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Objective: We aimed to investigate the prognostic factors of pediatric extracorporeal cardiopulmonary resuscitation (ECPR)., Methods: The retrospective study included a total of 77 pediatric cases (7 neonates and 70 children) who underwent ECPR after in-hospital and out-of-hospital cardiac arrest between July 2007 and December 2022. Primary endpoints were complications, while secondary endpoints included all-cause in-hospital mortality., Results: Among the 45 cases experiencing complications, 4 neonates and 41 children had multiple simultaneous complications, primarily neurological issues in 25 cases. Additionally, organ failure occurred in 11 cases, and immunodeficiency was present in two cases. Furthermore, 9 cases experienced bleeding events, and 13 cases showed thrombosis. Patients with complications had lower weight, shorter ECMO durations, and longer CPR durations. Non-survivors had longer CPR durations and shorter durations of ECMO, ICU stay, and mechanical ventilation compared to survivors. Complications were more prevalent in non-survivors, particularly organ failure and bleeding events., Conclusion: Weight, CPR duration, and ECMO duration were associated with complications, suggesting areas for treatment optimization. The higher occurrence of complications in non-survivors underscores the importance of early detection and management to improve survival rates. Our findings suggest clinicians consider these factors in prognostic assessments to enhance the effectiveness of ECPR programs., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aspergillus flavus contamination in agriculture and food industries poses threats to human health, leading to a requirement of a safe and effective method to control fungal contamination. Chitosan-based nitrogen-containing derivatives have attracted much attention due to their safety and enhanced antimicrobial applications. Herein, a new benzimidazole-grafted chitosan (BAC) was synthesized by linking the chitosan (CS) with a simple benzimidazole compound, 2-benzimidazolepropionic acid (BA). The characterization of BAC was confirmed by Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance spectroscopy ( 1 H and 13 C NMR). Then, the efficiency of BAC against A. flavus ACCC 32656 was investigated in terms of spore germination, mycelial growth, and aflatoxin production. BAC showed a much better antifungal effect than CS and BA. The minimum inhibitory concentration (MIC) value was 1.25 mg/mL for BAC, while the highest solubility of CS (16.0 mg/mL) or BA (4.0 mg/mL) could not completely inhibit the growth of A. flavus . Furthermore, results showed that BAC inhibited spore germination and elongation by affecting ergosterol biosynthesis and the cell membrane integrity, leading to the permeabilization of the plasma membrane and leakage of intracellular content. The production of aflatoxin was also inhibited when treated with BAC. These findings indicate that benzimidazole-derived natural CS has the potential to be used as an ideal antifungal agent for food preservation.

In this study, we investigated the photo-catalytic mechanisms for the construction of C-O bonds from arenes (benzene, 2',6'-dimethyl-[1,1'-biphenyl]-2-carboxylic acid, or 2,4-dichloro-1-fluorobenzene), catalyzed by 2,3-dichloro-5,6-dicyano- p -benzoquinone (DDQ). All the structures for the Gibbs free surfaces were calculated at the M06-2X-D3/ma-def2-SVP level in the SMD solvent model. Also, TDDFT calculations of DDQ were performed at the PBE1PBE-D3/ma-def2-SVP level in the SMD solvent model. The computational results indicated that DDQ, serving as a photo-catalyst, would be excited under visible light of 450 nm, aligning well with experimental observations as reflected in the UV-vis spectrum. Gibbs free energy surface analyses of the three reactions suggested that the path involving 3 DDQ* activating the reactant (-COOH, H 2 O, or CH 3 OH) is favorable. Additionally, the role of O 2 was investigated, revealing that it could facilitate the recycling of DDQ by lowering the energy barrier for the conversion of the DDQH˙ radical (not DDQH 2 ) into DDQ. The use of ρ hole and ρ ele can reveal the photo-catalytic reaction and charge transfer processes, while localized orbital locator isosurfaces and electron spin density isosurface graphs were employed to analyze structures and elucidate the single electron distribution. These computational results offer valuable insights into the studied interactions and related processes, shedding light on the mechanisms governing C-O bond formation from arenes catalyzed by DDQ.

Plant stomatal phenotype traits play an important role in improving crop water use efficiency, stress resistance and yield. However, at present, the acquisition of phenotype traits mainly relies on manual measurement, which is time-consuming and laborious. In order to obtain high-throughput stomatal phenotype traits, we proposed a real-time recognition network SLPA-Net for stomata localization and phenotypic analysis. After locating and identifying stomatal density data, ellipse fitting is used to automatically obtain phenotype data such as apertures. Aiming at the problems of small stomata and high similarity to background, we introduced ECANet to improve the accuracy of stoma and aperture location. In order to effectively alleviate the unbalance problem in bounding box regression, we replaced the Loss function with a more effective Focal EIoU Loss. The experimental results show that SLPA-Net has excellent performance in the migration generalization and robustness of stomata and apertures detection and identification, as well as the correlation between stomata phenotype data obtained and artificial data.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Host cell invasion is mediated by the interaction of the viral spike protein (S) with human angiotensin-converting enzyme 2 (ACE2) through the receptor-binding domain (RBD). In this work, bio-layer interferometry (BLI) was used to screen a series of fifty-two peroxides, including aminoperoxides and bridged 1,2,4 - trioxolanes (ozonides), with the aim of identifying small molecules that interfere with the RBD-ACE2 interaction. We found that two compounds, compound 21 and 29, exhibit the activity to inhibit RBD-ACE2. They are further demonstrated to inhibit SARS-CoV-2 cell entry, as shown in pseudovirus assay and experiment with authentic SARS-CoV-2. A comprehensive in silico analysis was carried out to study the physicochemical and pharmacokinetic properties, revealing that both compounds have good physicochemical properties as well as good bioavailability. Our results highlight the potential of small molecules targeting RBD inhibitors as potential therapeutic drugs for COVID-19., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Importance: Gaining insight into the cell-entry mechanisms of swine acute diarrhea syndrome coronavirus (SADS-CoV) is critical for investigating potential cross-species infections. Here, we demonstrated that pretreatment of host cells with tunicamycin decreased SADS-CoV attachment efficiency, indicating that N-linked glycosylation of host cells was involved in SADS-CoV entry. Common N-linked sugars Neu5Gc and Neu5Ac did not interact with the SADS-CoV S1 protein, suggesting that these molecules were not involved in SADS-CoV entry. Additionally, various host proteases participated in SADS-CoV entry into diverse cells with different efficiencies. Our findings suggested that SADS-CoV may exploit multiple pathways to enter cells, providing insights into intervention strategies targeting the cell entry of this virus., Competing Interests: The authors declare no conflict of interest.

