integrated analysis of the role of autophagy, inflammation and oxidative stress will contribute to elucidating the mechanisms of adipogenesis and expediting the exploration of molecular targets for treating obesity-related metabolic disorders.

Objective: In order to explore the mechanisms behind the anti-inflammatory potentials of black tea from Camellia ptilophylla Chang (C. ptilophylla) (BTCP). Method: The bioactive components of the methanol extracts of BTCP were firstly detected via ultra-high performance liquid chromatography-quadrupole orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). Additionally, the bioactive components, targets, and signal pathways involved in the anti-inflammatory effects of BTCP were predicted by network pharmacology (NP). Then, the interactions between the bioactive components and the targets were evaluated using molecular docking (MD). Finally, Inflammatory cell model was used to verify the inhibitory effects of the bioactive components on nitric oxide in vitro, a pro-inflammatory cytokine. Result: A total of 213 active components were identified from BTCP, and the core anti-inflammatory polyphenols such as anthocyanin, naringin, luteolin and quercetin were screened. In addition, 493 potential anti-inflammatory targets were collected, and tumor necrosis factor (TNF), interleukin (IL-6) were predicted. IL-6 and other nine key targets and phosphatidylinositol 3-kinase/protein kinase B, PI3K-Akt, mitogen-activated protein kinase (MAPK) and other signaling pathways. Preliminary results showed that eleven anti-inflammatory active components, especially nine polyphenols such as luteolin, could stably bind to the main target, and luteolin and quercetin could significantly inhibit the production of nitric oxide (NO) in mouse macrophage RAW264.7 induced by lipaccharide. The semi-inhibitory concentrations were 18.91 and 43.76 μmol/L, respectively. Conclusion: Polyphenol compounds such as luteolin in BTCP would exert remarkable anti-inflammatory activity through the regulation on multiple targets including TNF and IL-6 and various pathways such as PI3K-Akt and MAPK. The present study provides a theoretical basis for further elucidation of the anti-inflammatory potentials of C. ptilophylla.

PTD-FNK, a synthetic anti-apoptotic protein, has been shown to potently alleviate cellular injuries. However, the effects of PTD-FNK on oxidative defense in boar testicular Sertoli cells (SCs) against oxidative injury has not been explored. In this study, we show that exposure of SCs to 100 mg/L lipopolysaccharide (LPS) for 12 h leads to decreased survival rate, superoxide dismutase (SOD) activity, and increased malondialdehyde (MDA). Treatment with 0.01 nmol/L PTD-FNK for 4 h significantly enhanced the activity of SOD, catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in SCs. Concurrently, PTD-FNK treatment effectively reduced the production of reactive oxygen species (ROS) and the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) in SCs. Moreover, using His pull-down and LC-MS techniques, we identified PTD-FNK-interacting proteins and confirmed that this protective effect may be mediated by the regulation of the Keap1-Nrf2 signaling pathway by PTD-FNK. Therefore, PTD-FNK alleviates LPS-induced oxidative stress via the Keap1/Nrf2 pathway, providing novel insights for the development of therapeutic agents targeting testicular oxidative damage.

An investigation into the corrosion characteristics and mechanism of directionally solidified (DSed) Mg-3Zn-xCa (x = 0, 0.2, 0.5, 0.8 wt.%) alloys in 0.9 wt.% NaCl solution is presented. The DSed microstructure consists of columnar dendrites and eutectics distributed in the interdendritic region. The primary dendritic arm spacing (PDAS) and the volume fraction (fv) of the secondary phases are under the significant impact of the content of Ca. The corrosion rates evaluated using electrochemical measurements and immersion tests are accelerated monotonously with the increase of Ca content in DSed alloys. The corrosion resistance of the DSed alloys is significantly affected by the corrosion products film (CPF) and the secondary phases. The corrosion products of DSed Mg-3Zn alloy contain Mg(OH)2 and ZnO. The existence of ZnO greatly enhances the corrosion resistance of DSed Mg-3Zn alloy. As for the DSed alloys containing Ca content, a relatively protective CPF without deep pits can form on the surface of DSed Mg-3Zn-0.2Ca specimen during the corrosion. The fv of the secondary phases dominates the corrosion rate of the DSed Mg-Zn-Ca alloys. The corrosion of DSed Mg-3Zn-xCa alloys initiates as a result of micro-galvanic coupling between the cathodes of secondary phases and α-Mg matrix anode. Then, the corrosion gradually extends longitudinally with the breakdown of CPF.

BackgroundThis study investigates the potential impact of high progesterone (P) level on the day following human chorionic gonadotropin (HCG) injection on the clinical pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET).MethodsRetrospective analysis was conducted on 6418 cycles of IVF-ET performed at Liuzhou Maternal and Child Health Hospital between August 2020 to December 2021. Excluding cycles with progesterone levels ≥1.5ng/ml on HCG injection, a total of 781 cycles were identified according to the standard, and they were divided into five groups according to the progesterone level on the day after HCG: Group A: progesterone level < 2.5 ng/ml (n = 128); Group B: 2.5 ng/ml ≤ progesterone level < 3.5 ng/ml (n = 174); Group C: 3.5 ng/ml ≤ progesterone level < 4.5 ng/ml (n = 153); Group D: 4.5 ng/ml ≤ progesterone level < 5.5 ng/ml (n = 132); Group E progesterone level ≥5.5 ng/ml(n=194). Comparative analyses of clinical data, including general clinical data, and clinical pregnancy outcomes such as clinical pregnancy rate, miscarriage rate, and live birth rate were performed among these groups.ResultsThere were significant differences in estradiol levels on HCG injection, but there were no differences in available embryo rate, clinical pregnancy rate, miscarriage rate, and live birth rate. Binary logistic regression analysis showed that there was no significant correlation between P level on the day after HCG injection and the live birth rate.ConclusionUnder the condition of low P level on HCG injection, high progesterone levels on the day after HCG injection does not affect the clinical pregnancy outcomes of IVF-ET.

