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Necroptosis‐mediated cell death is an important mechanism in intracerebral hemorrhage (ICH)‐induced secondary brain injury (SBI). Our previous study has demonstrated that receptor‐interacting protein 1 (RIP1) mediated necroptosis in SBI after ICH. However, further mechanisms, such as the roles of receptor‐interacting protein 3 (RIP3), mixed lineage kinase domain‐like protein (MLKL), and Ca2+/calmodulin‐dependent protein kinase II (CaMK II), remain unclear. We hypothesized that RIP3, MLKL, and CaMK II might participate in necroptosis after ICH, including their phosphorylation. The ICH model was induced by autologous blood injection. First, we found the activation of necroptosis after ICH in brain tissues surrounding the hematoma (propidium iodide staining). Meanwhile, the phosphorylation and expression of RIP3, MLKL, and CaMK II were differently up‐regulated (western blotting and immunofluorescent staining). The specific inhibitors could suppress RIP3, MLKL, and CaMK II (GSK'872 for RIP3, necrosulfonamide for MLKL, and KN‐93 for CaMK II). We found the necroptosis surrounding the hematoma and the concrete interactions in RIP3‐MLKL/RIP3‐CaMK II also both decreased after the specific intervention (co‐immunoprecipitation). Then we conducted the short‐/long‐term neurobehavioral tests, and the rats with specific inhibition mostly had better performance. We also found less blood–brain barrier (BBB) injury, and less neuron loss (Nissl staining) in intervention groups, which supported the neurobehavioral tests. Besides, oxidative stress and inflammation were also alleviated with intervention, which had significant less reactive oxygen species (ROS), tumor necrosis factor (TNF)‐α, lactate dehydrogenase (LDH), Iba1, and GFAP surrounding the hematoma. These results confirmed that RIP3‐phosphorylated MLKL and CaMK II participate in ICH‐induced necroptosis and could provide potential targets for the treatment of ICH patients. [ABSTRACT FROM AUTHOR]

Polymeric micelles are widely used as multifunctional drug carriers of poorly water‐soluble drugs, but the role of drug loading content is often overlooked. The purpose of this study is to investigate the cellular uptake and penetration of polymeric micelles with different drug loading contents and their effects on biological activities. In this study, poly(N‐(2‐hydroxypropyl) methacrylamide‐co‐methacrylic acid)‐block‐poly methyl methacrylate P(HPMA‐co‐MAA)‐b‐PMMA micelles are used as a nanocarrier for the encapsulation of the potent anticancer agent ellipticine (EPT). The micelles are loaded with various amounts of EPT and the physicochemical characteristics such as particle size, morphology, and zeta potential of blank and EPT loaded nanoparticles are studied. Moreover, fluorescent lifetime studies confirm that hydrophobic EPT is indeed in the PMMA micelle core. In vitro cytotoxicity tests using the glioma cell line U87MG reveal lower IC50 values when the cells are incubated with micelle with high drug loading content. The higher toxicity in micelles with higher drug loading content is associated with higher cellular uptake, which is monitored using laser scanning confocal microscopy and flow cytometry. Moreover, higher activity of micelles with higher drug loading is also observed in U87MG multicellular tumor spheroids although the difference is not significant. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Lung cancer is the most prevalent malignancy in adults. Circular RNA (circRNA) circCPA4 (hsa_circ_0082374) is highly expressed in non‐small cell lung cancer (NSCLC). The purpose of this study was to explore the role and mechanism of circCPA4 in lung cancer.CircCPA4, linear CPA4, TGF‐β‐induced factor homeobox 2 (TGIF2), and microRNA‐214‐3p (miR‐214‐3p) levels were measured by real‐time quantitative polymerase chain reaction (RT‐qPCR). The protein levels of TGIF2, Beclin1, and p62 were assessed by western blot assay. Colony numbers, migration, invasion, apoptosis, and cell cycle progression were examined by colony formation, wound‐healing, transwell, and flow cytometry assays, respectively. The binding relationship between miR‐214‐3p and circCPA4 or TGIF2 was predicted by StarBase or TargetScan and then verified by a dual‐luciferase reporter, RNA immunoprecipitation (RIP), and RNA pulldown assays. The biological role of circCPA4 on lung tumor growth was assessed by a xenograft tumor model in vivo, and TGIF2 and ki‐67 expression was assessed by immunohistochemistry.We determined that CircCPA4 and TGIF2 were increased, and miR‐214‐3p was decreased in lung cancer tissues and cells. Functionally, circCPA4 knockdown could suppress colony formation, migration, invasion, cell cycle progression, and expedite apoptosis of lung cancer cells in vitro. Mechanically, circCPA4 could regulate TGIF2 expression by sponging miR‐214‐3p. In addition, circCPA4 deficiency inhibited the tumor growth in lung cancer in the mouse model.CircCPA4 could act as a sponge of miR‐214‐3p to upregulate TGIF2 expression, thereby promoting the progression of lung cancer cells. These findings suggested underlying therapeutic targets for the treatment of lung cancer. [ABSTRACT FROM AUTHOR]