Background: ALKBH5 belongs to the ALKB family consists of a Fe (II) and a-ketoglutarate-dependent dioxygenase. ALKBH5 directly catalyzes the oxidative demethylation of m6A-methylated adenosine. ALKBH5 involves in tumorigenesis and tumor progression, and is often dysregulated in a wide range of cancers, including colorectal cancer. Emerging evidence indicates that the expression of ALKBH5 is associated with the abundance of infiltrating immune cells in the microenvironment. However, how ALKBH5 affects immune cell infiltration in the microenvironment in colorectal cancer (CRC) has not been reported. The aim of this study was to identify how the expression of ALKBH5 affects the biological behaviors of CRC cell lines and regulates the effects on infiltrating CD8 + T cells in CRC microenvironment with its specific mechanism., Methods: Firstly, the transcriptional expression profiles of CRC were downloaded from TCGA database and integrated via R software (4.1.2). Between CRC and normal colorectal tissues, ALKBH5 mRNA expressions were compared (Wilcoxon rank-sum). We further identified the expression levels of ALKBH5 in CRC tissues and cell lines through quantitative PCR, western blot, and immunohistochemistry. Then, how ALKBH5 affects the biological behaviors of CRC cells were confirmed by gain- and loss-of-function analysis. Furthermore, the relationship between ALKBH5 level and 22 tumor-infiltrating immune cells was examined through CIBERSORT in R software. Furthermore, we explored the correlation between ALKBH5 expression and tumor-infiltrated CD8 + , CD4 + and regulatory T cells by utilizing the TIMER database. Finally, the association between chemokines and CD8 + T cells infiltration in CRC was analyzed using GEPIA online database. qRT-PCR, WB and IHC were used to further determine the effect of ALKBH5 on NF-κB-CCL5 signaling axis and CD8 + T cells infiltration., Results: Clinically, ALKBH5 expression was downregulated in CRC and low levels of ALKBH5 expression were correlated with poor overall survival (OS). Functionally, overexpression of ALKBH5 reduced the proliferation, migration and invasion of CRC cells, and vice versa. Overexpression of ALKBH5 suppresses NF-κB pathway, thus reduces CCL5 expression and promotes CD8 + T cells infiltration in CRC microenvironment., Conclusions: ALKBH5 is poorly expressed in CRC, and overexpression of ALKBH5 attenuates CRC malignant progression by inhibiting CRC cell proliferation, migration, invasion and promoting CD8 + T cells infiltration in the tumor microenvironment through NF-κB-CCL5 axis., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant-induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA., (© 2023. The Author(s).)

Objectives: To study the effect of ligustrazine injection on mitophagy in neonatal rats with hypoxic-ischemic encephalopathy (HIE) and its molecular mechanism., Methods: Neonatal Sprague-Dawley rats, aged 7 days, were randomly divided into a sham-operation group with 8 rats, a model group with 12 rats, and a ligustrazine group with 12 rats. The rats in the model group and the ligustrazine group were used to establish a neonatal rat model of HIE by ligation of the left common carotid artery followed by hypoxia treatment, and blood vessels were exposed without any other treatment for the rats in the sham-operation group. The rats in the ligustrazine group were intraperitoneally injected with ligustrazine (20 mg/kg) daily after hypoxia-ischemia, and those in the sham-operation group and the model group were intraperitoneally injected with an equal volume of normal saline daily. Samples were collected after 7 days of treatment. Hematoxylin and eosin staining and Nissl staining were used to observe the pathological changes of neurons in brain tissue; immunohistochemical staining was used to observe the positive expression of PINK1 and Parkin in the hippocampus and cortex; TUNEL staining was used to measure neuronal apoptosis; Western blotting was used to measure the expression levels of the mitophagy pathway proteins PINK1 and Parkin and the autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and ubiquitin-binding protein (P62)., Results: Compared with the sham-operation group, the model group had a significant reduction in the number of neurons, an increase in intercellular space, loose arrangement, lipid vacuolization, and a reduction in Nissl bodies. The increased positive expression of PINK1 and Parkin, apoptosis rate of neurons, and protein expression levels of PINK1, Parkin, Beclin1 and LC3 ( P <0.05) and the decreased protein expression level of P62 in the hippocampus were also observed in the model group ( P <0.05). Compared with the model group, the ligustrazine group had a significant increase in the number of neurons with ordered arrangement and an increase in Nissl bodies, significant reductions in the positive expression of PINK1 and Parkin, the apoptosis rate of neurons, and the protein expression levels of PINK1, Parkin, Beclin1, and LC3 ( P <0.05), and a significant increase in the protein expression level of P62 ( P <0.05)., Conclusions: Ligustrazine can alleviate hypoxic-ischemic brain damage and inhibit neuronal apoptosis in neonatal rats to a certain extent, possibly by inhibiting PINK1/Parkin-mediated autophagy.

The purpose of this study was to determine the diagnostic efficacy of Xpert MTB/RIF assay for rapid diagnosis of Tuberculosis (TB) and detection of rifampicin (RIF) resistance in patients suspected of having EPTB, assessing it against traditional culture and drug susceptibility test (DST) by proportional method, and the ability to predict multidrug resistance TB by Xpert MTB/RIF assay. In this study, the Xpert MTB/RIF assay was applied to 1,614 extrapulmonary specimens. Compared with TB culture and Composite Reference Standard (CRS), the Xpert MTB/RIF assay had a high sensitivity and specificity for detection of EPTB. Depending on the culture method or CRS as the standard, sensitivity of the Xpert MTB/RIF assay for detection of MTB in pleural effusion, cerebrospinal fluid, thoracic drainage fluid and throat swabs specimens were lower than that of other specimens. According to the experimental results, we have reason to believe that Xpert MTB/RIF assay is a rapid and simple technique with high sensitivity and specificity for diagnosing EPTB and detecting drug resistance in variety of specimens. Xpert MTB/RIF assay combined with DST maybe identify more cases of multi-drug resistant tuberculosis (MDR-TB)., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Oxalate oxidase is an enzyme that degrades oxalate and is used in commercial urinary assays to measure oxalate levels. The objective of this study was to establish an enhanced expression system for secretion and purification of oxalate oxidase using Pichia pastoris. A codon optimized synthetic oxalate oxidase gene derived from Hordeum vulgare (barley) was generated and cloned into the pPICZα expression vector downstream of the N-terminal alpha factor secretion signal peptide sequence and used for expression in P. pastoris X-33 strain. A novel chimeric signal peptide consisting of the pre-OST1 sequence fused to pro-αpp8 containing several amino acid substitutions was also generated to enhance secretion. Active enzyme was purified to greater than 90% purity using Q-Sepharose anion exchange chromatography. The purified oxalate oxidase enzyme had an estimated Km value of 256μM, and activity was determined to be 10U/mg. We have developed an enhanced oxalate oxidase expression system and method for purification., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Donelan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ethnopharmacological Relevance: Inadequate trophoblasts migration and invasion is considered as an initial event resulting in preeclampsia, which is closely related to oxidative stress. Berberine hydrochloride (BBR), extracted from the traditional medicinal plant Coptis chinensis Franch., exerts a diversity of pharmacological effects, and the crude drug has been widely taken by most Chinese women to treat nausea and vomit during pregnancy. But there is no research regarding its effects on trophoblast cell function., Aim of the Study: This study aimed to investigate the effect of BBR on human-trophoblast-derived cell line (HTR-8/SVneo) migration ability and its mechanism., Materials and Methods: Cell viability was detected by CCK-8 assay. The effect of BBR on cells migration function was examined by scratch wound healing assay and transwell migration assay. Intracellular nitric oxide (NO), superoxide (O 2 - ) and peroxynitrite (ONOO - ) levels were measured by flow cytometry. The expression levels of inducible NO synthase (iNOS), eNOS, p-eNOS, MnSOD, CuZnSOD, Rac1, NOX1, TLR4, nuclear factor-κB (NF-κB), p-NFκB, pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in cells were analyzed by Western blotting. Uric acid sodium salt (UA), the scavenger of ONOO - , PEG-SOD (a specific superoxide scavenger), L-NAME (a NOS inhibitor) and antioxidants (Vit E and DFO) were further used to characterize the pathway of BBR action., Results: 5 μM BBR decreased both the migration distance and the number of migrated cells without affecting cells viability in HTR-8/SVneo cells after 24 h treatment. BBR could increase the level of NO in HTR-8/SVneo cells, and the over-production of NO might be attributable to iNOS, but not eNOS. BBR could increase intracellular O 2 - levels, and the over-production of O 2 - is closely related with Rac1 in HTR-8/SVneo cells. The excessive production of NO and O 2 - further react to form ONOO - , and the increased ONOO - level induced by BBR was blunted by UA. Moreover, UA improved the impaired migration function caused by BBR in HTR-8/SVneo cells. The depressed migration function stimulated by BBR in HTR-8/SVneo cells was diminished by PEG-SOD and L-NAME. Furthermore, BBR increased the expression of IL-6 in HTR-8/SVneo cells, and antioxidants (Vit E and DFO) could decrease the expression of IL-6 and iNOS induced by BBR., Conclusions: BBR inhibits the cell migration ability through increasing inducible NO synthase and peroxynitrite in HTR-8/SVneo cells, indicating that BBR and traditional Chinese medicines containing a high proportion of BBR should be used with caution in pregnant women., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Congenital systemic candidiasis is a rare disease observed in both full-term and preterm infants. It can occur with or without congenital cutaneous candidiasis (CCC) and to date, only a few cases have been reported in the literature. We report here, a case of a full-term newborn who presented with diffuse skin eruptions at birth. Blood, urine, and skin scraping cultures were positive and the aetiological agent was Candida albicans . After six weeks of anti-fungal treatment with fluconazole, the newborn was cured. Early diagnosis is crucial in preventing complications caused by candidiasis in newborns.

