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Integral imaging (InIm) 3D displays provide realistic 3D images with comfortable viewing experiences. However, existing approaches struggle to achieve high spatial resolution reproduction without relying on temporal or spatial multiplexing methods, which increases system complexity. Although precise control approaches for voxel formation have been explored to address this challenge, the existing methods lack systematic analysis theories for identifying the key factors affecting spatial resolution. In this study, a novel analysis framework is proposed that uses a point spread function (PSF) to characterize voxel formation. An analytical model based on the obtained PSF is established to achieve an aliasing‐free display. This framework identifies optimization directions for improving the spatial resolution, specifically by reducing the Gaussian blur caused by wavefront aberration in the lens unit. A targeted optimization of a compound lens array is conducted to achieve precise control of voxel formation. In these experiments, an InIm 3D display system prototype that substantially outperforms conventional InIm 3D displays is developed. The prototype achieves a 74.6% reduction in the system PSF and a 29.85% reduction in voxel size, enabling aliasing‐free voxels and a 2.82 times higher resolution in the InIm 3D display. [ABSTRACT FROM AUTHOR]

Neratinib (an active pharmaceutical ingredient [API]) is an irreversible pan‐human epidermal growth factor receptor (HER) inhibitor used to treat HER2‐positive breast cancer. The dosage form (marketed in the United States, China, Europe, and other regions) is a tablet for oral administration, and the brand product (NERLYNX) has patent protection for the crystalline neratinib maleate monohydrate form. This paper describes the product development using stable crystalline neratinib maleate anhydrous form, stability study, bioequivalence (BE) study of the products, and discussion of the adverse effects observed in the clinical study. [ABSTRACT FROM AUTHOR]

Previous evidence on heatwaves' impact on mental health outpatient visits is limited, especially uncertainty on how different heatwave definitions affect this relationship. In this time‐series study, we assessed the association between heatwaves and outpatient visits for mental disorders in Guangzhou, China. Daily outpatient visits for mental disorders and its specific categories (schizophrenia, mood, and neurotic disorders) were sourced from the Urban Resident‐based Basic Medical Insurance (URBMI) and the Urban Employee‐based Basic Medical Insurance (UEBMI) claims databases in Guangzhou from 2010 to 2014. The study employed nine heatwave definitions, based on combinations of three daily mean temperature thresholds (90th, 92.5th, and 95th percentiles) and durations (2, 3, and 4 days). Using quasi‐Poisson generalized linear models (GLMs), we estimated the risks (at lag 0 day) and cumulative effects (lag 0–10 days) of heatwaves on mental disorder outpatient visits. Age, gender, types of medical insurance were considered as potential effect modifiers. We observed a positive association between heatwaves and increased total outpatient visits for mental disorders, both at lag 0 day and during lag 0–10 days. The impact of heatwave was significant at lag 0 day for schizophrenia, mood and neurotic disorders visits, it remained significant for neurotic and mood disorders visits during lag 0–10 days. Heatwave durations lasting more than 4 days were associated with higher relative risks of mental disorders at lag 0 day. Older adults had relatively higher effect estimations than younger individuals. This research highlights the effects of extreme heat on mental health. Plain Language Summary: The rising frequency, duration, and intensity of heatwaves underscore the critical need to understand their effects on mental health disorders. This study fills a significant gap in research by examining the relationship between different definitions of heatwaves and outpatient visits for mental disorders, considering variations across medical insurance types, age, and gender. These findings are helpful for developing targeted preventive measures and healthcare strategies to protect vulnerable populations. Key Points: Exposure to extreme heat is associated with an increase in outpatient visits for overall mental disordersExposure to extreme heat is linked to a rise in visits for schizophrenia, mood disorders, and neurotic disordersThe effects of heatwaves on outpatient visits for mental disorders vary depending on the definitions of heatwaves used [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by complex pathogenesis mechanisms. Among these, β‐amyloid plaques and hyperphosphorylated Tau protein tangles have been identified as significant contributors to neuronal damage. This study investigates thonningianin A (TA) from Penthorum chinense Pursh (PCP) as a potential inhibitor targeting these pivotal proteins in AD progression. The inhibitory potential of PCP and TA on Aβ fibrillization was initially investigated. Subsequently, ultra‐high performance liquid chromatography‐quadrupole time‐of‐flight tandem mass spectrometry and biolayer interferometry were employed to determine TA's affinity for both Aβ and Tau. The inhibitory effects of TA on the levels and cytotoxicity of AD‐related proteins were then assessed. In 3xTg‐AD mice, the therapeutic potential of TA was evaluated. Additionally, the molecular interactions between TA and either Aβ or Tau were explored using molecular docking. We found that PCP‐total ethanol extract and TA significantly inhibited Aβ fibrillization. Additionally, TA demonstrated strong affinity to Aβ and Tau, reduced levels of amyloid precursor protein and Tau, and alleviated mitochondrial distress in PC‐12 cells. In 3xTg‐AD mice, TA improved cognition, reduced Aβ and Tau pathology, and strengthened neurons. Moreover, molecular analyses revealed efficient binding of TA to Aβ and Tau. In conclusion, TA, derived from PCP, shows significant neuroprotection against AD proteins, highlighting its potential as an anti‐AD drug candidate. [ABSTRACT FROM AUTHOR]