Recent studies suggested that cancer was a risk factor for coronavirus disease 2019 (COVID-19). Toll-like receptor 7 (TLR7), a severe acute respiratory syndrome 2 (SARS-CoV-2) virus's nucleic acid sensor, was discovered to be aberrantly expressed in many types of cancers. However, its expression pattern across cancers and association with COVID-19 has not been systematically studied. In this study, we proposed a computational framework to comprehensively study the roles of TLR7 in COVID-19 and pan-cancers at genetic, gene expression, protein, epigenetic, and single-cell levels. We found TLR7 mRNA expression was significantly up-regulated in 6 cancer types and down-regulated in 6 cancer types, further validated in the HPA database at the protein level. The genes significantly co-expressed with TLR7 were mainly enriched in the toll-like receptor signaling pathway, endolysosome, and signaling pattern recognition receptor activity. In addition, the abnormal TLR7 expression was associated with Mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB) in various cancers. Mined by the ESTIMATE algorithm, the expression of TLR7 was also closely linked to various immune infiltration patterns in pan-cancer, and TLR7 was mainly enriched in macrophages, as revealed by single-cell RNA sequencing. Finally, TLR7 expressions were very sensitive to a few targeted drugs, such as Alectinib and Imiquimod. In conclusion, TLR7 might be essential in the pathogenesis of COVID-19 and cancers.

Study region: Southwest China (97.4ºE∼112.1ºE, 21.1ºN∼34.3ºN), including Sichuan, Yunnan, Guizhou, Chongqing, and Guangxi provinces. Study focus: Meteorological droughts were likely to become much more frequent and intensified, posing a huge threat to food security, drinking water supply, ecological environment security, and sustainable development of economy and society. However, the spatial and temporal variations of seasonal droughts and its possible driving forces are still not fully understood. In this work, we deeply explored the spatial and temporal variations of spring drought in Southwest China and its possible teleconnection mechanisms during 1961–2020. New hydrological insights for the region: The rising temperature and reduced precipitation led to a significant worsen trend of spring drought in the eastern parts of Southwest China (ESWC) during 1961–2020. Significant abrupt changes of spring drought occurred in 2003, and spring drought became much more frequent and intensified especially after 2003 in ESWC. Spring drought evolutions were dominated by NAO, and were also affected by the coupling of TNA and AO in ESWC during 1961–2020. However, the significant worsen trend of spring drought during 2003–2020 in ESWC could be largely explained by the coupling influences of NAO, TNA, and PDO. These results can provide valuable information for agricultural production, water resource management, and especially the early warning and prediction of spring drought in Southwest China.

The host defence responses play vital roles in viral infection and are regulated by complex interactive networks. The host immune system recognizes viral pathogens through the interaction of pattern-recognition receptors (PRRs) with pathogen-associated molecular patterns (PAMPs). As a PRR mainly in the cytoplasm, cyclic GMP-AMP synthase (cGAS) senses and binds virus DNA and subsequently activates stimulator of interferon genes (STING) to trigger a series of intracellular signalling cascades to defend against invading pathogenic microorganisms. Integrated omic and functional analyses identify the cGAS-STING pathway regulating various host cellular responses and controlling viral infections. Aside from its most common function in regulating inflammation and type I interferon, a growing body of evidence suggests that the cGAS-STING signalling axis is closely associated with a series of cellular responses, such as oxidative stress, autophagy, and endoplasmic reticulum stress, which have major impacts on physiological homeostasis. Interestingly, these host cellular responses play dual roles in the regulation of the cGAS-STING signalling axis and the clearance of viruses. Here, we outline recent insights into cGAS-STING in regulating type I interferon, inflammation, oxidative stress, autophagy and endoplasmic reticulum stress and discuss their interactions with viral infections. A detailed understanding of the cGAS-STING-mediated potential antiviral effects contributes to revealing the pathogenesis of certain viruses and sheds light on effective solutions for antiviral therapy.

Magnesium alloys with homogeneous degradation and controlled degradation rate are desirable for biodegradable materials. In the present work, Mg-3 wt.%Zn-0.2 wt.%Ca alloys with different columnar structures were fabricated and the degradation in 0.9 wt.% NaCl were investigated. With the increase of the growth rate for the directional solidification, the microstructure of the directionally solidified (DSed) alloy evolved from cellular to dendritic coupled with the change of the spacing of the primary trunks (λ1) and the volume fraction (fv) of Ca2Mg6Zn3 phase. The results of the corrosion test suggested that the alloy with cellular structure experienced homogeneous corrosion and exhibited the lowest corrosion rate. The good corrosion resistance of the alloy with cellular structure was attributed to the protective corrosion products film (CPF), which was closely related to the fv of Ca2Mg6Zn3 phase and λ1. To evaluate the corrosion rates (CR) of the DSed Mg-Zn-Ca alloys with different microstructures, a parameter α was proposed in this work, which was calculated by λ1 and the fv of Ca2Mg6Zn3 phase. The fitting result showed that there was a linear relationship between CR and α, which was CR = 4.1899 + 0.00432α. This means that the CR of the DSed Mg-Zn-Ca alloy can be evaluated if the microstructure had been characterized.