Objective: To investigate the effect of myrislignan (MYR) on the apoptosis of gastric cancer cell line and its relationship with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway., Methods: The gastric cells (SGC-7901) were treated with MYR at different concentrations, i.e., 0, 25, 50, 100, and 200 μmol/L, for 48 h and 72 h and the effect of MYR on the proliferation of SGC-7901 cells was measured by CCK-8 assay. Then, SGC-7901 cells were treated with different concentrations of MYR at 50, 100, and 200 μmol/L for 48 h. Meanwhile, a normal control group and a dimethyl sulfoxide (DMSO) solvent control group (0.1% DMSO) were established. Flow cytometry was used to determine the apoptosis rate of SGC-7901 cells. The protein expression levels of PI3K, AKT, Bcl-2-associated X protein (BAX), cysteine-dependent aspartate-specifc protease-3 (Caspase-3), and Caspase-9 were determined by Western blot. Then, PI3K activator (20 μmol/mL) was used to treat SGC-7901 cells for 48 h in 4 groups, the control group, 0.1% DMSO group, MYR group, and MYR+PI3K activator group, and the effect on MYR's induction of apoptosis and regulation of the protein expression levels of PI3K, AKT, BAX, Caspase-3, and Caspase-9 in SGC-7901 cells., Results: Compared with the control group, MYR at 50, 100 and 200 μmol/L inhibited the proliferation of gastric cancer cells, increased the apoptosis rate, down-regulated the protein expression levels of PI3K and AKT, and up-regulated the protein expression levels of BAX, Caspase-3, and Caspase-9 in a dose-dependent manner ( P <0.05). However, PI3K activator attenuated MYR-induced apoptosis in gastric cancer cells and MYR's regulation of PI3K, AKT, BAX, Caspase-3, and Caspase-9 protein expression ( P <0.05)., Conclusion: MYR induces the expression of BAX, Caspase-3, and Caspase-9 proteins by inhibiting the PI3K/AKT signaling pathway, thereby promoting the apoptosis of gastric cancer cells., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Four undescribed bisbenzylisoquinoline alkaloids, designated as Stephtetrandrine A-D, were isolated from the roots of Stephania tetrandra . Their structures were elucidated by IR, HRESIMS, ECD spectra, 1 D and 2 D NMR spectra and comparison with the literature data. Additional five known compounds (limacine, tetrandrine, N - trans -Feruloyltyramine, 2'-N-chloromethyltetrandrine, 2,2'-N-N-dichloromethyltetrandrine) were also isolated. N - trans -Feruloyltyramine was isolated from Stephania tetrandra for the first time. The isolated compounds were tested for monoamine oxidase, acetylcholinesterase, phosphoinositide 3-kinase α and human hepatoma cell HepG2 inhibitory activities. Stephtetrandrine C showed obvious inhibitory effect on human hepatoma HepG2, with IC 50 value of 16.2 μM. Limacine and 2'-N-chloromethyltetrandrine showed moderate monoamine oxidase inhibitory effect with the IC 50 values of 37.7 and 29.2 μM, respectively.

It is of great clinical significance to develop potential novel strategies to prevent diabetic cardiovascular complications. Endothelial progenitor cell (EPC) dysfunction is a key contributor to diabetic vascular complications. In the present study we evaluated whether low-dose nifedipine could rescue impaired EPC-mediated angiogenesis and prevent cardiovascular complications in diabetic mice. Diabetes was induced in mice by five consecutive injections of streptozotocin (STZ, 60 mg·kg -1 ·d -1 , i.p.). Diabetic mice were treated with low-dose nifedipine (1.5 mg·kg -1 ·d -1 , i.g.) for six weeks. Then, circulating EPCs in the peripheral blood were quantified, and bone marrow-derived EPCs (BM-EPCs) were prepared. We showed that administration of low-dose nifedipine significantly increased circulating EPCs, improved BM-EPCs function, promoted angiogenesis, and reduced the cerebral ischemic injury in diabetic mice. Furthermore, we found that low-dose nifedipine significantly increased endothelial nitric oxide synthase (eNOS) expression and intracellular NO levels, and decreased the levels of intracellular O 2 .- and thrombospondin-1/2 (TSP-1/2, a potent angiogenesis inhibitor) in BM-EPCs of diabetic mice. In cultured BM-EPCs, co-treatment with nifedipine (0.1, 1 μM) dose-dependently protected against high-glucose-induced impairment of migration, and suppressed high-glucose-induced TSP-1 secretion and superoxide overproduction. In mice with middle cerebral artery occlusion, intravenous injection of diabetic BM-EPCs treated with nifedipine displayed a greater ability to promote local angiogenesis and reduce cerebral ischemic injury compared to injection of diabetic BM-EPCs treated with vehicle, and the donor-derived BM-EPCs homed to the recipient ischemic brain. In conclusion, low-dose nifedipine can enhance EPCs' angiogenic potential and protect against cerebral ischemic injury in diabetic mice. It is implied that chronic treatment with low-dose nifedipine may be a safe and economic manner to prevent ischemic diseases (including stroke) in diabetes., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: To investigate neuroprotective effects of total saponins from Trillium tschonoskii Maxim (TST) on vascular cognitive impairment (VCI) rats through inflammatory body of the NOD-like body protein 3 (NLRP3) regulated by endoplasmic reticulum stress (ERS). Methods: SD rats were divided into sham-operated group (SHAM), model group (VCI, bilateral neck arterial ligation (BCCAO) method), TST intervention group (TST, 100 mg/kg), and positive group (donepezil hydrochloride, 0.45 mg/kg ), continuous administration for 4 weeks. The ability of learning and memory was evaluated by the morris water labor. The tissue pathological changes were observed by HE and NISSL staining. Western blot was used to detectendoplasmic reticulum-related proteins GRP78, IRE1, XBP1. Inflammasome-related proteins NLRP3, ASC, Caspase-1, IL-18, IL-1β. Results: Compared with the SHAM group, the escape latency of VCI group rats was prolonged significantly, and the number of times of crossing the platform and the percentage of target quadrant residence time were shortened ( P ＜0.01); The cells in the hippocampus of VCI rats were damaged, with obvious pyknosis, decreased number of neurons and damage of cell body structure; The endoplasmic reticulum and inflammatory corpuscle-associated proteins were increased in VCI group ( P ＜0.05 or P ＜0.01). Compared with the VCI group, the TST group and the positive group had less time to search for the platform, and the ratio of the times of crossing the platform to the time in the target quadrant was longer ( P ＜0.05 or P ＜0.01). There was no significant difference in the times of crossing the platform between the positive group and VCI group ( P ＞0.05); The cell damage, nuclear pyknosis and the number of neurons in TST and positive groups were significantly reduced; The endoplasmic reticulum associated proteins and inflammatory body associated proteins in TST group and positive group were decreased to different degrees ( P ＜0.05 or P ＜0.01). Conclusion: TST has neuroprotective effects on VCI rats, and its mechanism may be related to the involvement of ERS in the regulation of NLRP3 inflammatory small bodies.