This study examines the influence of corporate site visits on information acquisition and dissemination by independent directors (IDs). Employing two unique sources of data from Chinese listed firms based on the mandatory disclosure of IDs' (i) site visit activities and (ii) opinions about corporate decisions, we find that the acquisition of firm‐specific information and the dissemination of such information to the market are greater among IDs who conduct visits than their counterparts without such visits. Moreover, this effect is more pronounced in firms with complex information environments, in firms with lower proprietary costs, and among IDs with greater internal information asymmetry, superior external information, and stronger incentives and abilities to perform their duties. Furthermore, the firm‐specific information disseminated by IDs leads to stronger market reactions and improves stock price efficiency. Our study shows that site visits contribute to the informational role of IDs, and our evidence offers important corporate governance and regulatory implications. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effects and molecular mechanisms of tetrahedral framework nucleic acids‐microRNA22 (tFNAs‐miR22) on inhibiting pathological retinal neovascularization (RNV) and restoring physiological retinal vessels. A novel DNA nanocomplex (tFNAs‐miR22) was synthesised by modifying microRNA‐22 (miR22) through attachment onto tetrahedral frame nucleic acids (tFNAs), which possess diverse biological functions. Cell proliferation, wound healing, and tube formation were employed for in vitro assays to investigate the angiogenic function of cells. Oxygen‐induced retinopathy (OIR) model was utilised to examine the effects of reducing pathological neovascularization (RNV) and inhibiting vascular occlusion in vivo. In vitro, tFNAs‐miR22 demonstrated the ability to penetrate endothelial cells and effectively suppress cell proliferation, tube formation, and migration in a hypoxic environment. In vivo, tFNAs‐miR22 exhibited promising results in reducing RNV and promoting the restoration of normal retinal blood vessels in OIR model through modulation of the Wnt pathway. This study provided a theoretical basis for the further understanding of RNV, and highlighted the innovative and potential of tFNAs‐miR22 as a therapeutic option for ischemic retinal diseases. [ABSTRACT FROM AUTHOR]

Xixin–Ganjiang herb pair (XGHP) is a classic combination for warming the lungs to dissolve phlegm and is often used to treat a variety of chronic lung diseases; it can treat the syndrome of cold phlegm obstruction of lungs. First, ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) was used to examine the composition of XGHP, and network pharmacology was used to predict its potential core targets and signaling pathways in the current study. Second, a rat model of chronic obstructive pulmonary disease (COPD) was established for assessing the anti‐COPD activity of XGHP, and metabolomics was used to explore the biomarkers and metabolic pathways. Finally, the sample was validated using molecular docking and Western blotting. The integration of metabolomics and network pharmacology results identified 11 targets, 3 biomarkers, 3 pathways, and 2 metabolic pathways. Western blotting showed that XGHP effectively regulated the expression of core proteins via multiple signaling pathways (downregulation of toll‐like receptor 4 [TLR4] and upregulation of serine/threonine‐protein kinase 1 [p‐AKT1] and nitric oxide synthase 3 [NOS3]). Molecular docking results showed that the 10 potentially active components of XGHP have good affinity with tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), matrix metalloproteinase 9 (MMP‐9), TLR4, p‐AKT1, and NOS3. Our findings suggest that XGHP may regulate glucolipid metabolism, improve energy supply, and inhibit inflammatory responses (TNF‐α, IL‐6, and MMP‐9) via the PI3K‐Akt signaling pathway and HIF‐1 signaling pathway in the management of COPD. [ABSTRACT FROM AUTHOR]

Light shaping diffuser (LSD) is a crucial component in integral imaging based light field display for achieving continuous 3D images. However, LSD also constrains the display resolution in wide viewing angles. To addressing this issue, this study conducts thorough analyses. The light homogenization characteristics of LSD are proposed, complementing the understanding of LSD's mechanism for achieving continuous 3D images. Furthermore, the scattering function of LSD is established for the first time, explaining the mechanism behind LSD constraining resolution in wide viewing angles. The proposed scattering function can guide the optimization design of resolution enhanced integral imaging based light field display. [ABSTRACT FROM AUTHOR]

In this article, a modified scheme of the fast dipole method (FDM) is proposed based on the Cartesian tensor. To achieve separation between the field and the source, the Taylor series used in the FDM is an incomplete second‐order expansion, which limits computational accuracy and flexibility. To address this issue, a Cartesian tensor is employed to expand the interactions between the far‐group pairs. This approach allows for a complete expansion of any order and offers flexibility in precision control, enabling a balance between computational efficiency and accuracy requirements across different application scenarios. Moreover, the computational accuracy of the proposed method can be improved without a substantial increase in time and memory requirements compared to the FDM. The validity and accuracy of the proposed method are demonstrated with numerical examples. [ABSTRACT FROM AUTHOR]

This article discusses a case of hydroxychloroquine-induced acute generalized exanthematous pustulosis (AGEP) that was successfully treated with secukinumab, an IL-17 antagonist. AGEP is a rare severe cutaneous adverse reaction characterized by the acute onset of widespread pustules on an erythematous base. Hydroxychloroquine is a commonly used antimalarial drug that can cause AGEP as a skin adverse reaction. The patient in this case experienced worsening symptoms despite treatment with systemic corticosteroids and cyclosporine, but showed significant improvement after receiving secukinumab. This case suggests that IL-17 antagonists could be a promising therapeutic option for refractory cases of AGEP. [Extracted from the article]