MXene‐based thermal camouflage materials have gained increasing attention due to their low emissivity, however, the poor anti‐oxidation restricts their potential applications under complex environments. Various modification methods and strategies, e.g., the addition of antioxidant molecules and fillers have been developed to overcome this, but the realization of long‐term, reliable thermal camouflage using MXene network (coating) with excellent comprehensive performance remains a great challenge. Here, a MXene‐based hybrid network comodified with hyaluronic acid (HA) and hyperbranched polysiloxane (HSi) molecules is designed and fabricated. Notably, the presence of appreciated HA molecules restricts the oxidation of MXene sheets without altering infrared stealth performance, superior to other water‐soluble polymers; while the HSi molecules can act as efficient cross‐linking agents to generate strong interactions between MXene sheets and HA molecules. The optimized MXene/HA/HSi composites exhibit excellent mechanical flexibility (folded into crane structure), good water/solvent resistance, and long‐term stable thermal camouflage capability (with low infrared emissivity of ≈0.29). The long‐term thermal camouflage reliability (≈8 months) under various outdoor weathers and the scalable coating capability of the MXene‐coated textile enable them to disguise the IR signal of various targets in complex environments, indicating the great promise of achieved material for thermal camouflage, IR stealth, and counter surveillance. [ABSTRACT FROM AUTHOR]

The formation of a non‐specific protein corona around nanoparticles (NPs) has been identified as one of the culprits for failed nanomedicine. The amount and type of adsorbed protein from the blood plasma are known to determine the fate of NPs and the accessibility of targeting ligands. Herein, we show that the adsorbed protein may not only enlarge the NPs and change their surface properties but also, in the case of soft NPs such as polymer micelles, lead to deformation. Poly(1‐O‐methacryloyl ‐β‐D‐fructopyranose)‐b‐poly(methylmethacrylate) (P(1‐O‐MAFru)‐b‐PMMA) block co‐polymers were self‐assembled into NPs with a spherical core–shell morphology as determined by small angle neutron scattering (SANS). Upon incubation with albumin, TEM, SANS, and small angle X‐ray scattering (SAXS) revealed the adsorption of albumin and deformation of the NPs with a spheroid geometry. Removal of the protein led to the reversal of the morphology back to the spherical core–shell structure. Structural studies and cell studies of uptake of the NPs imply that the observed deformation may influence blood circulation time and cell uptake. [ABSTRACT FROM AUTHOR]

The formation of a non‐specific protein corona around nanoparticles (NPs) has been identified as one of the culprits for failed nanomedicine. The amount and type of adsorbed protein from the blood plasma are known to determine the fate of NPs and the accessibility of targeting ligands. Herein, we show that the adsorbed protein may not only enlarge the NPs and change their surface properties but also, in the case of soft NPs such as polymer micelles, lead to deformation. Poly(1‐O‐methacryloyl ‐β‐D‐fructopyranose)‐b‐poly(methylmethacrylate) (P(1‐O‐MAFru)‐b‐PMMA) block co‐polymers were self‐assembled into NPs with a spherical core–shell morphology as determined by small angle neutron scattering (SANS). Upon incubation with albumin, TEM, SANS, and small angle X‐ray scattering (SAXS) revealed the adsorption of albumin and deformation of the NPs with a spheroid geometry. Removal of the protein led to the reversal of the morphology back to the spherical core–shell structure. Structural studies and cell studies of uptake of the NPs imply that the observed deformation may influence blood circulation time and cell uptake. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC), a subclass of neck and head cancers, is the predominant cause of cancer‐associated death globally. LncRNA MAGI2‐AS3 has been previously reported to be associated with multiple cancers, but its molecular mechanism in NPC has not been fully explained. Hence, the purpose of this study is to identify the role and regulatory mechanism of MAGI2‐AS3 in NPC. Methods: Reverse‐transcription quantitative polymerase chain reaction (RT‐qPCR) and Western blot (WB) were employed to examine gene levels. The biologic function of MAGI2‐AS3 in NPC was estimated by cell counting, EdU, Transwell, and WB assays. Luciferase reporter and radioimmunoprecipitation (RIP) assays were carried out to determine the combination between miR‐218‐5p and MAGI2‐AS3, GDPD5, and SEC61A1. Results: MAGI2‐AS3 is expressed at a high level in NPC cell lines. Moreover, MAGI2‐AS3 knockdown‐suppressed NPC progression in vitro and in vivo. Furthermore, MAGI2‐AS3 functioned as a competing endogenous RNA (ceRNA) by sponging miR‐218‐5p to increase the expression of GDPD5 in NPC. Importantly, it was found that MAGI2‐AS3 regulated NPC progression and cisplatin resistance via modulating GDPD5. In addition, MAGI2‐AS3 could also promote the proliferation and migration in NPC cells by regulating SEC61A1. Conclusion: MAGI2‐AS3/miR‐218‐5p/GDPD5/SEC61A1 axis drove cell proliferation, migration, and epithelial‐mesenchymal transition, and conferred cisplatin resistance in NPC, which may provide a novel insight into the development of NPC. [ABSTRACT FROM AUTHOR]