Starch is an ideal wall material for controlled release in oral delivery systems due to its non-allergic properties, availability, and cheap price. However, because of its poor mechanical behavior and high water permeability, it is necessary to modify the amphiphilic nature of starch. Surfactants are essential components to emulsify the lyophobic food ingredients. However, the interaction of starch with emulsifiers and how they affect the pasting behavior and digestion of starch are not well understood. In this paper, surfactants, such as non-ionic Tween (TW) and ionic sodium fatty acid (NaFA), with varying hydrophobic carbon chain lengths, were selected as model amphiphiles to investigate the structural, pasting, rheological properties and in vitro digestibility of regular and frozen starch samples. The results showed that, in most cases, the addition of TW reduced the viscosity of starch. However, saturated medium-chain NaFA increased the starch viscosity and rheological modulus greatly. Both surfactants inhibited starch digestion. This paper presents a comparative investigation on the effect of ionic and non-ionic surfactant on the structure and properties of corn starch, and therefore the information is useful for structural-based formulation with starch for developing colloidal delivery systems. It is also helpful for developing functional food with controllable digestion properties.

The mechanism of host cell invasion of severe acute respiratory syndrome coronavirus-2 SARS-CoV-2 is connected with the interaction of spike protein (S) with angiotensin-converting enzyme 2 (ACE2) through receptor-binding domain (RBD). Small molecules targeting this assembly are being investigated as drug candidates to contrast SARS-CoV-2. In this context, chloroquine, an antimalarial agent proposed as a repurposed drug to treat coronavirus disease-19 (COVID-19), was hypothesized to bind RBD among its other mechanisms. Similarly, artemisinin and its derivatives are being studied as potential antiviral agents. In this work, we investigated the interaction of artemisinin, its metabolite dihydroartemisinin and chloroquine with RBD by means of computational tools and in vitro . Docking studies showed that the compounds interfere with the same region of the protein and molecular dynamics (MD) simulations demonstrated the stability of the predicted complexes. Bio-layer interferometry showed that chloroquine dose-dependently binds RBD (KD = 35.9 µM) more efficiently than artemisinins. [Formula: see text].

Artemisinin, isolated from the traditional Chinese medicinal plant qīng hāo ( Artemisia annua ) and its derivatives are used for treatment of malaria. With treatment failures now being recorded for the derivatives and companion drugs used in artemisinin combination therapies new drug combinations are urgently required. The amino-artemisinins artemiside and artemisone display optimal efficacies in vitro against asexual and sexual blood stages of the malaria parasite Plasmodium falciparum and are active against tumour cell lines. In continuing the evolution of combinations of the amino-artemisinins with new drugs, we examine the triterpenoid quinone methide celastrol isolated from the traditional Chinese medicinal plant léi gōng téng ( Tripterygium wilfordii ). This compound is redox active, and has attracted considerable attention because of potent biological activities against manifold targets. We report that celastrol displays good IC 50 activities ranging from 0.50-0.82 µM against drug-sensitive and resistant asexual blood stage Pf , and 1.16 and 0.28 µM respectively against immature and late stage Pf NF54 gametocytes. The combinations of celastrol with each of artemisone and methylene blue against asexual blood stage Pf are additive. Given that celastrol displays promising antitumour properties, we examined its activities alone and in combinations with amino-artemisinins against human liver HepG2 and other cell lines. IC 50 values of the amino-artemisinins and celastrol against HepG2 cancer cells ranged from 0.55-0.94 µM. Whereas the amino-artemisinins displayed notable selectivities (SI > 171) with respect to normal human hepatocytes, in contrast, celastrol displayed no selectivity (SI < 1). The combinations of celastrol with artemiside or artemisone against HepG2 cells are synergistic. Given the promise of celastrol, judiciously designed formulations or structural modifications are recommended for mitigating its toxicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ng, Han, Yang, Birkholtz, Coertzen, Wong, Haynes, Coghi and Wong.)

Phytoene desaturase (PDS) is not only an important enzyme in the biosynthesis of carotenoids but also a promising target for herbicide discovery. However, in recent years, no expected PDS inhibitors with new scaffolds have been reported. Hence, a solution for developing PDS inhibitors is to search for new compounds with novel chemotypes based on the PDS protein structure. In this work, we integrated structure-based virtual screening, structure-guided optimization, and biological evaluation to discover some PDS inhibitors with novel chemotypes. It is noteworthy that the highly potent compound 1b , 1-(4-chlorophenyl)-2-((5-(hydroxymethyl)-4-(3-(trifluoromethyl)phenyl)-4 H -1,2,4-triazol-3-yl)thio)ethan-1-one, exhibited a broader spectrum of post-emergence herbicidal activity at 375-750 g/ha against six kinds of weeds than the commercial PDS inhibitor diflufenican. Surface plasmon resonance (SPR) assay showed that the affinity of our compound 1b ( K D = 65.9 μM) to PDS is slightly weaker but at the same level as diflufenican ( K D = 38.3 μM). Meanwhile, determination of the phytoene content and PDS mRNA quantification suggested that 1b could induce PDS mRNA reduction and phytoene accumulation. Moreover, 1b also caused the increase of reactive oxygen species (ROS) and the change of ROS-associated enzyme activity in albino leaves. Hence, all these results indicated the feasibility of PDS protein structure-based virtual screen and structure optimization to search for highly potent PDS inhibitors with novel chemotypes for weed control.

Extracts from Securidaca longipedunculata showed antiplasmodial activities against reference clones and clinical isolates using SYBR Green I method. A new benzophenone, 2,3,4,5-tetramethoxybenzophenone ( 1 ) was isolated and characterized along with seven known compounds: 4-hydroxy-2,3-dimethoxybenzophenone ( 2 ); 3-hydroxy-5-methoxybiphenyl ( 3 ), methyl-2-hydroxy-6-methoxybenzoate ( 4 ), benzyl-2-hydroxy-6-methoxybenzoate ( 5 ), 2-hydroxy-6-methoxybenzoic acid ( 6 ), 2,4,5-trimethoxybenzophenone ( 7 ) and 2-methoxy-3,4-methylenedioxybenzophenone ( 8 ). Compounds 1 and 2 showed ex vivo antiplasmodial activities (IC 50 28.8 μM and 18.6 μM, respectively); while 5 and 8 showed in vivo activities (IC 50 19.7 μM and 14.5 μM, respectively) against D6 strain. In a cytotoxicity assay, all the extracts (with an exception of the MeOH extract of the leaves) and pure compounds were not toxic to the normal LO2 and BEAS cell-lines, while the methanol roots extract (IC 50 66.4 µg/mL against A549, and 77.4 µg/mL against HepG2), compounds 6 (IC 50 22.2 µM against A549) and 7 (IC 50 45.2 µM against HepG2) were weakly active against cancerous cell-lines.