Abstract Background Several risk factors of immune checkpoint inhibitors (ICIs)-associated acute kidney injury (AKI) have been reported sporadically. To identify the risk factors of ICIs-associated AKI in a large-scale population, therefore we conducted a systematic review and a real-world retrospective study. Methods We search literature concerning risk factors of ICIs-associated AKI in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to January 2022. Meta-analysis was performed by using odds ratios (ORs) with 95%CIs. In a separate retrospective pharmacovigilance study by extracting data from US FDA Adverse Event Reporting System (FAERS) database, disproportionality was analyzed using the reporting odds ratio (ROR). Results A total of 9 studies (5927 patients) were included in the meta-analysis. The following factors were associated with increased risk of ICIs-associated AKI, including proton pump inhibitors(PPIs) (OR = 2.07, 95%CI 1.78–2.42), angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) (OR = 1.56, 95%CI 1.24–1.95), nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 1.29, 95%CI 1.01–1.65), diuretics (OR = 2.00, 95%CI 1.38–2.89), diabetes mellitus (OR = 1.28, 95%CI 1.04–1.57), genitourinary cancer (OR = 1.46, 95%CI 1.15–1.85), combination therapy of ICIs (OR = 1.93, 95%CI 1.25–2.97) and extrarenal immune-related adverse events(irAEs) (OR = 2.51, 95%CI 1.96–3.20). Furthermore, analysis from FAERS database verified that concurrent exposures of PPIs (ROR = 2.10, 95%CI 1.91–2.31), ACEIs/ARBs (ROR = 3.25, 95%CI 2.95–3.57), NSAIDs (ROR = 3.06, 95%CI 2.81–3.32) or diuretics (ROR = 2.82, 95%CI 2.50–3.19) were observed significant signals associated with AKI in ICIs-treated patients. Conclusions Concurrent exposures of PPIs, ACEIs/ARBs, NSAIDs or diuretics, diabetes mellitus, genitourinary cancer, combination therapy, and extrarenal irAEs seem to increase the risk of AKI in ICIs-treated patients.

The efficient management of commercial orchards strongly requires accurate information on plant growing status for the implementation of necessary farming activities such as irrigation, fertilization, and pest control. Crown planar area and plant number are two very important parameters directly relating to fruit growth conditions and the final productivity of an orchard. In this study, in order to propose a novel and effective method to extract the crown planar area and number of mature and young papayas based on visible light images obtained from a DJ Phantom 4 RTK, we compared different vegetation indices (NGRDI, RGBVI, and VDVI), filter types (high- and low-pass filters), and filter convolution kernel sizes (3–51 pixels). Then, Otsu’s method was used to segment the crown planar area of the papayas, and the mean–standard deviation threshold (MSDT) method was used to identify the number of plants. Finally, the extraction accuracy of the crown planar area and number of mature and young papayas was validated. The results show that VDVI had the highest capability to separate the papayas from other ground objects. The best filter convolution kernel size was 23 pixels for the low-pass filter extraction of crown planar areas in mature and young plants. As to the plant number identification, segmentation could be set to the threshold with the highest F-score, i.e., the deviation coefficient n = 0 for single young papaya plants, n = 1 for single mature ones, and n = 1.4 for crown-connecting mature ones. Verification indicated that the average accuracy of crown planar area extraction was 93.71% for both young and mature papaya orchards and 95.54% for extracting the number of papaya plants. This set of methods can provide a reference for information extraction regarding papaya and other fruit trees with a similar crown morphology.

Pigs are highly valued in both agriculture and medicine. We can quickly improve the economic properties of pigs and develop human disease models via gene modification technologies. CRISPR/Cas9 gene editing technology, with the advantages of simple operation, high efficiency and low cost, is widely applied in modifying pig genes. However, CRISPR/Cas9, due to its proneness to cause problems including structural instability of the genomes, large-scale chromosomal rearrangement and gene off-target, could pose potential risks to biological safety. In recent years, the base editing technology based on CRISPR/Cas9 can achieve the directional conversion of a single base without causing DNA double-strand breaks and insertion or loss (Indels), which is more precise and safer for gene editing. With the continuous development and improvement of base editing tools, it is not only able to produce base C → T (A → G) mutations, but also to produce simultaneous mutations of two bases (C and A) and base C → G, increasing the scope of application. improved base editing tools can reduce or even eliminate collateral mutations while maintaining editing efficiency, no C → T (A → G) mutations and Indels, making base editing technology has more important potential applications in pig genetic modification. In order to provide references for the application of base editing in pigs, the study reviews the systemic mechanism of different base editing technologies, the application of base editing technologies in the construction of genetically modified pig models and the genetic improvement of pigs as well as the editing efficiency and off-target situation of base editing systems in pig fibroblasts.

The precise estimation of sugarcane yield at the field scale is urgently required for harvest planning and policy-oriented management. Sugarcane yield estimation from satellite remote sensing is available, but satellite image acquisition is affected by adverse weather conditions, which limits the applicability at the field scale. Secondly, existing approaches from remote sensing data using vegetation parameters such as NDVI (Normalized Difference Vegetation Index) and LAI (Leaf Area Index) have several limitations. In the case of sugarcane, crop yield is actually the weight of crop stalks in a unit of acreage. However, NDVI’s over-saturation during the vigorous growth period of crops results in significant limitations for sugarcane yield estimation using NDVI. A new sugarcane yield estimation is explored in this paper, which employs allometric variables indicating stalk magnitude (especially stalk height and density) rather than vegetation parameters indicating the leaf quantity of the crop. In this paper, UAV images with RGB bands were processed to create mosaic images of sugarcane fields and estimate allometric variables. Allometric equations were established using field sampling data to estimate sugarcane stalk height, diameter, and weight. Additionally, a stalk density estimation model at the pixel scale of the plot was created using visible light vegetation indices from the UAV images and ground survey data. The optimal stalk density estimation model was applied to estimate the number of plants at the pixel scale of the plot in this study. Then, the retrieved height, diameter, and density of sugarcane in the fields were combined with stalk weight data to create a model for estimating the sugarcane yield per plot. A separate dataset was used to validate the accuracy of the yield estimation. It was found that the approach presented in this study provided very accurate estimates of sugarcane yield. The average yield in the field was 93.83 Mg ha−1, slightly higher than the sampling yield. The root mean square error of the estimation was 6.63 Mg ha−1, which was 5.18% higher than the actual sampling yield. This study offers an alternative approach for precise sugarcane yield estimation at the field scale.