Background: China is an ageing society, with around 150 million people aged 60 years or older. The prevalence of dementia will increase by more than 100% in the coming 20 years. This study aimed to investigate the prevalence and effects of dementia among the community elderly in Chongqing, China. Methods: Cluster sampling was adopted. A sample of elderly individuals aged 60 years and older was extracted as research subjects from three counties within Chongqing, China. One‐on‐one interviews were conducted through a general information questionnaire, and the Mini‐Mental State Examination, Instrumental Activity of Daily Living Scale, and Geriatric Depression Scale were administered. The investigated data were tested by χ2, and the effect factors of dementia were analyzed by multiple logistic regression analysis. Statistical significance was set at P < 0.05. Results: We distributed 1850 questionnaire, and the response rate was 100%. However, only 1781 questionnaires were able to be used in the study. Of the 1781 elderly respondents, 186 (10.44%) presented with dementia. Our findings revealed that differences in regions, age, marital status, education level, occupation, tobacco consumption, alcohol consumption, freshwater fish consumption, exercise, intensive labour, mah‐jong‐ and chess‐playing habits, media consumption (i.e. watching TV, listening to the radio, or reading the newspaper), body mass index, hypertension, coronary heart disease, and depression were statistically significant in the prevalence of dementia (P < 0.05). Conclusions: According to multiple logistic regression analyses, living in a rural area, older age, being single, obesity, hypertension, coronary heart disease, and depression are risk factors for dementia. In contrast, cessation of smoking, freshwater fish consumption, moderate or frequent exercise, intensive labour, daily housework, outdoor activities, media consumption, and social activities are protective factors against dementia among community elderly in Chongqing, China. [ABSTRACT FROM AUTHOR]

Abstract: A fast, sensitive, and reliable ultra‐high performance liquid chromatography coupled with tandem mass spectrometry method has been developed and validated for simultaneous quantification of geniposide, polygalaxanthone III, 3,6′‐disinapoyl sucrose, α‐asarone, β‐asarone, poricoic acid A, poricoic acid B, dehydrotumulosic acid, deoxyschizandrin, schizandrin B, and kaempferide in plasma after oral administration of extracts of Jia‐Wei‐Kai‐Xin‐San in normal and vascular dementia rats. The developed method was precise and accurate within the linearity range of the analytes. The lower limits of quantification were 1.04–2.68 ng/mL for all the analytes. Both intra‐ and inter day precision and accuracy of the analytes were all within accepted criteria. The mean extraction recoveries of the analytes and the internal standard from rat plasma were all >60.0%. The validated method had been successfully applied to compare pharmacokinetic profiles of the analytes in plasma of normal and vascular dementia rat treated with herbal extracts. Results indicated that differences existed between normal and vascular dementia model rats except dehydrotumulosic acid and kaempferide, which might be due to the pathology of vascular dementia and pharmacological effect of the analytes. These pharmacokinetic studies might benefit for the mechanism exploration and clinical use of traditional Chinese medicine formulae. [ABSTRACT FROM AUTHOR]