Background: Malnutrition is highly prevalent and associated with complications and mortality in patients with cirrhosis. Methods: This was a prospective observational study. Patients with cirrhosis were screened using the Nutritional Risk Screening 2002, the Royal Free Hospital‐Nutritional Prioritizing Tool and the Skeletal Muscle Index. Then, the sensitivity, specificity, positive and negative predictive values, and consistency with the Global Leadership Initiative on Malnutrition criteria results were calculated. We also analysed the association between nutritional status and short‐term prognosis. Results: We enrolled 125 patients with cirrhosis, of whom 59.20% and 60.00% were malnourished based on the Global Leadership Initiative on Malnutrition criteria and Skeletal Muscle Index. Some 53.60% and 65.60%, respectively, were classified medium‐to‐high nutritional risk by Nutritional Risk Screening 2002 and the Royal Free Hospital‐Nutritional Prioritizing Tool. The Royal Free Hospital‐Nutritional Prioritizing Tool had the best predictive value, and it was more sensitive and had a better negative predictive value than the Nutritional Risk Screening 2002 Tool. The Skeletal Muscle Index also had good sensitivity and predictive value. The Royal Free Hospital‐Nutritional Prioritizing Tool, Skeletal Muscle Index and Global Leadership Initiative on Malnutrition criteria showed high concordance. The 3‐ and 6‐month mortality rates were significantly higher for patients with moderate‐to‐high nutritional risk or malnutrition, regardless of the tool. Conclusions: When assessing cirrhosis with the Global Leadership Initiative on Malnutrition criteria, the Royal Free Hospital‐Nutritional Prioritizing Tool is best for nutritional screening and the Skeletal Muscle Index is also a good nutritional assessment tool. Key points: Diagnosis and treatment of liver diseases were considered.The Royal Free Hospital‐Nutritional Prioritizing Tool score is not affected by the presence of oedema and ascites and is therefore more advantageous than the Nutritional Risk Screening 2002, which is more commonly used in clinical practice in cirrhotic patients.The results of the present study show that the Royal Free Hospital‐Nutritional Prioritizing Tool is more valuable than the Nutritional Risk Screening 2002 for determining the short‐term prognosis of patients with liver cirrhosis.The study found good concordance between the Skeletal Muscle Index (SMI) and Global Leadership Initiative on Malnutrition criteria in patients with cirrhosis. Therefore, lumbar 3‐SMI can be used to assess the nutritional status of these patients.C‐reactive protein, interleukin‐6 and procalcitonin levels significantly increased in patients with moderate‐to‐high nutritional risk or malnutrition compared to their counterparts. [ABSTRACT FROM AUTHOR]

In recent years, SnO2 quantum dots (QDs) have been widely used for preparing the electron‐transport layer within perovskite solar cells (PSCs). However, the fabricated devices exhibit an evident hysteresis unless interlayer materials are introduced to passivate or prevent the formation of trap states at the SnO2–perovskite interface. Herein, the use of the zwitterion 3‐(1‐pyridinio)‐1‐propanesulfonate (PPS) as additive inside the SnO2 QDs solution is proposed. The results highlight that the PPS plays a multifunctional role by accelerating the synthesis of the QDs, enhancing the electron transfer and passivating defects at the SnO2–perovskite interface. The resulting PSCs with SnO2 QDs incorporating PPS exhibit a remarkable reduction in hysteresis index (HI) compared to those prepared with thiourea or without any additives. This reduction in HI suggests that PPS serves as a cost‐effective alternative additive for SnO2 QDs preparation, eliminating the need for additional interlayers or expensive additives. [ABSTRACT FROM AUTHOR]

Summary: Nuclear‐cytoplasmic trafficking is crucial for protein synthesis in eukaryotic cells due to the spatial separation of transcription and translation by the nuclear envelope. However, the mechanism underlying this process remains largely unknown in plants.In this study, we isolated a maize (Zea mays) mutant designated developmentally delayed kernel 1 (ddk1), which exhibits delayed seed development and slower filling. Ddk1 encodes a plant‐specific protein known as Importin‐4 β, and its mutation results in reduced 80S monosomes and suppressed protein synthesis.Through our investigations, we found that DDK1 interacts with eIF1A proteins in vivo. However, in vitro experiments revealed that this interaction exhibits low affinity in the absence of RanGTP. Additionally, while the eIF1A protein primarily localizes to the cytoplasm in the wild‐type, it remains significantly retained within the nuclei of ddk1 mutants. These observations suggest that DDK1 functions as an exportin and collaborates with RanGTP to facilitate the nuclear export of eIF1A, consequently regulating endosperm development at the translational level.Importantly, both DDK1 and eIF1A are conserved among various plant species, implying the preservation of this regulatory module across diverse plants. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is a leading cause of cancer‐related deaths in men worldwide. Despite advances in treatment strategies, there is still a need for novel therapeutic targets and approaches. Ferroptosis has emerged as a critical process in the development and progression of several cancers, including prostate cancer (PCA). In this study, we investigate the role of MT1G, a gene implicated in immune responses and ferroptosis, in the pathogenesis of PCA. Our objective is to elucidate its prognostic significance and its impact on the tumor microenvironment, while exploring its potential in enhancing the sensitivity to immune checkpoint inhibitor (ICI) therapy. Methods: We utilized a combination of in silico analysis and experimental techniques to investigate the role of MT1G in PCA. First, we analyzed large‐scale genomic datasets to assess the expression pattern and prognostic significance of MT1G in PCA patients. Subsequently, we performed functional assays to explore the impact of MT1G in PCA and its potential involvement in modulating immune responses. In addition, we conducted in vivo experiments to evaluate the effect of MT1G on tumor growth and response to ICI therapy. Results: Our analysis revealed that MT1G expression is significantly downregulated in PCA tissues compared to normal prostate tissues and is associated with poor prognosis. Furthermore, MT1G overexpression inhibited the growth of PCA cells in vitro and in vivo. Importantly, we found that MT1G regulates the tumor microenvironment by modulating immune cell infiltration and inhibiting immunosuppressive factors. Furthermore, our study reveals a significant correlation between MT1G expression levels and the response to immune checkpoint inhibitor (ICI) therapy in prostate cancer (PCA) patients, as MT1G upregulation leads to an increase in PDL‐1 expression. These findings underscore the potential of MT1G as a promising predictive biomarker for ICI therapy response in PCA patients. Conclusion: Our study elucidates the pivotal role played by MT1G in the pathogenesis of prostate cancer (PCA) and its profound implications for prognosis. Moreover, it raises the intriguing possibility that MT1G could pave the way for novel therapeutic approaches in PCA treatment. This potential arises from its ability to orchestrate immune infiltration within the tumor microenvironment, consequently enhancing sensitivity to immune checkpoint inhibitor (ICI) therapy. Therefore, our findings hold substantial promise for advancing our comprehension of PCA and exploring innovative therapeutic strategies. [ABSTRACT FROM AUTHOR]