Programmed necrosis,a mode of cell death independent of Caspase,is mainly mediated by receptor-interacting protein kinase-1 (RIPK1),receptor-interacting protein kinase-3 (RIPK3),and mixed lineage kinase domain-like protein (MLKL).Studies have demonstrated that programmed necrosis has the dual role of promoting and inhibiting tumor growth and thus we can control the development of tumor by regulating programmed necrosis.The drugs capable of inducing programmed necrosis show potential anti-tumor activity.In addition,inducing programmed necrosis is an effective way to overcome tumor resistance to apoptosis.This paper summarized the mechanisms of programmed necrosis and its relationship with tumors.We focused on the antitumor activity of programmed necrosis inducers including natural products,chemotherapeutic drugs,death receptor ligands,kinase inhibitors,inorganic salts,metal complexes,and metal nanoparticles.These agents will provide new therapeutic candidates for the treatment of tumors,especially the tumors acquiring resistance to apoptosis.

In this study, the antileishmanial and cytotoxic activities of secondary metabolites isolated from Tabernaemontana ventricosa Hochst. ex A. DC., Aloe tororoana Reynolds, and Aloe schweinfurthii var. labworana Reynolds were investigated. Overall, nineteen known compounds were isolated from the three plant species. The compounds were characterized based on their spectroscopic data. Voacristine and aloenin were the most active compounds against promastigotes of antimony-sensitive Leishmania donovani (IC 50 11 ± 5.2 μM and 26 ± 6.5 µM, respectively) with low toxicity against RAW264.7, murine monocyte/macrophage-like cells. The in silico docking evaluation and in vitro NO generation assay also substantially support the antileishmanial effects of these compounds. In a cytotoxicity assay against cancer and normal cell lines, ursolic acid highly inhibited proliferation of lung cancer cells, A549 (IC 50 6.61 ± 0.7 μM) while voacristine was moderately active against human liver cancer cells, HepG2 (IC 50 23.0 ± 0.0 μM). All other compounds were inactive against the test parasites and cell lines. [Formula: see text].

The rational design and preparation of advanced electrocatalysts for the hydrogen evolution reaction (HER) under alkaline conditions is the key to achieving sustainable hydrogen production. Herein, a new type of nitrogen-doped porous carbon nanosheets (NPCN) loaded with platinum group metals (Pd, Pt or Ru) were prepared. The introduction of melamine not only realized the doping of N-species, but also optimized the morphology and surface functional groups of the prepared catalysts. The prepared Pd-NPCN, Pt-NPCN and Ru-NPCN with a metal loading of about 10 wt% showed outstanding HER activity (21, 9 and 11 mv at 10 mA cm -2 current density), small Tafel slopes (49, 30 and 30 mV dec -1 ) and good stability in 1.0 M KOH. In addition, the mechanism of the introduction of melamine to improve the catalytic performance of HER was also discussed. Therefore, this work provides promising alternatives to traditional Pt-based catalysts, and is instructive for the design of high-efficiency alkaline HER catalysts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Herein, we have synthesized a series of lipophilic, halogenated-arylvinyl-1,2,4-trioxanes 8a-g (28 compounds) and assessed for their in vitro anti-plasmodial activity in Plasmodium falciparum culture using SYBRgreen-I fluorescence assay against chloroquine-resistant Pf INDO and artemisinin-resistant Pf Cam 3.1 R539T (MRA-1240) strains. Alongside, the cell cytotoxic potential of 8a-g has also been determined against the HEK293 cell line in vitro. Out of twenty-eight halogenated-arylvinyl-1,2,4-trioxanes; ten analogues (8a 2 , 8a 4 , 8b 2 , 8b 4 , 8d 4 , 8e 1 , 8e 2 , 8e 4, 8f 2 , and 8g 4 ) have shown potent in vitro antiplasmodial activity with IC 50  < 27 nM (IC 50 range = 4.48-26.58 nM). Also, the selectivity index (SI) for these ten analogues were found in the range of 72.00-3972.50 which indicates their selective potential towards Plasmodium cells. Results of the cell cycle stage specificity with two of the most potent compounds 8a 4 {(IC 50  = 4.48 nM; SI = 3972.50) more potent than chloroquine (IC 50  = 546 nM; SI = 36.64) and artesunate (IC 50  = 6.6 nM; SI = 4333.33)} and 8e 2 (IC 50  = 9.69 nM; SI = 1348) against Pf INDO indicated all three stages to be the target of the action of 8e 2 while only rings and trophozoites appeared to be targeted by 8a 4 . Ring stage survival assay against artemisinin-resistant Pf Cam 3.1 R539T indicated that 8a 4 may be well suited to replace artemisinin from current ACTs which are experiencing in vivo delayed parasite clearance. With intraperitoneal (i.p.) and oral (p.o.) route at the dose of 50 mg/kg/day × 4 days; 8a 4 has also shown 100% suppression of parasitemia in P. berghei ANKA infected Balb C mice. Further, the in vitro anticancer activity of 8a-g performed against human lung (A549) and liver (HepG2) cancer cell lines as also against immortalized normal lung (BEAS-2B) and liver (LO2) cell lines has revealed that most of the derivatives are endowed also with promising anticancer activity (IC 50  = 0.69-15 μM; SI = 1.02-20.61) in comparison with standard drugs such as chloroquine (IC 50  = 100 μM; SI = 0.03), artemisinin (IC 50  = 100 μM), and artesunic acid (IC 50  = 9.85 μM; SI = 0.76), respectively. All the derivatives have shown moderate anticancer activity against liver (HepG2) cancer cell lines. Arylvinyl-1,2,4-trioxanes 8f 2 (IC 50  = 0.69 μM; SI = 16.66), the most active compound of the series, has shown ∼145 fold more cytotoxic potential with higher selectivity in comparison to reference drugs chloroquine (IC 50  = 100 μM; SI = 0.03) and artemisinin (IC 50  = 100 μM), respectively against the lung (A549) cancer cell line. Finally, the in-silico docking studies of the potent halogenated 1,2,4-trioxanes along with reference drug molecules against epidermal growth factor receptor (EGFR; PDB ID: 1M17) have demonstrated the strong virtual interaction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

It is of great clinical significance to develop potential novel strategies to prevent cardio-cerebrovascular complications in patients with hyperlipidemia. Vascular Endothelial integrity and function play a key role in the prevention of cardio-cerebrovascular diseases. Endothelial progenitor cells (EPCs) can home to sites of ischemic injury and promote endothelial regeneration and neovascularization. Hypercholesterolemia impairs the function of EPC. The present study attempted to identify the effect of piperlongumine on EPCs' angiogenic potential and cerebral ischemic injury in high-fat diet-fed (HFD-fed) mice. Here, we showed that treatment with low-does piperlongumine (0.25 mg/kg/day) for 8 weeks significantly improved EPCs function and reduced the cerebral ischemic injury (both infarct volumes and neurobehavioral outcomes) in HFD-fed mice. In addition, low-dose piperlongumine administration increased intracellular NO level and reduced intracellular O 2 - level in EPCs of HFD-fed mice. Moreover, incubation with piperlongumine (1.0 μM, 24 h) reduced thrombospondin-1/2 (TSP-1/2, a potent angiogenesis inhibitor) expression levels in EPCs from HFD-fed mice, increased the therapeutic effect of EPC from HFD-fed mice on cerebral ischemic injury reduction and angiogenesis promotion in HFD-fed mice, and the donor derived EPCs homed to the recipient ischemic brain. In conclusion, low-dose piperlongumine can enhance EPCs' angiogenic potential and protect against cerebral ischemic injury in HFD-fed mice. It is implied that treatment with low-dose piperlongumine might be a potential option to prevent ischemic diseases (including stroke) in patients with hyperlipidemia, and priming with piperlongumine might be a feasible way to improve the efficacy of EPC-based therapy for ischemic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dong, Peng, Zhang, Jiang, Yang, He, Tao, Zhang, Chen and Xie.)