GATA3 is a key transcription factor in cell fate determination and its dysregulation has been implicated in various types of malignancies. However, how the abundance and function of GATA3 are regulated remains unclear. Here, we report that GATA3 is physically associated with FBXW7α, and FBXW7α destabilizes GATA3 through assembly of a SKP1-CUL1-F-box E3 ligase complex. Importantly, we showed that FBXW7α promotes GATA3 ubiquitination and degradation in a GSK3 dependent manner. Furthermore, we demonstrated that FBXW7α inhibits breast cancer cells survival through destabilizing GATA3, and the expression level of FBXW7α is negatively correlated with that of GATA3 in breast cancer samples. This study indicated that FBXW7α is a critical negative regulator of GATA3 and revealed a pathway for the maintenance of GATA3 abundance in breast cancer cells. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical and radiographic outcomes of bipolar hip arthroplasty with a cementless porous-coated anatomic femoral component. Methods: Fifty-nine patients (86 hips) with a minimum 3.5-year follow-up were followed up for a mean of 5.2 years (from January 2005 to January 2007). Standard clinical evaluation utilizing the Harris hip score and radiographic evaluation based on the criteria of the Hip Society were used in this prospective study. Radiographic assessment included evaluation of calcar remodeling and pedestal formation. Results: The average age of the patients (24 men and 35 women) at the time of surgery was 71.4 years (range, 69-84 years). The average preoperative Harris hip score was 48.5 ± 4.0 (range, 25-65) points, pain score 15.2 ± 3.9 (range, 0-20) points and functional score 26.7 ± 4.6 (range, 9-40) points. At the time of the latest follow-up, the average Harris hip score was 96.1 ± 2.1 (range, 67-100) points, pain score 42.6 ± 6.3 (range, 32-54) points and functional score 45.5 ± 4.7 (range, 29-56) points. Five hips (5.81%) had pain in the anterior part of the thigh. Two hips (2.33%) required revision of the femoral component because of aseptic loosening and periprosthetic fracture. Radiographic assessment revealed consistent evidence of proximal bone ingrowth. No completely radiolucent lines were identified, except around stems that had loosened. Twenty-seven femoral components (31.4%) had associated slight pedestal formation. No osteolytic lesions of the femur were identified. Nonprogressive pelvic osteolysis was identified in four hips, none of the lesions being ≥2 mm in diameter. Conclusion: An anatomically designed prosthesis can provide good clinical results, with low incidence of thigh pain and loosening of the component. [ABSTRACT FROM AUTHOR]

A low‐power consuming amplitude‐shift keying (ASK) modulator designed in 130 nm CMOS technology and operating at 10.5 GHz frequency is presented in this work. The modulator is based on current‐reuse voltage‐controlled oscillator (VCO) which uses the effects of adaptive body‐biasing and injection locking (IL) to achieve low‐phase noise and low‐power operation. The VCO has a phase noise of −106 dBc/Hz at 1 MHz offset. The ASK modulator consumes 790 μW with a 1.1 V voltage supply and draws an average current of 719 μA. For applying the bulk‐biasing signal, a deep n‐well NMOS is used in the PMOS‐NMOS oscillator pair which isolates the substrate and avoids the current path through it. The post‐layout simulation results of the 0.5 × 0.5 mm2 modulator IC verify its low‐power, low‐phase noise operation. It is intended for use in self‐powered active high data rate radio‐frequency identification (RFID) tags. [ABSTRACT FROM AUTHOR]

Aims: Intracerebral hemorrhage (ICH) is a disease with high rates of disability and mortality. The role of epidermal growth factor receptor 1 (ERBB1) in ICH was elucidated in this study. Methods: ICH model was constructed by injecting autologous arterial blood into the right basal ganglia. The protein level of ERBB1 was detected by western blot analysis. To up‐ and downregulation of ERBB1 in rats, intraventricular injection of a lentivirus overexpression vector of ERBB1 and AG1478 (a specific inhibitor of ERBB1) was used. The cell apoptosis, neuronal loss, and pro‐inflammatory cytokines were assessed by TUNEL, Nissl staining, and ELISA. Meanwhile, behavioral cognitive impairment of ICH rats was evaluated after ERBB1‐targeted interventions. Results: ERBB1 increased significantly in brain tissue of ICH rats. Overexpression of ERBB1 remarkably reduced cell apoptosis and neuronal loss induced by ICH, as well as pro‐inflammatory cytokines and oxidative stress. Meanwhile, the behavioral and cognitive impairment of ICH rats were alleviated after upregulation of ERBB1; however, the secondary brain injury (SBI) was aggravated by AG1478 treatment. Furthermore, the upregulation of PLC‐γ and PKC in ICH rats was reversed by AG1478 treatment. Conclusions: ERBB1 can improve SBI and has a neuroprotective effect in experimental ICH rats via PLC‐γ/PKC pathway. [ABSTRACT FROM AUTHOR]