It is widely recognized that platinum‐based chemotherapy, particularly cisplatin therapy, can cause ototoxicity. At present, there are no Food and Drug Administration‐approved drugs to prevent or alleviate ototoxicity. Ototoxicity is generally believed to be caused by excessive reactive oxygen species production in the inner ear. Accordingly, a variety of antioxidants have been developed to protect against ototoxicity. To improve the efficiency of drug delivery to the cochlea, here, we synthesized simple and easy‐to‐obtain glutathione carbon dots (GSH CDs) with ultra‐small dimensions. The experimental results revealed that the GSH CDs have strong free‐radical scavenging activity and can restore mitochondrial function, maintain hair cell stability, and protect hair cells from cisplatin‐induced oxidative stress. Thus, GSH CDs may serve as a new therapeutic agent for preventing cisplatin‐induced ototoxicity. [ABSTRACT FROM AUTHOR]

Technostress is an undesired consequence of information and communication technology (ICT) use and might negatively affect teachers. However, there is a lack of empirical research exploring the influences of technostress creators on teachers' ICT use. This study aims to bridge this gap by exploring the structural relationship among five technostress creators (ie, techno‐complexity, techno‐overload, techno‐invasion, techno‐insecurity, and techno‐uncertainty), teachers' attitudes toward ICT, and their ICT adoption intentions. The research model was developed based on existing literature and tested using structural equation modelling. Data were collected from 289 teachers from six public elementary and secondary schools in China. The results indicate that: (a) teachers' attitude toward ICT has a significant positive effect on their ICT adoption intentions; (b) techno‐insecurity and techno‐complexity have significant negative effects on teachers' attitude toward ICT and ICT adoption intentions, respectively; (c) techno‐invasion and techno‐overload have significant positive effects on teachers' attitude toward ICT and their ICT adoption intentions, respectively; (d) techno‐uncertainty has a significant positive effect on both teachers' attitude toward ICT and their ICT adoption intentions; (e) compared to younger teachers, the attitude of teachers aged 45 and above toward ICT are more negatively affected by techno‐insecurity. Implications for the management of technostress creators are discussed. Practitioner notesWhat is already known about this topic Technostress negatively influences teachers' acceptance and adoption intention of ICT.The influences of specific technostress creators may differ.There is a lack of empirical research exploring the exact influences of technostress creators on teachers' ICT use.What the paper adds Techno‐insecurity and techno‐complexity negatively affect teachers' attitudes toward ICT and ICT adoption intentions, respectively.Techno‐invasion and techno‐overload positively affect teachers' attitudes toward ICT and their ICT adoption intentions, respectively.Techno‐uncertainty significantly positively affects teachers' attitudes toward ICT and ICT adoption intentions.The attitude of teachers aged 45 and above toward ICT is more negatively affected by techno‐insecurity.Implications for practice and/or policy Schools should provide adequate end‐user training, a friendly technical help desk, and teacher‐oriented psychological counselling programs concerning technostress to mitigate teachers' techno‐complexity and techno‐insecurity.School administrators should take measures, such as providing timely upgrades and continuous maintenance services, to ensure the reliability and accessibility of technologies.It is necessary for school ICT support staff to guide teachers, especially teachers aged 45 and above, to take positive coping strategies, such as venting, seeking social support and engaging in technical training, to deal with techno‐insecurity. [ABSTRACT FROM AUTHOR]

Tunable liquid lenses with controllable focal length attract much attention from many researchers due to the unique advantages of strong adjustability, low power consumption, fast response time, and easy integration. In the last two decades, tunable liquid lenses have already been applied in machine vision, code scanner cameras, cellphone cameras, webcams, microscopes, mini projectors, AR/VR displays, 3D displays, and so on. There is no doubt that the tunable liquid lenses play an increasingly more important role in the field of optical technology. In this review, the research background and significance of the tunable liquid lenses are introduced. Tunable liquid lenses are systematically qualified according to the driving mechanism, and their current status and latest progress are presented in detail. The existing problems, directions for future research, and current and potential applications of the tunable liquid lenses are also discussed. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relation between the expression of PD‐1, PD‐L1, CD3, CD8, Foxp3 and clinicopathological features in patients with oral leukoplakia (OLK) and oral squamous cell carcinomas (OSCC) as well as the malignant outcome in OLK patients, and to study the effect of PD‐1 and PD‐L1 on immune microenvironment in the progression of oral carcinogenesis. Methods: We evaluated the expression of PD‐1/PD‐L1 and composition of CD3+, CD8+and Foxp3+ T lymphocytes in OLK and OSCC samples by immunohistochemical (IHC) staining and analyzed their relation with clinical information and malignant transformation in OLK patients. Results: IHC staining demonstrated that the expression of PD‐1 was significantly increased in the high‐grade OLK group than in the low‐grade OLK group, while PD‐L1 was detected mainly in OSCC. The expression of CD3, CD8, and Foxp3 was found higher in the high‐grade OLK group than in the low‐grade OLK group, and the Foxp3+ cells were found more in the OSCC group than in the high‐grade OLK group. PD‐1 was significantly correlated with CD3 (p < 0.05, R = 0.52), CD8 (p < 0.05, R = 0.46), and Foxp3 (p < 0.05, R = 0.46), and the low PD‐1‐expression group showed a better malignant‐free survival than high PD‐1 expression group in the OLK (p < 0.05). Conclusion: The PD‐1/PD‐L1 may induce immune suppression in OLK and accelerate the progress of malignant transformation. [ABSTRACT FROM AUTHOR]