Benzo[a]pyrene (B[a]P) and polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants. The effects in organisms of exposures to binary mixtures of such contaminants remain obscure. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy is a label-free, non-destructive analytical technique allowing spectrochemical analysis of macromolecular components, and alterations thereof, within tissue samples. Herein, we employed ATR-FTIR spectroscopy to identify biomolecular changes in rat liver post-exposure to B[a]P and BDE-47 (2,2',4,4'-tetrabromodiphenyl ether) congener mixtures. Our results demonstrate that significant separation occurs between spectra of tissue samples derived from control versus exposure categories (accuracy = 87%; sensitivity = 95%; specificity = 79%). Additionally, there is significant spectral separation between exposed categories (accuracy = 91%; sensitivity = 98%; specificity = 90%). Segregation between control and all exposure categories were primarily associated with wavenumbers ranging from 1600 to 1700 cm -1 . B[a]P and BDE-47 alone, or in combination, induces liver damage in female rats. However, it is suggested that binary exposure apparently attenuates the toxic effects in rat liver of the individual contaminants. This is supported by morphological observations of liver tissue architecture on hematoxylin and eosin (H&E)-stained liver sections. Such observations highlight the difficulties in predicting the endpoint effects in target tissues of exposures to mixtures of environmental contaminants., (© 2021 John Wiley & Sons, Ltd.)

In forensic traumatic pathology practice, immunohistochemistry and special staining technique play an important role in wound age estimation and complications of traumatic complication identification. They even play an important role in the identification of special cases, such as snakebites and insulin killings. This article reviews the application and value of immunohistochemistry and special staining techniques in forensic traumatic pathology based on the cases of forensic practice reported in literature.

A new phenylpentenol, wortmannine H ( 1 ) was isolated from Talaromyces wortmannii LGT-4, an endophytic fungus of Tripterygium wilfordii . The structure of 1 was elucidated by IR, MS, 1D and 2D NMR spectra and comparison of the experimental and calculated optical rotatory dispersion (ORD). Monoamine oxidase (MAO), acetylcholinesterase (AChE) and phosphoinositide 3-kinase (PI3Kα) inhibitory activities of 1 was also tested. The compound did not show good biological activity.

Bacillus amyloliquefaciens strain EA19 is an endophyte isolated from Erigeron annuus with antifungal activity against Blumeria graminis f. sp. tritici , Magnaporthe oryzae, and Fusarium graminearum. The genome sequence of this strain is 3.96 Mb and contains 3,421 coding sequences, which will facilitate an understanding of the mechanisms of biocontrol.

Host cell invasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by the interaction of the viral spike protein (S) with human angiotensin-converting enzyme 2 (ACE2) through the receptor-binding domain (RBD). In this work, computational and experimental techniques were combined to screen antimalarial compounds from different chemical classes, with the aim of identifying small molecules interfering with the RBD-ACE2 interaction and, consequently, with cell invasion. Docking studies showed that the compounds interfere with the same region of the RBD, but different interaction patterns were noted for ACE2. Virtual screening indicated pyronaridine as the most promising RBD and ACE2 ligand, and molecular dynamics simulations confirmed the stability of the predicted complex with the RBD. Bio-layer interferometry showed that artemisone and methylene blue have a strong binding affinity for RBD (K D = 0.363 and 0.226 μM). Pyronaridine also binds RBD and ACE2 in vitro (K D = 56.8 and 51.3 μM). Overall, these three compounds inhibit the binding of RBD to ACE2 in the μM range, supporting the in silico data.

Introduction: Far-infrared radiation (FIR) is widely used in the treatment of various diseases such as insomnia and cardiovascular risk. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which the therapeutic potential of FIR in RA is unclear., Objectives: To determine the therapeutic potential and mechanistic actions of FIR in treatment of RA., Methods: Adjuvant-induced arthritis (AIA) rat models were established to assess the therapeutic potency of FIR in RA treatment. The scoring parameters such as arthritis score, swelling of the hind paw, spleen and thymus indices, micro-CT analysis indices were adopted to estimate the beneficial effects of FIR during RA treatment in AIA model. PCR gene expression arrays were used to analyze inflammatory and autoimmune genes expression profiles in rat synovium. The inflammatory and immunity genes profiling was further analyzed through transcription factor prediction using PROMO. A signaling network map of possible molecular circuits connecting the identified differential genes to the RA's pathogenesis was constructed based on extensive literature reviews, and the major signaling pathways were validated by Western blotting., Results: Thirty minutes of FIR treatment significantly improved the symptoms of AIA in rats. Gene expression profiling indicated that 27 out of 370 genes were down-regulated by FIR. AP-1, CEBPα, CEBPβ, c-Fos, GR, HNF-3β, USF-1, and USF-2 were predicted as key transcription factors that regulated the identified differential genes. In addition, MAPK, PI3K-Akt, and NF-κB signaling are the major molecular pathways down-regulated by FIR treatment., Conclusion: FIR may provide beneficial effects on the AIA rat model of arthritis by suppression of the MAPK, PI3K-Akt and NF-κB signaling pathways. Therefore, we believe that FIR may provide an alternative non-pharmacological and non-surgical therapeutic approach for the treatment of RA., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V. on behalf of Cairo University.)

The first phytochemical investigation of the flowers of Millettia dura resulted in the isolation of seven isoflavones, a flavonol and a chalcone. Eleven isoflavones and a flavonol isolated from various plant parts from this plant were tested for cytotoxicity against a panel of cell lines, and six of these showed good activity with IC 50 values of 6-14 μM. Durmillone was the most active with IC 50 values of 6.6 μM against A549 adenocarcinomic human alveolar basal epithelial cancer cell line with low cytotoxicity against the non-cancerous cell lines BEAS-2B (IC 50 = 58.4 μM), LO2 hepatocytes (IC 50 78.7 μM) and CCD19Lu fibroblasts (IC 50 >100 μM).