A low power consumption Amplitude Shift Keying (ASK) modulator employing current reuse cross‐coupled (CRC) LC‐VCO topology and direct injection locking (IL) technique at 10.5‐GHz frequency is presented in this paper. The modulator consumes 864 μW with a DC supply of 1.2 V drawing an average current of 720 μA. The differential VCO is composed of a PMOS‐NMOS pair in stacked series cross‐coupled connection enabling current reuse which results in reduction of the average current drawn from the power source. For comparison, the ASK modulator is also realized with conventional cross‐coupled (CC) topology using NMOS pair. Both circuit approaches are carried out in GF 130‐nm CMOS technology and the post‐layout simulation results of 0.5 × 0.5 mm2 integrated circuits (ICs) show that the CRC topology consumes less power and half of the average current compared to CC topology. Owing to low power requirements, the CRC ASK modulator can be used in self‐powered active Radio Frequency Identification (RFID) tag transmitters for higher data rates. [ABSTRACT FROM AUTHOR]

Poly(vinyl pyridine) has widely been used as a pH‐responsive polymer to trigger changes in self‐assembly of block copolymer micelles. However, the polymer is known to display toxic features, which limits its ultimate applicability for biological applications. Here, poly(4‐vinyl imidazole) (P4VIm), a much more biocompatible polymer, is used as a pH‐responsive block to modulate the self‐assembly of ABC triblock terpolymers. In this article, the synthesis of the poly(1‐acryloyl fructopyranose)‐block‐ poly(n‐butyl acrylate)‐block‐ poly(4‐vinyl imidazole) (PFruA52‐b‐PBuA300‐b‐P4VIm250) triblock terpolymers is first discussed by sequential reversible addition fragmentation chain transfer (RAFT) polymerization. Subsequently, the structure formation of the triblock terpolymer is elucidated by step‐wise solvent exchange. The polymer readily dissolves in methanol, but self‐assembles into micelles with PBuA cores and mixed shell in methanol–water mixtures. Solvent exchange against buffer solutions of pH 6–6.5 leads to collapse of P4VIm due to deprotonation and induces self‐assembly into caterpillar‐like non‐spherical nanoparticles, most likely via the formation of intermediate Janus particles. The rearrangement into larger hierarchical structure, as seen by small angle X‐ray scattering (SAXS), is found to process within several hours. The article is concluded by demonstrating lower cytotoxicity values for the present polymer in comparison to a structurally analogous triblock terpolymer based on poly(vinyl pyridine). [ABSTRACT FROM AUTHOR]

Polydimethylsiloxanes (PDMS) foam as one of next-generation polymer foam materials shows poor surface adhesion and limited functionality, which greatly restricts its potential applications. Fabrication of advanced PDMS foam materials with multiple functionalities remains a critical challenge. In this study, unprecedented self-adhesive PDMS foam materials are reported with worm-like rough structure and reactive groups for fabricating multifunctional PDMS foam nanocomposites decorated with MXene/cellulose nanofiber (MXene/CNF) interconnected network by a facile silicone foaming and dip-coating strategy followed by silane surface modification. Interestingly, such self-adhesive PDMS foam produces strong interfacial adhesion with the hybrid MXene/CNF nano-coatings. Consequently, the optimized PDMS foam nanocomposites have excellent surface super-hydrophobicity (water contact angle of ≈159o), tunable electrical conductivity (from 10-8 to 10 S m-1), stable compressive cyclic reliability in both wide-temperature range (from -20 to 200 °C) and complex environments (acid, sodium, and alkali conditions), outstanding flame resistance (LOI value of >27% and low smoke production rate), good thermal insulating performance and reliable strain sensing in various stress modes and complex environmental conditions. It provides a new route for the rational design and development of advanced PDMS foam nanocomposites with versatile multifunctionalities for various promising applications such as intelligent healthcare monitoring and fire-safe thermal insulation. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A transition‐metal free three‐component coupling reaction of azaindoles, C60, and bromoalkanes/triphenylamines has been developed to provide an efficient access to diverse azaindole functionalized 1,4‐C60 adducts. This protocol exhibits low cost, operational simplicity, wide substrate scope, and mild and convenient conditions. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is a serious ischemic heart disease. Regulatory T cells (Tregs) participate in AMI. This article aims to investigate the mechanism of action of Tregs in AMI. We constructed AMI mouse model. Then, AMI mouse and mouse macrophages (RAW264.7) were treated with Tregs or Treg‐derived exosomes. The cardiac function of mice was detected. Triphenyl‐tetrazolium chloride and TdT‐mediated dUTP nick‐end labeling staining were performed to detect the myocardial infarct size or apoptosis. The proportions of macrophages were analyzed by flow cytometry. Enzyme linked immunosorbent assay and quantitative real‐time PCR was performed to estimate the levels of cytokines and genes. We found that Tregs ameliorated cardiac function, reduced myocardial infarct size and inhibited apoptosis of myocardial cells in AMI mice. Moreover, Treg‐derived exosomes reduced myocardial infarct size and repressed apoptosis of myocardial cells in AMI mice. Furthermore, Treg‐derived exosomes suppressed the expression of M1 macrophage markers, and promoted the expression of M2 macrophage markers in myocardial tissues of AMI mice and RAW264.7 cells. In conclusion, our work demonstrates that exosomes derived from Tregs ameliorate AMI by promoting macrophage M2 polarization. Thus, Tregs may be an essential cell for AMI treatment. [ABSTRACT FROM AUTHOR]