Background Introduction: In recent years, there has been an increase in the number of patients diagnosed with pediatric diseases who have severe Mycoplasma pneumoniae (MP) pneumonia, and there has also been an increased attention to serious extrapulmonary complications. However, cases with abdominal pain, acute abdomen, scrotal swelling and pain, and fever as the primary symptoms have been rarely reported. Case Description: A 3‐years‐and‐8‐months‐old male patient diagnosed with pediatric disease was reported with abdominal pain, scrotal swelling and pain, and fever as the primary symptoms in the present study. No respiratory symptoms were observed throughout the disease. Through computed tomography (CT) scanning, the patient was diagnosed with severe MP pneumonia based on the symptoms of abdominal pain and fever, as well as pulmonary infection, pleural effusion, and retroperitoneal exudation. Laboratory tests supported the diagnosis of MP infection, and the diagnosis was confirmed by severe MP pneumonia. The therapeutic effects of azithromycin were poor, and the symptoms were quickly alleviated with the addition of gamma globulin and methylprednisolone. After discharge, azithromycin sequential therapy was administered. The chest CT was normal at the follow‐up 1‐month later. Conclusion: Severe MP pneumonia in patients with pediatric diseases may include abdominal pain, scrotal swelling and pain, and fever as the primary symptoms. Care should be taken to avoid missed diagnoses and misdiagnoses in clinical practice. [ABSTRACT FROM AUTHOR]

The article "Negative Expression of CD117 Predicted Inferior OS and PFS in Acute Promyelocytic Leukemia" published in the International Journal of Laboratory Hematology discusses a study on the prognostic significance of CD117 in acute promyelocytic leukemia (APL). The researchers found that CD117 was an independent adverse prognostic factor for overall survival (OS) and progression-free survival (PFS) in patients with APL. The study raises concerns about the statistical methods used and suggests improvements for future research in this area. [Extracted from the article]

Background: SHR‐1707 is a humanized monoclonal antibody against amyloid‐β (Aβ). Pharmacodynamic studies in vitro showed that SHR‐1707 is more potent than lecanemab. SHR‐1707 had similar affinity to Aβ fibrils and protofibrils and relatively higher affinity to Aβ monomers than lecanemab. In 5xFAD transgenic mouse model of Alzheimer's disease (AD), SHR‐1707 safely reduced brain Aβ deposition and ameliorated memory deficits. Phase 1 studies in China (NCT04973189) and Australia (NCT04745104) had demonstrated the safety and tolerability of SHR‐1707 in healthy young adults and elderly subjects at up to 60 mg/kg. The preclinical and clinical evidence support further development of SHR‐1707. Hence, we designed a phase 1b trial of SHR‐1707 to evaluate the safety, effective dosage, and effects on brain Aβ deposition in patients with mild cognitive impairment (MCI) due to AD or mild AD. Method: This is a randomized, double‐blind, dose‐escalation, placebo‐controlled phase 1b study (NCT05681819; Figure 1). Patients with MCI due to AD or mild AD aged 55‐85 years will be randomized to placebo or intravenous SHR‐1707 at escalated doses of 5, 10, 20, and 40 mg/kg every 2 weeks for 26 weeks. Randomization will be based on the treatment to placebo ratio of 3:2 for 5 mg/kg dose group (N = 5, ≥3 ApoE ε4 carriers) and 10:2 for the remaining dose groups (for each group: N = 12, ≥5 ApoE ε4 carriers). In the following open‐label extension study, all patients will be assigned to SHR‐1707 for 52 weeks. The primary objective is to assess the safety and tolerability of 26‐week treatment of SHR‐1707. Secondary objectives are to assess effects on brain Aβ deposition by positron‐emission tomography, pharmacokinetic and pharmacodynamic profiles in blood and cerebrospinal fluid, immunogenicity, and clinical efficacy with 26‐week treatment of SHR‐1707; and long‐term safety, tolerability, and effects on brain Aβ deposition with 78‐week treatment. Figure 2 lists all study endpoints. Result: The study is ongoing in China. Topline results are expected in Q1 2024. Conclusion: This trial will obtain safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and clinical efficacy data of SHR‐1707 to support advancement to confirmatory phase 2 or 3 studies in patients with MCI due to AD and mild AD. [ABSTRACT FROM AUTHOR]

Objective: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease that leads to severe disability. A large proportion of NMOSD patients are seropositive for aquaporin‐4 autoantibodies (AQP4‐IgG, named as NMO‐IgG) targeting AQP4, which is selectively expressed on astrocytes in the central nervous system. This study tests the hypothesis that in response to NMO‐IgG, the pathogenic astrocyte‐derived exosomes are released and injure the neighboring cells. Methods: IgG purified from serum of either NMOSD patients or healthy controls was used to generate astrocyte‐derived exosomes (AST‐ExosNMO vs AST‐ExosCON) in cultured rat astrocytes. The exosomes were respectively delivered to cultured rat oligodendrocytes in vitro, tissue culture of rat optic nerve ex vivo, and rat optic nerve in vivo to evaluate the pathogenic roles of AST‐ExosNMO. The microRNA (miRNA) sequencing of AST‐Exos and verification were performed to identify the key pathogenic miRNA. The custom‐designed adeno‐associated virus (AAV) antagonizing the key miRNA was evaluated for its therapeutic effects in vivo. Moreover, the serum levels of the key exosomal miRNA were measured between NMOSD patients and healthy controls. Results: AST‐ExosNMO led to notable demyelination in both cultured oligodendrocytes and optic nerve tissue. Exosomal miR‐129‐2‐3p was identified as the key miRNA mediating the demyelinating pathogenesis via downstream target gene SMAD3. AAV antagonizing miR‐129‐2‐3p protected against demyelination in an NMOSD rodent model. The serum exosomal miR‐129‐2‐3p level was significantly elevated in NMOSD patients and correlated with disease severity. Interpretation: Astrocytes targeted by NMO‐IgG release pathogenic exosomes that could potentially be used as therapeutic targets or disease monitoring biomarkers in NMOSD. ANN NEUROL 2023;94:163–181 [ABSTRACT FROM AUTHOR]