Abstract Background The association between homocysteine (Hcy) and IgA nephropathy (IgAN) is not well understood. We aimed to investigate the relationship between Hcy and clinicopathologic features in IgAN patients. Methods A total of 337 IgAN patients and 150 sex- and age- matched healthy controls were enrolled in this single-center retrospective study. According to Hcy ≤ 10 μmol/L or > 10 μmol/L, patients were divided into low and high Hcy groups. Multivariate logistic regression was performed to explore the risk factors for elevated Hcy. Results Serum Hcy was higher in IgAN patients than in healthy controls [11.6 (9.1,15.3) vs. 8.8 (7.5,10.6) μmol/L, P

BackgroundLow fertility and adverse pregnancy outcomes are commonly observed in women with chronic kidney disease (CKD). However, a causal relationship between low fertility and adverse pregnancy outcomes with CKD remains unclear. Besides, whether mild kidney dysfunction can affect fertility and pregnancy still needs exploration. Hence, this study aimed to investigate the causal effect of kidney damage on fertility and pregnancy using Mendelian randomization (MR).MethodsWe first used two-sample MR to examine the effects of kidney damage on fertility and pregnancy. Next, we introduced the Bayesian model averaging MR analysis to detect major causal relationships and render the results robust. The genetic instruments and outcome data were derived from various large genome-wide association studies.ResultsAdverse pregnancy outcomes: Our analyses supported a suggestive causal effect of CKD and estimated glomerular filtration rate (eGFR) rapid on stillbirth, with CKD having an odds ratio (OR) of 1.020 [95% confidence interval (CI) 1.002 to 1.038] and eGFR rapid having an OR of 1.026 (95% CI 1.004-1.048). We also discovered a suggestive causal effect of eGFR on spontaneous abortion, with an OR of 2.63 (95% CI 1.269 to 5.450). Moreover, increased urinary albumin-to-creatinine ratio (UACR) was regarded as a potential risk factor for pre-eclampsia (OR = 1.936; 95% CI 1.065 to 3.517) and gestational hypertension (OR = 1.700; 95% CI 1.002 to 2.886). Fertility assessment: The results indicated that eGFR and UACR had a suggestive causal relationship with the anti-Müllerian hormone level (eGFR beta: 1.004; UACR beta: 0.405).ConclusionsOur study used MR to demonstrate a suggestive causal relationship between kidney damage and fertility and pregnancy. We reported that mild kidney dysfunction might be a risk factor for reduced fertility and adverse pregnancy outcomes. Dynamic renal detection may help preserve fertility and reduce the risk of pregnancy loss.

Organ transplantation is the main treatment for end-stage organ failure, which has rescued tens of thousands of lives. Immune rejection is the main factor affecting the survival of transplanted organs. How to suppress immune rejection is an important goal of transplantation research. A graft first triggers innate immune responses, leading to graft inflammation, tissue injury and cell death, followed by adaptive immune activation. At present, the importance of innate immunity in graft rejection is poorly understood. Autophagy, an evolutionarily conserved intracellular degradation system, is proven to be involved in regulating innate immune response following graft transplants. Moreover, there is evidence indicating that autophagy can regulate graft dysfunction. Although the specific mechanism by which autophagy affects graft rejection remains unclear, autophagy is involved in innate immune signal transduction, inflammatory response, and various forms of cell death after organ transplantation. This review summarizes how autophagy regulates these processes and proposes potential targets for alleviating immune rejection.

The low microalloying content and high yield strength of 365 MPa have been achieved simultaneously in extruded Mg–Ce–Al alloy which is mainly ascribed to the unexpected grain refinement (mean size of ∼420 nm). It is found that adding tiny Al (0.05 wt.%) into Mg–0.2 wt.% Ce alloy can promote the formation of Ce–Al-enriched segregation along dislocations and grain boundaries which can effectively counterbalance the thermally activated dislocation recovery and thus guarantee grain refinement. The ultra-fined grains are mainly related to both linear and planar cosegregation of solutes, rather than the traditional planar segregations and/or nanoprecipitations at grain boundaries.

This work reported the effect of extrusion speeds on the microstructures and mechanical properties of Mg-Ca binary alloy. The results showed that yield strength of the as-extruded Mg-1.2 wt.% Ca alloys decrease from ∼ 360 MPa to ∼ 258 MPa as the ram speed increases from 0.4 mm/s to 2.4 mm/s, and the elongation increases from ∼ 3.9% to ∼ 12.2%. The microstructure changes from bimodal grain feature to the complete dynamical recrystallization (DRX) with increase of the extrusion speed. The ultrafine DRXed grains in size of ∼0.85 µm, the numerous nano-Mg2Ca particles dispersing along the grain boundaries and interiors, as well as the high density of residual dislocations, should account for the high strength. It is believed that the high degree of dynamic recrystallization and the resulting texture randomization play the critical roles in the ductility enhancement of the high-speed extruded Mg alloys.

Gram-negative bacterial infections pose a significant threat to public health. Toll-like receptor 4 (TLR4) recognizes bacterial lipopolysaccharide (LPS) and induces innate immune responses, autophagy, and cell death, which have major impacts on the body’s physiological homeostasis. However, the role of TLR4 in bacterial LPS-induced autophagy and apoptosis in large mammals, which are closer to humans than rodents in many physiological characteristics, remains unknown. So far, few reports focus on the relationship between TLR, autophagy, and apoptosis in large mammal levels, and we urgently need more tools to further explore their crosstalk. Here, we generated a TLR4-enriched mammal model (sheep) and found that a high-dose LPS treatment blocked autophagic degradation and caused strong innate immune responses and severe apoptosis in monocytes/macrophages of transgenic offspring. Excessive accumulation of autophagosomes/autolysosomes might contribute to LPS-induced apoptosis in monocytes/macrophages of transgenic animals. Further study demonstrated that inhibiting TLR4 downstream NF-κB or p38 MAPK signaling pathways reversed the LPS-induced autophagy activity and apoptosis. These results indicate that the elevated TLR4 aggravates LPS-induced monocytes/macrophages apoptosis by leading to lysosomal dysfunction and impaired autophagic flux, which is associated with TLR4 downstream NF-κB and MAPK signaling pathways. This study provides a novel TLR4-enriched mammal model to study its potential effects on autophagy activity, inflammation, oxidative stress, and cell death. These findings also enrich the biological functions of TLR4 and provide powerful evidence for bacterial infection.