The BiS2‐based layered superconductors with structures similar to those of cuprates and iron‐based superconductors have stimulated much research interest. Here, a new quaternary compound is reported, Bi5O4S3Cl, which crystalizes in a tetragonal structure with P4/mmm (No. 123) space group having alternately stacking unique BiS3 layers and Bi2O2 layers along the c‐axis with a Cl atom located at the center of the unit cell. A superconducting transition above 3 K is observed for both electrical transport and magnetic measurements. Hall resistivity measurements show its multiband character with a conduction dominated by electron‐like charge carriers. The first‐principles calculations exhibit that the semiconducting parent phase Bi5O4S3Cl becomes metallic when sulfur vacancies are introduced, which hints the origin of superconductivity in Bi5O4S3Cl. The findings will inspire the exploration of new BiS‐based superconductors. [ABSTRACT FROM AUTHOR]

Ca2Ga2GeO7: Pr3+ (0.1%) is prepared by sintering stoichiometric amounts of CaCO3, Ga2O3, GeO2, and Pr6O11 in air (Al2O3, crucible, 1300 °C, 2 h). [ABSTRACT FROM AUTHOR]

The synthesis of a large variety of the desired heterocyclic structures becomes possible under microwaves with high regio- and chemoselectivity. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is known to disproportionately affect older individuals. How aging processes affect SARS‐CoV‐2 infection and disease progression remains largely unknown. Here, we found that DNA damage, one of the hallmarks of aging, promoted SARS‐CoV‐2 infection in vitro and in vivo. SARS‐CoV‐2 entry was facilitated by DNA damage caused by extrinsic genotoxic stress or telomere dysfunction and hampered by inhibition of the DNA damage response (DDR). Mechanistic analysis revealed that DDR increased expression of angiotensin‐converting enzyme 2 (ACE2), the primary receptor of SARS‐CoV‐2, by activation of transcription factor c‐Jun. Importantly, in vivo experiment using a mouse‐adapted viral strain also verified the significant roles of DNA damage in viral entry and severity of infection. Expression of ACE2 was elevated in the older human and mice tissues and positively correlated with γH2AX, a DNA damage biomarker, and phosphorylated c‐Jun (p‐c‐Jun). Finally, nicotinamide mononucleotide (NMN) and MDL‐800, which promote DNA repair, alleviated SARS‐CoV‐2 infection and disease severity in vitro and in vivo. Taken together, our data provide insights into the age‐associated differences in SARS‐CoV‐2 infection and a novel approach for antiviral intervention. [ABSTRACT FROM AUTHOR]

The one-pot transformation involves the formation of four new C-C and two new C-N bonds, as well as the construction of three new rings with efficient use of all reactants. [ABSTRACT FROM AUTHOR]

Currently, the cryopreservation of human spermatozoa must overcome the adverse effects of excessive oxidation. In this study, we aimed to evaluate the effect of supplementation of cryopreservation medium with cyanidin‐3‐Ο‐glucoside (C3G) on sperm quality. Semen samples were obtained from men with normozoospermia according to WHO criteria (n = 39). The sperm parameter values were compared after cryopreservation in medium supplemented with and without C3G.Compared with the control group (without additive), low doses (50 μM and 100 μM) of C3G improved sperm viability and motility and decreased the reactive oxygen species (ROS) of spermatozoa, while high doses (200 μM) of C3G did not obviously enhance sperm quality. The amount of DNA fragmentation index (DFI) and high DNA stainability (HDS) after freezing were higher in the control group than in the C3G supplementation groups. Low‐concentration C3G supplementation (50 μM) was negatively correlated with sperm ROS levels (r = −0.2, p = 0.03). Collectively, our findings suggest that C3G could be an efficient semen cryoprotectant that ameliorates oxidative stress in human sperm during cryopreservation. [ABSTRACT FROM AUTHOR]