This study aimed to explore the effect and the molecular mechanism of tetrahedral framework nucleic acids (tFNAs), a novel self‐assembled nanomaterial with excellent biocompatibility and superior endocytosis ability, in inhibition of pathological retinal neovascularization (RNV) and more importantly, in amelioration of vaso‐obliteration (VO) in ischaemic retinopathy. tFNAs were synthesized from four single‐stranded DNAs (ssDNAs). Cell proliferation, wound healing and tube formation assays were performed to explore cellular angiogenic functions in vitro. The effects of tFNAs on reducing angiogenesis and inhibiting VO were explored by oxygen‐induced retinopathy (OIR) model in vivo. In vitro, tFNAs were capable to enter endothelial cells (ECs), inhibit cell proliferation, tube formation and migration under hypoxic conditions. In vivo, tFNAs successfully reduce RNV and inhibit VO in OIR model via the PI3K/AKT/mTOR/S6K pathway, while vascular endothelial growth factor fusion protein, Aflibercept, could reduce RNV but not inhibit VO. This study provides a theoretical basis for the further understanding of RNV and suggests that tFNAs might be a novel promising candidate for the treatment of blind‐causing RNV. [ABSTRACT FROM AUTHOR]

We propose an integral imaging 3D display based on top‐hat diffusing screen. The integral imaging 3D display consists of a 2D display, a micro‐lens array, and a top‐hat diffusing screen. The top‐hat diffusing screen is composed of multiple elemental lenses with different pitches. The light rays pass through the top‐hat diffusing screen to form a regular light spot, and the light intensity distribution of the light spot is top‐hat type. This can make the 3D image smooth and natural. The experimental results verify the feasibility of the proposed integral imaging 3D display. [ABSTRACT FROM AUTHOR]

Substantial studies have investigated the social influence effect; however, how individuals with different social value orientations (SVOs), prosocials and proselfs, respond to different social influences remains unknown. This study examines the impact of positive and negative social information on the responses of people with different SVOs. A face‐attractiveness assessment task was employed to investigate the relationships between influence probability, memory, and event‐related potentials of social influence. A significant interactional effect suggested that prosocials and proselfs reacted differently to positive (group rating was more attractive) and negative (group rating was less attractive) social influences. Specifically, proselfs demonstrated significantly higher influence probability, marginally better recall performance, smaller N400, and larger late positive potential on receiving negative influence information than on receiving positive influence information, while prosocials showed no significant differences. Overall, correlations between N400/LPP, influence probability, and recall performance were significant. The above results indicate the modulating role of SVO when responding to social influence. These findings have important implications for understanding how people conform and how prosocial behavior occurs. [ABSTRACT FROM AUTHOR]

Introduction: To test the utility of the "A/T/N" system in the Chinese population, we study core Alzheimer's disease (AD) biomarkers in a newly established Chinese cohort. Methods: A total of 411 participants were selected, including 96 cognitively normal individuals, 94 patients with mild cognitive impairment (MCI) patients, 173 patients with AD, and 48 patients with non‐AD dementia. Fluid biomarkers were measured with single molecule array. Amyloid beta (Aβ) deposition was determined by 18F‐Flobetapir positron emission tomography (PET), and brain atrophy was quantified using magnetic resonance imaging (MRI). Results: Aβ42/Aβ40 was decreased, whereas levels of phosphorylated tau (p‐tau) were increased in cerebrospinal fluid (CSF) and plasma from patients with AD. CSF Aβ42/Aβ40, CSF p‐tau, and plasma p‐tau showed a high concordance in discriminating between AD and non‐AD dementia or elderly controls. A combination of plasma p‐tau, apolipoprotein E (APOE) genotype, and MRI measures accurately predicted amyloid PET status. Discussion: These results revealed a universal applicability of the "A/T/N" framework in a Chinese population and established an optimal diagnostic model consisting of cost‐effective and non‐invasive approaches for diagnosing AD. [ABSTRACT FROM AUTHOR]

Somatosensory neurons are highly heterogeneous with distinct types of neural cells responding to specific stimuli. However, the distribution and roles of cell‐type‐specific long intergenic noncoding RNAs (lincRNAs) in somatosensory neurons remain largely unexplored. Here, by utilizing droplet‐based single‐cell RNA‐seq (scRNA‐seq) and full‐length Smart‐seq2, we show that lincRNAs, but not coding mRNAs, are enriched in specific types of mouse somatosensory neurons. Profiling of lincRNAs from single neurons located in dorsal root ganglia (DRG) identifies 200 lincRNAs localized in specific types or subtypes of somatosensory neurons. Among them, the conserved cell‐type‐specific lincRNA CLAP associates with pruritus and is abundantly expressed in somatostatin (SST)‐positive neurons. CLAP knockdown reduces histamine‐induced Ca2+ influx in cultured SST‐positive neurons and in vivo reduces histamine‐induced scratching in mice. In vivo knockdown of CLAP also decreases the expression of neuron‐type‐specific and itch‐related genes in somatosensory neurons, and this partially depends on the RNA binding protein MSI2. Our data reveal a cell‐type‐specific landscape of lincRNAs and a function for CLAP in somatosensory neurons in sensory transmission. Synopsis: A single‐cell lincRNA landscape of DRG cells is constructed and hundreds of highly expressed lincRNAs are characterized in distinct types and subtypes of mouse DRG neurons. A highly conserved lincRNA CLAP specifically expressed in somatostatin‐positive neurons regulates histamine‐mediated neuronal activation, acute itch, and type‐specific gene expression. scRNA‐seq reveals that hundreds of lincRNAs are preferentially enriched in the specific type and subtype of somatosensory neurons.Knockdown of CLAP, a conserved and abundant lincRNA in somatostatin‐positive neurons, reduces histamine‐induced neuronal activation and itch sensation.In vivo repression of CLAP reduces neuron type‐specific and itch‐related gene expression, and this partially depends on the RNA binding protein MSI2. [ABSTRACT FROM AUTHOR]