Recilia dorsalis is a notorious rice pest that harbors numerous symbiotic microorganisms. However, the structure and dynamics of bacterial communities in various tissues of R. dorsalis throughout its life cycle remain unclear. In this study, we used high-throughput sequencing technology to analyze the bacterial communities in the digestive, excretory, and reproductive systems of R. dorsalis at different developmental stages. The results showed that the initial microbiota in R. dorsalis mostly originated from vertical transmission via the ovaries. After the second-instar nymphs, the diversity of bacterial communities in the salivary gland and Malpighian tubules gradually decreased, while the midgut remained stable. Principal coordinate analysis revealed that the structure of bacterial communities in R. dorsalis was primarily influenced by the developmental stage, with minimal variation in bacterial species among different tissues but significant variation in bacterial abundance. Tistrella was the most abundant bacterial genus in most developmental stages, followed by Pantoea. The core bacterial community in R. dorsalis continuously enriched throughout development and contributed primarily to food digestion and nutrient supply. Overall, our study enriches our knowledge of the bacterial community associated with R. dorsalis and provides clues for developing potential biological control technologies against this rice pest.

The effect of the quenching rate after solution treatment on the residual stress and precipitation behavior of a high strength Mg-5Zn-3.5Sn-1Mn-0.5Ca-0.5Cu plate is studied. The simulation results show decreasing temperature gradient in the plate with decreasing quenching rate, which leads to weakened inhomogeneous plastic deformation and decreased residual stress. No dynamic precipitation on the grain boundary happens after either cold water cooling or air cooling, however, air cooling leads to dynamic precipitation of Mg-Zn phase on Mn particles around which a low-density precipitate zone develops after aging treatment. Moreover, the fine and densely distributed Mg-Zn precipitates observed after aging treatment of the cold water cooled alloy are replaced by coarse precipitates with low density for the air cooled alloy. Both the low-density precipitate zone near Mn particles and the coarsening of precipitates are the source of the decrease in hardness and tensile properties of the air cooled alloy. The residual stress drops faster than the hardness with decreasing quenching rate, which makes it possible to lower the residual stress without sacrificing too much age-hardening ability of the alloy.

Abstract Background Acute kidney injury (AKI) occurs among patients with coronavirus disease-19 (COVID-19) and has also been indicated to be associated with in-hospital mortality. Remdesivir has been authorized for the treatment of COVID-19. We conducted a systematic review to evaluate the incidence of AKI in hospitalized COVID-19 patients. The incidence of AKI in different subgroups was also investigated. Methods A thorough search was performed to find relevant studies in PubMed, Web of Science, medRxiv and EMBASE from 1 Jan 2020 until 1 June 2020. The systematic review was performed using the meta package in R (4.0.1). Results A total of 16,199 COVID-19 patients were included in our systematic review. The pooled estimated incidence of AKI in all hospitalized COVID-19 patients was 10.0% (95% CI: 7.0–12.0%). The pooled estimated proportion of COVID-19 patients who needed continuous renal replacement therapy (CRRT) was 4% (95% CI: 3–6%). According to our subgroup analysis, the incidence of AKI could be associated with age, disease severity and ethnicity. The incidence of AKI in hospitalized COVID-19 patients being treated with remdesivir was 7% (95% CI: 3–13%) in a total of 5 studies. Conclusion We found that AKI was not rare in hospitalized COVID-19 patients. The incidence of AKI could be associated with age, disease severity and ethnicity. Remdesivir probably did not induce AKI in COVID-19 patients. Our systematic review provides evidence that AKI might be closely associated with SARS-CoV-2 infection, which should be investigated in future studies.

Nitrogen is a crucial element for the growth and development of insects, but herbivorous insects often suffer from nitrogen nutrition deficiencies in their diets. Some symbiotic microorganisms can provide insect hosts with nitrogen nutrition through nitrogen fixation. Extensive research has clearly demonstrated the process of nitrogen fixation by symbiotic microorganisms in termites, while evidence supporting the occurrence and significance of nitrogen fixation in the diets of the Hemiptera is less conclusive. In this study, we isolated a strain of R. electrica from the digestive tract of a leafhopper, R. dorsalis, and found that it had nitrogen-fixing capabilities. Fluorescence in situ hybridization results showed that it was located in the gut of the leafhopper. Genome sequencing revealed that R. electrica possessed all the genes required for nitrogen fixation. We further evaluated the growth rate of R. electrica in nitrogen-containing and nitrogen-free media and measured its nitrogenase activity through an acetylene reduction assay. The findings of these studies could shed light on how gut microbes contribute to our understanding of nitrogen fixation.

In order to understand the effects of drawing velocity, initial grain size and texture on the microstructure evolution during directional annealing, a cellular automata model based on grain boundary (GB) curvature, GB energy and GB mobility was established with a modified calculation model of the GB curvature. The simulation results show that there is a lower limit and an upper limit to the drawing velocity for the formation of columnar grains, and the columnar grains can only be formed between the upper limit and the lower limit. The simulation results are consistent with the experimental results. When the drawing velocity is lower than the lower limit, the equiaxed grains grow at the front of the hot zone, which hinders the formation of the columnar grains. With the increase of initial grain size, the driving force of GB migration decreases, and the grain boundaries are difficult to move with the hot zone, which is not conducive to the formation of columnar grains. There is an upper limit of initial grain size for the formation of columnar grains. The abnormal growth induced by texture prevents the growth of columnar grains during directional annealing. The weaker the texture strength, the more conducive to the growth of columnar grains.