A simple and efficient synthesis of pyrrolo[2,3,4- kl]acridine-1-one derivatives via the cascade reaction of isatins with enaminones catalyzed by silica sulfuric acid (SSA) has been established. In this reactions, SSA shows a highly catalytic nature: easy to handle procedure, short reaction time, recycle exploitation, insensitivity to air and moisture, and excellent isolated yields. The catalyst could be recycled at least five times. [ABSTRACT FROM AUTHOR]

Although Alzheimer's disease (AD) is associated with an increased risk of intracerebral hemorrhage (ICH) caused by hypertension and cerebral amyloid angiopathy, the precise clinical course after hypertensive ICH in AD patients is still unknown. In this study, we investigated how striatal ICH, a frequent site for hypertensive ICH, affected the prognosis of AD. We employed 17‐ and 18‐month‐old male 5XFAD (5X) mice and littermate (LT) controls, and striatal ICH was induced by collagenase injection. First, to address the acute effects of ICH on 5X mice, hemorrhagic volume and brain edema were evaluated 3 days after ICH. Next, to address the long‐term effects of ICH on 5X mice, morbidity, mortality, neurological function (beam‐walking and rotarod tests), and cognitive function (Y‐maze and nest‐building tests) were monitored. Twenty‐eight days later, the animals were euthanized, their brains were isolated, and the cytotoxic alterations were investigated. The results revealed that the acute effects of ICH were not significantly different between 5X and LT mice. In contrast, 5X mice showed significantly higher morbidity and mortality in response to ICH, as well as delayed neurological function recovery, compared to LT mice through 28 days. ICH did not affect cognitive function in either group. Infiltrated macrophages in the perihemorrhagic cortex, gp91phox, p67phox, and COX‐2 were significantly increased in 5X mice in response to ICH. We demonstrated that striatal ICH deteriorated prognosis and delayed neurofunctional recovery in 5X mice, which might be associated with enhanced oxidative stress in the presence of AD‐like pathology. [ABSTRACT FROM AUTHOR]

In this article, a broadband beam scanning antenna array is proposed in Q‐band attributed to miniaturized size, wideband and high integration. A patch antenna element is utilized with a back cavity, which is formed by metallic via holes and ground plane. A 1 × 4 series fed sub‐array is implemented by the patch element using multilayer PCB. Four symmetrical sub‐arrays and Butler matrix feeding network are used to form the antenna array with high gain and decrease side lobes. The Butler matrix is implemented by substrate integrated coaxial line, which provides low loss of around 0.09 dB/mm from 40 to 50 GHz. The measured antenna array bandwidth is 9.8 GHz (21.8%) under the condition of voltage standing wave ratio less than 2. The main beam of the antenna array in azimuth direction is tilted to −28.5°, −14.1°, 18.4° and 35.6° and the gains are 13.11, 13.88, 14.02 and 11.78 dBi at 45 GHz, respectively. Both the measured and simulated results agree well. [ABSTRACT FROM AUTHOR]

Abstract: An iron‐catalyzed cyanoalkylation using azobisisobutyronitrile (AIBN) is reported. With unactivated double bond as the radical acceptor, N‐allyl anilines underwent cyanoisopropylation/cyclization cascade to afford 3‐cyanoalkyl indolines bearing a tertiary nitrile moiety, which were otherwise unavailable. Excellent exo‐selectivity was always observed, and such a selectivity and the unusual performance of the iron catalyst might be related to the metal bridging between the radical and the substrate. [ABSTRACT FROM AUTHOR]

Background Tumor necrosis factor receptor-associated factor 1 ( TRAF1) is a member of the TRAF family and is dysregulated in diseases, such as atheroma, lymphoma, and solid tumors, but the role of TRAF1 in gastric cancer remains unknown. This study was aimed to investigate the role of TRAF1 in Helicobacter pylori ( H. pylori)-related cell apoptosis and gastric carcinogenesis. Materials and methods The mRNA and protein expression levels of TRAF1 were measured in a panel of gastric cancer cell lines and in H. pylori -infected mice by quantitative real-time PCR ( qPCR) and Western blotting. The transcription factor that mainly affects transcription of TRAF1 during H. pylori infection was identified. The roles of H. pylori virulence factors that regulate TRAF1 expression were analyzed using isogenic cagA-, vacA-, and cagE-null mutants. The effects of TRAF1 on gastric cell viability and apoptosis during H. pylori infection were detected using the standard MTS (cell viability) assay and flow cytometry, respectively. Results H. pylori infection induced TRAF1 overexpression in both gastric epithelial cells and mice. The expression of TRAF1 in response to H. pylori infection was majorly regulated by the activation of NF-κB and was strongly related to H. pylori virulence factor CagA. The upregulation of TRAF1 inhibited cell apoptosis and increased the viability of infected cells. Conclusions H. pylori infection induces the overexpression of TRAF1 in gastric epithelial cells. The upregulation of TRAF1 plays an antiapoptotic role in H. pylori -infected gastric cells and may contribute to the gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