Background: The characteristics of static functional network connectivity (sFNC) and dynamic FNC (dFNC) in neurologically asymptomatic patients undergoing maintenance hemodialysis are unknown. Elucidating these characteristics may improve our understanding of the mechanisms of neuropathological damage in these patients. Purpose: To explore the static and dynamic characteristics of FNC in neurologically asymptomatic patients undergoing maintenance hemodialysis and the relationship between FNC‐related parameters with the neuropsychological scores and blood biomarkers. Study Type: Retrospective. Population: A total of 23 neurologically asymptomatic patients undergoing maintenance hemodialysis and 25 healthy controls matched for age, sex, and years of education. Field Strength/Sequence: A 3.0 T MRI/functional MRI and three‐dimensional‐T1 structural imaging Assessment: Independent components; spatial map intensity; sFNC and dFNC strengths; and time attribute parameters (mean dwell time, fractional window, and number of transitions) were determined. Neuropsychological tests were performed. Blood biochemical tests were performed for the patients but not healthy controls. Statistical Tests: Chi‐squared test, one‐sample t‐test, two‐sample t‐test, partial correlation analysis, and family‐wise error and false discovery rate correction. P < 0.05 denoted statistical significance. Results: Significant group differences in the strengths of sFNC and dFNC between networks were found. The sFNC strength between the visual and sensorimotor networks was significantly associated with the global cognitive function score (i.e. the Montreal Cognitive Assessment [MoCA]) (r = 0.606). The sFNC strength between the salience and default mode networks was significantly associated with anxiety scores (r = 0.458). In state 1, positive correlations were found between the mean dwell time and backward digital span task score (r = 0.562), fractional window and MoCA score (r = 0.576), and fractional window and backward digital span task score (r = 0.592). Data Conclusion: Neurologically asymptomatic patients undergoing maintenance hemodialysis had defective sFNC and dFNC. Our results provide a new perspective on the mechanism of neuropathological damage in patients undergoing maintenance hemodialysis. Evidence Level: 1 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

This research attempted to screen potential signatures associated with KIRC progression and overall survival by weighted gene co‐expression network analysis (WGCNA) and Cox regression. The KIRC‐associated mRNA expression and clinical data were accessed from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were screened by differential analysis. A co‐expression network was constructed by "WGCNA". Based on WGCNA module, GO and KEGG analyses were performed. Protein–protein interaction (PPI) network was constructed. Prognostic signatures were screened by Lasso‐Cox regression. Prognostic model was evaluated by Receiver Operating Characteristic (ROC) and Kaplan‐Meier (K‐M) curves. Multivariate Cox and nomogram were introduced to examine whether risk score could be an independent marker. qRT‐PCR was introduced to determine expression of 9 hub genes in KIRC clinical tumor tissues and adjacent tissues, respectively. Genes in the green module were highly associated with clinical status, and green module genes were significantly enriched in mitotic nuclear division, cell cycle, and p53 signaling pathway. Twenty‐six candidates were subsequently screened out from the green module. Next, a 9‐gene prognostic model (DLGAP5, NUF2, TOP2A, RRM2, HJURP, PLK1, AURKB, KIF18A, CCNB2) was constructed. The predicting ability of the model was optimal. Some cancer‐related signaling pathways were differently activated between two risk score groups. Additionally, under‐expression of some signature genes (AURKB, CCNB2, PLK1, RRM2, TOP2A) was associated with better survival rate for KIRC patients. Meanwhile, all 9 hub genes were substantially overexpressed in KIRC patients. A KIRC prognostic signature was screened in this study, contributing valuable findings to KIRC biomarker development. [ABSTRACT FROM AUTHOR]

To control the ongoing COVID‐19 pandemic, a variety of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines have been developed. However, the rapid mutations of SARS‐CoV‐2 spike (S) protein may reduce the protective efficacy of the existing vaccines which is mainly determined by the level of neutralizing antibodies targeting S. In this study, we screened prevalent S mutations and constructed 124 pseudotyped lentiviral particles carrying these mutants. We challenged these pseudoviruses with sera vaccinated by Sinovac CoronaVac and ZF2001 vaccines, two popular vaccines designed for the initial strain of SARS‐CoV‐2, and then systematically assessed the susceptivity of these SARS‐CoV‐2 variants to the immune sera of vaccines. As a result, 14 S mutants (H146Y, V320I + S477N, V382L, K444R, L455F + S477N, L452M + F486L, F486L, Y508H, P521R, A626S, S477N + S698L, A701V, S477N + T778I, E1144Q) were found to be significantly resistant to neutralization, indicating reduced protective efficacy of the vaccines against these SARS‐CoV‐2 variants. In addition, F486L and Y508H significantly enhanced the utilization of human angiotensin‐converting enzyme 2, suggesting a potentially elevated infectivity of these two mutants. In conclusion, our results show that some prevalent S mutations of SARS‐CoV‐2 reduced the protective efficacy of current vaccines and enhance the infectivity of the virus, indicating the necessity of vaccine renewal and providing direction for the development of new vaccines. [ABSTRACT FROM AUTHOR]

Increasing evidence supports inter‐species transmission of SARS‐CoV‐2 variants from humans to domestic or wild animals during the ongoing COVID‐19 pandemic, which is posing great challenges to epidemic control. Clarifying the host range of emerging SARS‐CoV‐2 variants will provide instructive information for the containment of viral spillover. The spike protein (S) of SARS‐CoV‐2 is the key determinant of receptor utilization, and therefore amino acid mutations on S will probably alter viral host range. Here, to evaluate the impact of S mutations, we tested 27 pseudoviruses of SARS‐CoV‐2 carrying different spike mutants by infecting Hela cells expressing different angiotensin‐converting enzyme 2 (ACE2) orthologs from 20 animals. Of these 27 pseudoviruses, 20 bear single mutation and the other 7 were cloned from emerging SARS‐CoV‐2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (B.1.429), and Mu (B.1.621). Using pseudoviral reporter assay, we identified that the substitutions of T478I and N501Y enabled the pseudovirus to utilize chicken ACE2, indicating potential infectivity to avian species. Furthermore, the S mutants of real SARS‐CoV‐2 variants comprising N501Y showed significantly acquired abilities to infect cells expressing mouse ACE2, indicating a critical role of N501Y in expanding SARS‐CoV‐2 host range. In addition, A262S and T478I significantly enhanced the utilization of various mammal ACE2. In summary, our results indicated that T478I and N501Y substitutions were two S mutations important for receptor adaption of SARS‐CoV‐2, potentially contributing to the spillover of the virus to many other animal hosts. Therefore, more attention should be paid to SARS‐CoV‐2 variants with these two mutations. [ABSTRACT FROM AUTHOR]