Charitable donations are an altruistic behavior whereby individuals donate money or other resources to benefit others while the recipient is normally absent from the context. Several psychological factors have been shown to influence charitable donations, including a cost-benefit analysis, the motivation to engage in altruistic behavior, and the perceived psychological benefits of donation. Recent work has identified the ventral medial prefrontal cortex (MPFC) for assigning value to options in social decision making tasks, with other regions involved in empathy and emotion contributing input to the value computation (e.g. Hare et al., 2010; Hutcherson et al., 2015; Tusche et al., 2016). Most impressively, multivariate pattern analysis (MVPA) has been applied to fMRI data to predict donation behavior on a trial-by-trial basis from ventral MPFC activity (Hare et al., 2010) while identifying the contribution of emotional processing in other regions to the value computation (e.g. Tusche et al., 2016). MVPA of EEG data may be able to provide further insight into the timing and scalp topography of neural activity related to both value computation and emotional effects on donation behavior. We examined the effect of incidental emotional states and the perceived urgency of the charitable cause on donation behavior using support vector regression on EEG data to predict donation amount on a trial by trial basis. We used positive, negative, and neutral pictures to induce incidental emotional states in participants before they made donation decisions concerning two types of charities. One category of charity was oriented toward saving people from current suffering, and the other was to prevent future suffering. Behaviorally, subjects donated more money in a negative emotional state relative to other emotional states, and more money to alleviate current over future suffering. The data-driven multivariate pattern analysis revealed that the electrophysiological activity elicited by both emotion-priming pictures and charity cues could predict the variation in donation magnitude on a trial-by-trial basis.

Pathogenic infections have badly affected public health and the development of the breeding industry. Billions of dollars are spent every year fighting against these pathogens. The immune cells of a host produce reactive oxygen species and reactive nitrogen species which promote the clearance of these microbes. In addition, autophagy, which is considered an effective method to promote the destruction of pathogens, is involved in pathological processes. As research continues, the interplay between autophagy and nitroxidative stress has become apparent. Autophagy is always intertwined with nitroxidative stress. Autophagy regulates nitroxidative stress to maintain homeostasis within an appropriate range. Intracellular oxidation, in turn, is a strong inducer of autophagy. Toll-like receptor 4 (TLR4) is a pattern recognition receptor mainly involved in the regulation of inflammation during infectious diseases. Several studies have suggested that TLR4 is also a key regulator of autophagy and nitroxidative stress. In this review, we describe the role of TLR4 in autophagy and oxidation, and focus on its function in influencing autophagy-nitroxidative stress interactions.

Abstract Background Emerging evidence has demonstrated that acute kidney injury (AKI) is an important risk factor associated with increased morbidity and mortality in diabetic ketoacidosis (DKA) patients. The current study aimed to investigate the incidence rate, risk factors, long-term renal outcomes, and mortality in DKA patients with AKI. Methods A total of 179 patients diagnosed with DKA at Sun Yat-sen Memorial Hospital from January 2012 to January 2018 were included in the analysis. AKI was diagnosed according to the 2012 KDIGO criteria. Risk factors, long-term renal outcomes, and mortality were analyzed by logistic regression and Cox proportional hazards models. Results Among 179 DKA patients, 98 patients (54.75%) were diagnosed as AKI. Aging; increased blood glucose, serum uric acid and white blood cells; decreased serum pH and albumin; coma; and preexisting chronic kidney disease (CKD) were risk factors of AKI in patients with DKA. During follow-up, DKA patients with AKI showed more than a two-fold decline in eGFR within 1 year after discharge from the hospital when compared with non-AKI DKA patients. Furthermore, AKI was also an independent risk factor for poor long-term renal outcomes and mortality in DKA patients. Conclusions Multiple risk factors contribute to the development of AKI in DKA patients. AKI and advanced AKI stage are associated with rapid progressive CKD and long-term mortality in patients with DKA.

Leakage inductance is one of the key parameters of a transformer, and it is often intentionally integrated into transformers. Rogowski’s equation is generally used for leakage inductance calculation; however, it is only applicable to concentric winding transformers where windings have the same height. Consequently, it has limited applications. This paper proposes a transformer leakage inductance calculation method using a double Fourier series. The limitation of Rogowski’s leakage inductance equation was analyzed in practical applications, and a new model for calculating the leakage inductance of a double-group-overlapping winding transformer was derived. Experimental prototypes of transformers were developed, and their simulation models were built in Ansys. The correctness of the proposed calculation method for transformer leakage inductance using a double Fourier series was verified by comparing the calculation results with the simulation and measured ones. A sensitivity analysis was also conducted by studying the variations in different parameters that might affect the leakage inductance value. The proposed calculation model gives an intuitive and simple method with less calculation and design effort while maintaining reasonable accuracy for leakage inductance calculation. In addition, the featured double Fourier series approach has a wider range of applications than Rogowski’s equation.

Aims: The effect of the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril-valsartan in patients with heart failure with preserved ejection fraction (HFpEF) remains unclear, and data on ARNI treatment in peritoneal dialysis (PD) patients are lacking. The present study was designed to assess the efficacy and safety of sacubitril-valsartan in patients with HFpEF undergoing peritoneal dialysis.Methods and Results: End-stage kidney disease (ESKD) patients undergoing PD for 3 months with New York Heart Association (NYHA) class II–IV heart failure, ejection fraction of 50% or higher, and elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP) were assigned to receive sacubitril-valsartan. Patients were followed up regularly after medication treatment. The alterations in clinical and biochemical parameters before and after taking sacubitril-valsartan (generally 50–100 mg b.i.d) were investigated, and safety was also assessed. Twenty-one patients were recruited in this study. Compared with baseline levels, NT-proBNP levels [9769.0 (3093.5–21941.0) vs. 3034.0 (1493.2–6503.0), P = 0.002], and heart rate [80.0 (74.5–90.5) vs. 75.0 (70.3–87.0), P = 0.031] were markedly decreased after treatment with sacubitril-valsartan. Signs and symptoms of heart failure (21/21 vs. 15/21, P = 0.021) were obviously alleviated, NYHA classification and E/e' ratio showed a notable trend of improvement after 3–12 months of follow-up. None of the patients showed adverse drug reactions.Conclusions: The present data suggested that sacubitril-valsartan treatment in patients with HFpEF undergoing PD was effective and safe.