With a given free-flow electrophoresis device, reasonable conditions (electric field strength, carrier buffer conductivity, and flow rate) are crucial for an optimized separation. However, there has been no experimental study on how to choose reasonable general conditions for a free-flow electrophoresis device with a thermoelectric cooler in view of Joule heat generation. Herein, comparative experiments were carried out to propose the selection procedure of general conditions in this study. The experimental results demonstrated that appropriate conditions were (i) <67 V/cm electric field strength; (ii) lower than 1.3 mS/cm carrier buffer conductivity (Tris-HCl: 20 mM Tris was titrated by HCl to pH 8.0); and (iii) higher than 3.6 mL/min carrier buffer flow rate. Furthermore, under inappropriate conditions (e.g. 400 V voltage and 40 mM Tris-HCl carrier buffer), the free-flow electrophoresis separation would be destroyed by bubbles caused by more Joule heating. Additionally, a series of applications under the appropriate conditions were performed with samples of model dyes, proteins (bovine serum albumin, myoglobin, and cytochrome c), and cells ( Escherichia coli, Streptococcus thermophilus, and Saccharomyces cerevisiae). The separation results showed that under the appropriate conditions, separation efficiency was obviously better than that in the previous experiments with randomly or empirically selected conditions. [ABSTRACT FROM AUTHOR]

The title compounds (III) and (V) are efficiently obtained by cascade reaction of isatins with enaminones. [ABSTRACT FROM AUTHOR]

Uneven flow in free-flow electrophoresis (FFE) with a gravity-induced fraction collector caused by air bubbles in outlets and/or imbalance of the surface tension of collecting tubes would result in a poor separation. To solve these issues, this work describes a novel collector for FFE. The collector is composed of a self-balance unit, multisoft pipe flow controller, fraction collector, and vacuum pump. A negative pressure induced continuous air flow rapidly flowed through the self-balance unit, taking the background electrolyte and samples into the fraction collector. The developed collector has the following advantages: (i) supplying a stable and harmonious hydrodynamic environment in the separation chamber for FFE separation, (ii) effectively preventing background electrolyte and sample flow-back at the outlet of the chamber and improving the resolution, (iii) increasing the preparative scale of the separation, and (iv) simplifying the operation. In addition, the cost of the FFE device was reduced without using a multichannel peristaltic pump for sample collection. Finally, comparative FFE experiments on dyes, proteins, and cells were carried out. It is evident that the new developed collector could overcome the problems inherent in the previous gravity-induced self-balance collector. [ABSTRACT FROM AUTHOR]

In China, some forensic cases are caused by barbiturates. Thus, the determination of trace level barbiturates in body fluid is important for the poisoning investigation. In this study, an online large-volume sample stacking (LVSS) with polarity switching in capillary electrophoresis (CE) was applied for the sensitive determination of barbiturates. This technique involves injecting a large volume of sample into a capillary and removing the sample matrix plug out of the capillary by reversing the polarity. Quantitation limit obtained was 0.048, 0.057, 0.039, and 0.015 μg/mL for secobarbital, amobarbital, barbital, and phenobarbital (signal-to-noise ratio = 9). By using LVSS, the stacking was simply achieved at 171.7-, 169.7-, 202.7-, and 169.1-fold for the above four barbiturates. The relative standard deviation values of intraday and interday were <2.11% and 4.69%, respectively. Recoveries were ranged from 83.7 to 105.2%. Finally, the trace analysis method was applied to the analysis of real forensic specimens and has achieved satisfactory results. [ABSTRACT FROM AUTHOR]

isolation, structure elucidation, plausible biogenetic pathway and biological activities [ABSTRACT FROM AUTHOR]

isolation, structure elucidation, plausible biogenetic pathway and biological activities [ABSTRACT FROM AUTHOR]

The title compounds are obtained with high regio- and stereoselectivity by three-component domino reaction of glutaraldehyde, malononitrile, and β-ketoamides under microwave irradiation. [ABSTRACT FROM AUTHOR]

The outcome of the reaction is strongly temperature-dependent. [ABSTRACT FROM AUTHOR]

Reductive cyclization of nitroaryl substrates using a low valent titanium reagent allows the synthesis of the title compounds (II) and (IV). [ABSTRACT FROM AUTHOR]