Background: The outbreak of coronavirus (SARS-CoV-2) disease caused more than 100,000,000 people get infected and over 2,200,000 people being killed worldwide. However, the current developed vaccines or drugs may be not effective in preventing the pandemic of COVID-19 due to the mutations of coronavirus and the severe side effects of the newly developed vaccines. Chinese herbal medicines and their active components play important antiviral activities. Corilagin exhibited antiviral effect on human immunodeficiency virus (HIV), hepatitis C virus (HCV) and Epstein-Barr virus (EBV). However, whether it blocks the interaction between SARS-CoV-2 RBD and hACE2 has not been elucidated., Purpose: To characterize an active compound, corilagin derived from Phyllanthus urinaria as potential SARS-CoV-2 entry inhibitors for its possible preventive application in daily anti-virus hygienic products., Methods: Computational docking coupled with bio-layer interferometry, BLI were adopted to screen more than 1800 natural compounds for the identification of SARS-CoV-2 spike-RBD inhibitors. Corilagin was confirmed to have a strong binding affinity with SARS-CoV-2-RBD or human ACE2 (hACE2) protein by the BLI, ELISA and immunocytochemistry (ICC) assay. Furthermore, the inhibitory effect of viral infection of corilagin was assessed by in vitro pseudovirus system. Finally, the toxicity of corilagin was examined by using MTT assay and maximal tolerated dose (MTD) studies in C57BL/6 mice., Results: Corilagin preferentially binds to a pocket that contains residues Cys 336 to Phe 374 of spike-RBD with a relatively low binding energy of -9.4 kcal/mol. BLI assay further confirmed that corilagin exhibits a relatively strong binding affinity to SARS-CoV-2-RBD and hACE2 protein. In addition, corilagin dose-dependently blocks SARS-CoV-2-RBD binding and abolishes the infectious property of RBD-pseudotyped lentivirus in hACE2 overexpressing HEK293 cells, which mimicked the entry of SARS-CoV-2 virus in human host cells. Finally, in vivo studies revealed that up to 300 mg/kg/day of corilagin was safe in C57BL/6 mice. Our findings suggest that corilagin could be a safe and potential antiviral agent against the COVID-19 acting through the blockade of the fusion of SARS-CoV-2 spike-RBD to hACE2 receptors., Conclusion: Corilagin could be considered as a safe and environmental friendly anti-SARS-CoV-2 agent for its potential preventive application in daily anti-virus hygienic products., (Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

There is still a lack of competing risk analysis of patients with papillary renal cell carcinoma (pRCC) following surgery. We performed the cumulative incidence function (CIF) to estimate the absolute risks of cancer-specific mortality (CSM) and other-cause mortality (OCM) of pRCC over time, and constructed a nomogram predicting the probability of 2-, 3- and 5-year CSM based on competing risk regression. A total of 5993 pRCC patients who underwent nephrectomy between 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The 2-, 3-, 5-year CSM rates were 3.2%, 4.4% and 6.5%, respectively, and that of OCM were 3.2%, 5.0% and 9.3%, respectively. The estimates of 5-year cumulative mortality were most pronounced among patients aged > 75 years in OCM (17.0%). On multivariable analyses, age, tumor grade, T stage, N stage, and with or without bone, liver and lung metastases were identified as independent predictors of CSM following surgery and were integrated to generate the nomogram. The nomogram achieved a satisfactory discrimination with the AUC t of 0.730 at 5-year, and the calibration curves presented impressive agreements. Taken together, age-related OCM is a significant portion of all-cause mortality in elderly patients and our nomogram can be used for decision-making and patient counselling.

The outbreak of SARS-CoV-2 virus caused more than 80,155,187 confirmed COVID-19 cases worldwide, which has posed a serious threat to global public health and the economy. The development of vaccines and discovery of novel drugs for COVID-19 are urgently needed. Although the FDA-approved SARS-CoV-2 vaccines has been launched in many countries recently, the strength of safety, stringent storage condition and the possibly short-term immunized efficacy remain as the major challenges in the popularity and recognition of using vaccines against SARS-CoV-2. With the spike-receptor binding domain (RBD) of SARS-CoV-2 being responsible for binding to human angiotensin-converting enzyme 2 receptor (hACE2), ACE2 is identified as the receptor for the entry and viral infection of SARS-CoV-2. In this study, molecular docking and biolayer interferometry (BLI) binding assay were adopted to determine the direct molecular interactions between natural small-molecule, 1,2,3,4,6-Pentagalloyl glucose (PGG) and the spike-RBD of the SARS-CoV-2. Our results showed that PGG preferentially binds to a pocket that contains residues Glu 340 to Lys 356 of spike-RBD with a relatively low binding energy of -8 kcal/mol. BLI assay further confirmed that PGG exhibits a relatively strong binding affinity to SARS-CoV-2-RBD protein in comparison to hACE2. In addition, both ELISA and immunocytochemistry assay proved that PGG blocks SARS-CoV-2-RBD binding to hACE2 dose dependently in cellular level. Notably, PGG was confirmed to abolish the infectious property of RBD-pseudotyped lentivirus in hACE2 overexpressing HEK293 cells, which mimicked the entry of wild type SARS-CoV-2 virus in human host cells. Finally, maximal tolerated dose (MTD) studies revealed that up to 200 mg/kg/day of PGG was confirmed orally safe in mice. Our findings suggest that PGG may be a safe and potential antiviral agent against the COVID-19 by blockade the fusion of SARS-CoV-2 spike-RBD to hACE2 receptors. Therefore, PGG may be considered as a safe and natural antiviral agent for its possible preventive application in daily anti-virus hygienic products such as a disinfectant spray or face mask., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Yang, Hamdoun, Chung, Lam, Zhang, Guo, Xia, Law and Wong.)

Five known compounds (1-5) were isolated from the extract of Mundulea sericea leaves. Similar investigation of the roots of this plant afforded an additional three known compounds (6-8). The structures were elucidated using NMR spectroscopic and mass spectrometric analyses. The absolute configuration of 1 was established using ECD spectroscopy. In an antiplasmodial activity assay, compound 1 showed good activity with an IC 50 of 2.0 μM against chloroquine-resistant W2, and 6.6 μM against the chloroquine-sensitive 3D7 strains of Plasmodium falciparum. Some of the compounds were also tested for antileishmanial activity. Dehydrolupinifolinol (2) and sericetin (5) were active against drug-sensitive Leishmania donovani (MHOM/IN/83/AG83) with IC 50 values of 9.0 and 5.0 μM, respectively. In a cytotoxicity assay, lupinifolin (3) showed significant activity on BEAS-2B (IC 50 4.9 μM) and HePG2 (IC 50 10.8 μM) human cell lines. All the other compounds showed low cytotoxicity (IC 50  > 30 μM) against human lung adenocarcinoma cells (A549), human liver cancer cells (HepG2), lung/bronchus cells (epithelial virus transformed) (BEAS-2B) and immortal human hepatocytes (LO2)., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cancer stem cells (CSCs), responsible for cancer metastasis and recurrence, are generated from non-CSCs after chemo-radiation therapy. This study investigated the induction of CSC potential in non-stem breast cancer cells and the underlying molecular mechanisms in detachment culture., Methods: Bulk breast cancer cells, or sorted non-CSCs and CSCs were cultured under an attached or detached condition to assess CSC numbers, ability to form tumor spheres, expression of stemness markers, and chemoresistance. Lentivirus carrying CD147 shRNA or cDNA was used to manipulate CD147 expression, while CD147 ligand recombinant cyclophilin A (CyPA) or its inhibitor was used to activate or inhibit CD147 signaling., Results: Detachment promoted anoikis resistance, chemoresistance, sphere formation, self-renewal, and expression of stemness markers in breast cancer cells. Detachment increased functional ALDH + or CD44 high CD24 -/ low CSCs, and induced CSC potential in ALDH - or CD44 low CD24 high non-CSCs. Upon detachment, both CD147 expression and CyPA secretion were enhanced, and CyPA-CD147 activation mediated detachment induced CSC potential in non-CSCs via STAT3 signaling. Clinically, CD147 and pSTAT3 were highly co-expressed and correlated with poor overall survival and tumor recurrence in breast cancer patients., Conclusion: This study demonstrates that detachment induces the generation of CSCs from non-stem breast cancer cells via CyPA-CD147 signaling, indicating that targeting CD147 may serve as a potential novel therapeutic strategy for lethal metastatic breast cancer by eliminating induced CSCs., (Copyright © 2020 Meng, Fan, Yang, Xu, He, Xu, Wu, Wang, Cui, Wang, Wang, Wu, Jiang, Xu, Chen and Li.)