As a new genetic engineering technology, gene editing can precisely modify the specific gene sequence of the organism’s genome. In the last 10 years, with the rapid development of gene editing technology, zinc-finger nucleases (ZFNs), transcription activator-like endonucleases (TALENs), and CRISPR/Cas9 systems have been applied to modify endogenous genes in organisms accurately. Now, gene editing technology has been used in mice, zebrafish, pigs, cattle, goats, sheep, rabbits, monkeys, and other species. Breeding for disease-resistance in agricultural animals tends to be a difficult task for traditional breeding, but gene editing technology has made this easier. In this work, we overview the development and application of gene editing technology in the resistance breeding of livestock. Also, we further discuss the prospects and outlooks of gene editing technology in disease-resistance breeding.

Background/Aims: The herbal medicine Kudingcha has a bitter taste and low bioavailability for lipid reduction. To improve the bioavailability and ameliorate the compliance, we prepared Kudingcha nanoparticles and investigated their effect in hyperlipidaemic rats. In addition, the safety and lipid-lowering mechanism of the Kudingcha nanoparticles were examined. Methods: Kudingcha nanoparticles were prepared by ionotropic gelation and spray-drying. Seventy rats were randomly assigned into eight groups: a normal fat diet group (NF), a high-fat group (HF), a spontaneous recovery group (SR), a Kudingcha group (KDC), a blank nanoparticle group (B-N), and a Kudingcha nanoparticle groups (low, medium and high doses). All groups (except for the normal fat diet group) were fed a high-fat diet to establish hyperlipidaemia. Different interventions were administered to the treatment groups for four weeks. Serum lipids were measured using commercially available kits according to the recommended protocols. Liver morphology and histopathology were examined by a light microscope. The mRNA and protein levels of TLR4 and NF-κB were determined by RT-PCR and Western blotting, respectively. In addition, acute toxicity was evaluated by the LD50 test. Results: The Kudingcha nanoparticles were spherical and had a smooth surface. The size distribution of the nanoparticles was 100-600 nm. Acute toxicity results revealed that the Kudingcha nanoparticles were a non-toxic substance. Compared with regular Kudingcha, TG and TC decreased distinctly in the Kudingcha nanoparticles, especially for the moderate and high dose groups (p

In the present work, the effect of heat treatment on the cyclic deformation behavior of as-extruded ZA81M magnesium alloy was investigated. Two heat treatment conditions were applied to the as-extruded ZA81M alloy: a solution treatment (T4, 653 K for 40 h and quenched with 298 K water) and a solution treatment plus artificial aging (T6, 348 K for 32 h (pre-aging at low temperature) and 453 K for 8 h (the second aging) and quenched with 353 K water). The results showed that the fine second phase precipitated after the aging treatment, the tensile yield strength of the T6-treated specimens increased, and the stress amplitude of T6-treated specimens was always higher than that of T4-treated specimens. The T6-treated specimens had a higher total strain energy density and a shorter fatigue life at a strain amplitude of 0.4%, and a lower total strain energy density and a longer fatigue life at a strain amplitude of 0.8%, compared to the T4-treated specimens. All fatigue cracks of the T4 and T6 ZA81M alloy were initiated at the second phase or along the grain boundary and propagated perpendicular to the loading direction.

Land surface temperature (LST) is an essential parameter widely used in environmental studies. The Medium Resolution Spectral Imager II (MERSI-II) boarded on the second generation Chinese polar-orbiting meteorological satellite, Fengyun-3D (FY-3D), provides a new opportunity for LST retrieval at a spatial resolution of 250 m that is higher than that of the already widely used Moderate Resolution Imaging Spectrometer (MODIS) LST data of 1000 m. However, there is no operational LST product from FY-3D MERSI-II data available for free access. Therefore, in this study, we developed an improved two-factor split-window algorithm (TFSWA) of LST retrieval from this data source as it has two thermal-infrared (TIR) bands. The essential coefficients of the TFSWA algorithm have been carefully and precisely estimated for the FY-3D MERSI-II TIR thermal bands. A new approach for estimating land surface emissivity has been developed using the ASTER Global Emissivity Database (ASTER GED) and the International Geosphere-Biosphere Program (IGBP) data. A model to estimate the atmospheric water vapor content (AWVC) from the three atmospheric water vapor absorption bands (bands 16, 17, and 18) has been developed as AWVC has been recognized as the most important factor determining the variation of AT. Using MODTRAN 5.2, the equations for the AT estimate from the retrieved AWVC were established. In addition, the AT of the pixels at the far edge of FY-3D MERSI-II data may be strongly affected by the increase of the optical path. Viewing zenith angle (VZA) correction equations were proposed in the study to correct this effect on AT estimation. Field data from four stations were applied to validate the improved TFSWA in the study. Cross-validation with MODIS LST (MYD11) was also conducted to evaluate the improved TFSWA. The cross-validation result indicates that the FY-3D MERSI-II LST from the improved TFSWA are comparable with MODIS LST while the correlation coefficients between FY-3D MERSI-II LST and MODIS LST over the Mid-East China region are in the range of 0.84~0.98 for different seasons and land cover types. Validation with 318 field LST samples indicates that the average MAE and R2 of the scenes at the four stations are about 1.97 K and 0.98, respectively. Thus, it could be concluded that the improved TFSWA developed in the study can be a good algorithm for LST retrieval from FY-3D MERSI-II data with acceptable accuracy.

Objective: To compare the efficacy and safety between laparoscopy and local injection with absolute ethanol (AE) for treating tubal ectopic pregnancy (EP). Study design: Retrospective cohort study of ectopic pregnancies in the fallopian tube from two tertiary hospitals between January 2015 and December 2017. Clinical information such as presenting symptoms, reproductive history, possible risk factors, initial diagnosis, serum beta-human chor-ionic gonadotropin (β-HCG) level, transvaginal ultrasonography findings, methods of treatment and outcomes were reviewed and analyzed. Results: A total of 119 patients were identified for this study. The diagnosis was based on clinical manifestations, ultrasonography scan and dynamic serum β-HCG. 71.4% of women (85/119) had at least one risk factor for ectopic pregnancy, with the most common risk factors being a history of induced labor, uterine curettage, spontaneous abortion or tubal pregnancy. 64 patients were managed by laparoscopic surgery (Group A) and 2 subjects were failure and followed by a systemic methotrexate (MTX) prescription. The other 55 patients had local injection with absolute ethanol, of which 9 cases failed, followed by a second local injection and intramuscular MTX. The HCG decrease rate post absolute ethanol injection was a value predictive factor for prognosis. Moreover, the pregnancy rate one-year post treatment in local injection subjects (10/55, 18.2%) was higher than that of surgical subjects (5/64, 7.8%). Conclusion: Local injection of absolute ethanol and laparoscopic surgery for tubal ectopic pregnancy are both effective and relatively safe, but laparoscopic surgery has better efficacy and shorten hospitalization day. Local injection may be less invasiveness and thus beneficial to fertility preservation. Keywords: Tubal ectopic pregnancy, Laparoscopic surgery, Local injection

Understanding how humanity’s influence on the climate affects rainfall seasonality around the world is immensely important for agriculture production, ecology protection, and freshwater resource management. In this study, we qualitatively and quantitatively analyzed the potential influence of anthropogenic forcing on rainfall seasonality in global land monsoon (GM) regions using the Coupled Model Intercomparison Project Phase 5 (CMIP5) general circulation models. We discovered that anthropogenic forcing enhances rainfall seasonality over many parts of GM regions, and was evident in the South Asian and the most parts of the South American and the South African monsoon regions. Anthropogenic forcing partially but clearly contributed to the increasing trend of rainfall seasonality over many parts of GM regions from 1960 to 2012. Moreover, anthropogenic forcing also increased the probability of more pronounced rainfall seasonality in almost all GM regions. The results provide valuable information for agriculture, ecology, and freshwater resource management under climate warming induced by anthropogenic forcing.

Some aporphine alkaloids, such as crebanine, were found to present arrhythmic activity and also higher toxicity. A series of derivatives were synthesized by using three kinds of aporphine alkaloids (crebanine, isocorydine, and stephanine) as lead compounds. Chemical methods, including ring-opening reaction, bromination, methylation, acetylation, quaternization, and dehydrogenation, were adopted. Nineteen target derivatives were evaluated for their antiarrhythmic potential in the mouse model of ventricular fibrillation (VF), induced by CHCl3, and five of the derivatives were investigated further in the rat model of arrhythmia, induced by BaCl2. Meanwhile, preliminary structure-activity/toxicity relationship analyses were carried out. Significantly, N-acetamidesecocrebanine (1d), three bromo-substituted products of crebanine (2a, 2b, 2c), N-methylcrebanine (2d), and dehydrostephanine (4a) displayed antiarrhythmic effects in the CHCl3-induced model. Among them, 7.5 mg/kg of 2b was able to significantly reduce the incidence of VF induced by CHCl3 (p < 0.05), increase the number of rats that resumed sinus rhythm from arrhythmia, induced by BaCl2 (p < 0.01), and the number of rats that maintained sinus rhythm for more than 20 min (p < 0.01). Therefore, 2b showed remarkably higher antiarrhythmic activity and a lower toxicity (LD50 = 59.62 mg/kg, mice), simultaneously, indicating that 2b could be considered as a promising candidate in the treatment of arrhythmia. Structural-activity analysis suggested that variationsin antiarrhythmic efficacy and toxicity of aporphines were related to the C-1,C-2-methylenedioxy group on ring A, restricted ring B structural conformation, N-quaternization of ring B, levoduction of 6a in ring C, and the 8-, 9-, 10-methoxy groups on ring D on the skeleton.

Adipose tissue, an indispensable organ, fulfils the pivotal role of energy storage and metabolism and is instrumental in maintaining the dynamic equilibrium of energy and health of the organism. Adipocyte hypertrophy and adipocyte hyperplasia (adipogenesis) are the two primary mechanisms of fat deposition. Mature adipocytes are obtained by differentiating mesenchymal stem cells into preadipocytes and redifferentiation. However, the mechanisms orchestrating adipogenesis remain unclear. Autophagy, an alternative cell death pathway that sustains intracellular energy homeostasis through the degradation of cellular components, is implicated in regulating adipogenesis. Furthermore, adipose tissue functions as an endocrine organ, producing various cytokines, and certain inflammatory factors, in turn, modulate autophagy and adipogenesis. Additionally, autophagy influences intracellular redox homeostasis by regulating reactive oxygen species, which play pivotal roles in adipogenesis. There is a growing interest in exploring the involvement of autophagy, inflammation, and oxidative stress in adipogenesis. The present manuscript reviews the impact of autophagy, oxidative stress, and inflammation on the regulation of adipogenesis and, for the first time, discusses their interactions during adipogenesis. An integrated analysis of the role of autophagy, inflammation and oxidative stress will contribute to elucidating the mechanisms of adipogenesis and expediting the exploration of molecular targets for treating obesity-related metabolic disorders. [ABSTRACT FROM AUTHOR]

[Objectives] Some Chinese medicinal materials of Jianjin Zhuanggu Paste were microscopically identified, and several active ingredients were studied by thin-layer identification, which provides reference for further improving the quality standards of hospital preparations. [Methods] The effective components of Jianjin Zhuanggu Paste were qualitatively identified by thin-layer chromatography (TLC). [Results] The microscopic identification of the three Chinese medicinal materials in Jianjin Zhuanggu Pate showed the microscopic characteristics of Radix Codonopsis, Radix Astragali and Radix Notoginseng. TLC identification showed that there were characteristic spots of Radix Codonopsis, Radix Astragali, Radix Rehmanniae Preparata and Radix Notoginseng in Jianjin Zhuanggu Paste. [Conclusions] This study established the quality standard research method of Jianjin Zhuanggu Paste, which further strengthens the safety standards of hospital preparations, and improves the clinical efficacy of drugs, as well as the quality standards of hospital preparations to a certain extent. [ABSTRACT FROM AUTHOR]