Two new compounds Talaromycin A ( 1 ) and Talaromycin B ( 2 ) were isolated from a liquid culture of Talaromyces aurantiacus. The structures of 1 and 2 were elucidated by IR, MS, 1D and 2D NMR spectra and comparison of the experimental and calculated electronic circular dichroism spectra. Additional known compounds ( 3-6 ) were also isolated. These compounds were tested for monoamine oxidase, acetylcholinesterase and PI3K inhibitory activity, but showed only weak activity.

Dendritic cells (DCs) are the most important antigen-presenting cells that determine cancer immune responses by regulating immune activation and tolerance, especially in the initiation stage of specific responses. Manipulation of DCs to enhance specific antitumor immune response is considered to be a powerful tool for tumor eradication. Nanotechnology, which can incorporate multifunction components and show spatiotemporal control properties, is of great interest and is widely investigated for its ability to improve immune response activity against cancer and even for prevention and avoiding recurrence. In this mini-review, we aim to provide a general view of DC-based immunotherapy, including that involving the promising nanotechnology. Particularly we discuss: (1) manipulation or engineering of DCs for adoptive vaccination, (2) employing DCs as a combination to more existing therapeutics in tumor treatment, and (3) direct modulation of DCs in vivo to enhance antigen presentation efficacy and priming T cells subsequently. We comprehensively discuss the updates on the application of nanotechnology in DC-based immunotherapy and provide some insights on the challenges and opportunities of DC-based immunotherapeutics, including the potential of nanotechnology, against cancers., (Copyright © 2020 Qian, Yang and Cui.)

Langerhans cell sarcoma (LCS) is a rare, malignant neoplastic disorder of Langerhans cells thought to arise from antecedent Langerhans cell histiocytosis (LCH) or de novo . There are less than 70 cases of LCS reported in the medical literature, with this case being the first report of primary vulvar LCS. We present the case of a 73-year-old female with a painful 2 cm ulcerated lesion of the right labia majora. The patient was treated with oral antibiotics without resolution. On referral to gynecologic oncology an office biopsy showed LCS. Surgical excision was performed with clear margins and diagnostic confirmation of LCS by histopathological features and immunohistochemical evaluation. The patient received adjuvant radiation therapy (45.6 Gy). After 33 months of surveillance, the patient remains with no evidence of disease. Due to the rarity of this disease, there is a lack of standardized recommendations for adjuvant therapy, including radiotherapy and chemotherapy regimens for both localized and systemic LCS. This case report supports the management of localized disease by surgical excision followed by radiotherapy as effective for preventing recurrence and metastatic progression. Early recognition and treatment are critical for cure, and can be accomplished by prompt referral to a specialist as well as low threshold for biopsy. Further investigation is needed for establishing a standardized management guideline for LCS., Competing Interests: The authors declared that there is no conflict of interest., (© 2020 The Author(s).)

Institute of Materials, Chinese Academy of Engineering Physics, Jiangyou 621908, P. R. China To improve the stability of organic-inorganic hybrid perovskite, cesium-containing methylammonium lead iodide perovskite have been synthesized by one-step solution deposition. With the increasing of Cs + doping concentration, direct optical band gap of perovskite was increases, while defects and roughness of perovskite thin films were gradually augmented. A certain amount of Cs + incorporated in perovskite absorb layer could improve power conversion efficiency through the enhancing of open circuit voltage and fill factor. However, excessive Cs + doping concentration results in the reduced of short-circuit current and fill factor, which reduced power conversion efficiency. The optimized ratio 10% Cs + doping achieved the highest power conversion efficiency (16.84%).

Hollow Li₄Ti 5 O 12 nanotubes were synthesized by stirring in a heated oil bath using P25 as titanium source and lithium hydroxide as lithium source. The as-prepared samples displayed a nanotube structure, with diameter of about 20~50 nm and length of 0.4 μ m. The specific surface area of as-prepared samples reached 153.2 m²g -1 . It is demonstrated that the Li₄Ti 5 O 12 nanotubes with improved performance can be obtained by hollow structure and high specific surface area. In consequence, it delivered a high reversible initial discharge capacity of 174.2 mAh g -1 at 0.5 C rate. A stable capacity of 170.9 mAh g -1 was delivered when the rate was reduced back to 0.5 C, suggesting good structural stability of the nanocable, high reversibility even after high rate charge- discharge, and good cycle stability. In addition, a capacity of 134.9 mAh g -1 and 98 mAhg -1 could be retained at a high rate of 5 C and 10 C, indicating excellent rate performances.

Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1 PBD was confirmed using fluorescence polarization and microscale thermophoresis. This compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cells revealed that MCC1019 induced cell growth inhibition through inactivation of AKT signaling pathway, it also induced prolonged mitotic arrest-a phenomenon known as mitotic catastrophe, which is followed by immediate cell death via apoptosis and necroptosis. MCC1019 significantly inhibited tumor growth in vivo in a murine lung cancer model without affecting body weight or vital organ size, and reduced the growth of metastatic lesions in the lung. We propose MCC1019 as promising anti-cancer drug candidate., (© 2019 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

In the present study, nine compounds (1-9) were isolated from Colletotrichum gloeosporioides (an endophytic fungus from Uncaria rhynchophylla) which was cultured in wheat bran medium. Their structures were elucidated as 4-Epi-14-hydroxy-10, 23-dihydro-24, 25-dehydroaflavinine (1), 10, 23-Dihydro-24,25 -dehydro-21-oxoaflavinine (2), Ergosterol (3), Ergosterol peroxide (4), Mellein (5), 4, 5-dihydroblumenol A (6), Colletotrichine A (7), Cyclo(L-leucyl-L-leucyl) (8), and Brevianamide F (9) based on NMR spectral data, as well as comparing with previous literature data. This is the first report about the isolation of compounds 1-2, 6, and 8-9 from Colletotrichum genus. All compounds were tested for their phosphoinositide 3-kinase (PI3Kα) inhibitory activity. Compounds 8 and 9 showed potent PI3K α inhibitory activity with IC 50 values of 38.1 and 4.8 µM, respectively, while the other compounds showed very weak activity at a concentration of 20 µg/mL.

BACKGROUND This study aimed to investigate the factors associated with sarcopenia in elderly residents in three nursing homes in Suzhou City, East China including the association with nutrition and physical exercise. MATERIAL AND METHODS Elderly residents (n=316) from three nursing homes included 112 men and 204 women. The appendicular skeletal muscle index (ASMI), grip strength, and movements were measured to diagnose sarcopenia. The correlation between sarcopenia with age, sex, body mass index (BMI), ASMI, upper arm circumference, calf circumference, muscle content, grip strength, dietary intake, degree and duration of movement were also assessed. RESULTS The prevalence of sarcopenia was 28.8% (30.4% for men and 27.9% for women). Patients with sarcopenia were older compared with controls. Height, BMI, upper arm circumference, calf circumference and arm muscle mass, lower limb muscle mass, limb skeletal muscle index and ASMI, grip strength, and pace of movement were lower than controls. The prevalence of sarcopenia correlated with the intake of meat, fish, eggs, and milk, and duration of weekly aerobic and resistance exercise. Logistic regression analysis showed a positive correlation between the prevalence of sarcopenia and age, and a negative correlation between BMI and consumption of meat, eggs, and milk. CONCLUSIONS The prevalence of sarcopenia in elderly residents in three nursing homes in Suzhou City was 28.8%. Increasing age was a risk factor for sarcopenia. Increased BMI and a diet containing meat, eggs, and milk were protective factors. The findings from this study provide support that adequate dietary protein can prevent sarcopenia in the elderly.