SUMMARY: Oilseed crops are used to produce vegetable oil to satisfy the requirements of humans and livestock. Cotton (Gossypium spp.) is of great economic value because it is used as both an important textile commodity and a nutrient‐rich resource. Cottonseed oil is rich in polyunsaturated fatty acids and does not contain trans fatty acids; hence, it is considered a healthy vegetable oil. However, research on the genetic basis for cottonseed protein content, oil production, and fatty acid composition is lacking. Here, we investigated the protein content, oil content, and fatty acid composition in terms of oleic acid (C18:1) and linoleic acid (C18:2) in mature cottonseeds from 318 Gossypium hirsutum accessions. Moreover, we examined the dynamic change of protein content and lipid composition including palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1), linoleic acid (C18:2), and linolenic acid (C18:3) in developing seeds from 258 accessions at 10 and 20 days post‐anthesis. Then, we conducted a genome‐wide association study and identified 152 trait‐associated loci and 64 candidate genes responsible for protein and oil‐related contents in mature cottonseeds and ovules. Finally, six candidate genes were experimentally validated to be involved in the regulation of fatty acid biosynthesis through heterologous expression in Arabidopsis. These results comprise a solid foundation for expanding our understanding of lipid biosynthesis in cotton, which will help breeders manipulate protein and oil contents to make it a fully developed 'fiber, food, and oil crop'. Significance Statement: Knowledge of the genetic basis for cottonseed protein content, oil production, and fatty acid composition is still limited. This study addresses the dynamic change of protein content and lipid composition in hundreds of upland cotton (Gossypium hirsutum) accessions and identifies loci and genes regulating cottonseed oil and protein synthesis and accumulation. [ABSTRACT FROM AUTHOR]

Increasing electrode thickness can substantially enhance the specific energy of lithium‐ion batteries; however, ionic transport, electronic conductivity, and ink rheology are current barriers to adoption. Here, a novel approach using a mixed xanthan gum and locust bean gum binder to construct ultra‐thick electrodes is proposed to address above issues. After combining aqueous binder with single‐walled carbon nanotubes (SWCNT), active material (LiNi0.8Co0.1Mn0.1O2) and subsequent vacuum freeze‐drying, highly aligned, and low‐tortuosity structures with a porosity of ca. 50% can be achieved with an average pore size of 10 μm, whereby the gum binder‐SWCNT‐NMC811 forms vertical structures supported by tissue‐like binder/SWCNT networks allowing for excellent electronic conducting phase percolation. As a result, ultra‐thick electrodes with a mass loading of about 511 mg cm−2 and 99.5 wt% active materials have been demonstrated with a remarkable areal capacity of 79.3 mAh cm−2, which is the highest value reported so far. This represents a >25× improvement compared with conventional electrodes with an areal capacity of about 3 mAh cm−2. This route also can be expanded to other electrode materials, such as LiFePO4 and Li4Ti5O12, and thus opens the possibility for low‐cost and sustainable ultra‐thick electrodes with increased specific energy for future lithium‐ion batteries. [ABSTRACT FROM AUTHOR]

Numerous microRNAs (miRs) are abnormally expressed in response to hypoxia‐induced myocardial damage. Herein, miR‐34c‐5p as a potential pharmaco‐target was investigated in a mouse model of chronic intermittent hypoxia (CIH)‐induced myocardial damage. A mouse model of myocardial damage was established using CIH with 7% or 21% O2 alternating 60 s for 12 h/day, 21% O2 for 12 h/day. AntagomiR‐34c‐5p (20 nM/0.1 ml; once a week for 12 weeks) was used as a miR‐34c‐5p inhibitor in a mouse model with tail‐vein injection. In another experiment, mice were administrated with Sirt1 activator SRT1720 (50 mg/kg/day) by intraperitoneal injection. Gene Expression Omnibus database showed a significant upregulation of miR‐34c‐5p expression in the ischemic myocardium of male mice. In CIH‐stimulated mice, miR‐34c‐5p expression was also significantly increased compared with normal mice. Treatment of antagomiR‐34c‐5p significantly restrained CIH‐triggered myocardial apoptosis. After administration of antagomiR‐34c‐5p or Sirt1 activator SRT1720, cardiac hypertrophy and oxidative stress were attenuated in CIH‐stimulated mice. We also found sirtuin 1 (Sirt1) as a direct target of miR‐34c‐5p, which was able to mediate Sirt1 protein expression in cardiomyocytes. AntagomiR‐34c‐5p injection markedly elevated Sirt1 protein expression in CIH‐stimulated mice. AntagomiR‐34c‐5p or Sirt1 activator SRT1720 administration exhibited the antioxidative activity and cardioprotective roles in CIH‐stimulated mice. [ABSTRACT FROM AUTHOR]

Nucleotide‐binding leucine‐rich repeat (NLR) proteins work as crucial intracellular immune receptors. N‐terminal domains of NLRs fall into two groups, coiled‐coil (CC) and Toll‐interleukin 1 receptor domains, which play critical roles in signal transduction and disease resistance. However, the activation mechanisms of NLRs, and how their N‐termini function in immune induction, remain largely unknown. Here, we revealed that the CC domain of a rice NLR Pit contributes to self‐association. The Pit CC domain possesses three conserved hydrophobic residues that are known to be involved in oligomer formation in two NLRs, barley MLA10 and Arabidopsis RPM1. Interestingly, the function of these residues in Pit differs from that in MLA10 and RPM1. Although three hydrophobic residues are important for Pit‐induced disease resistance against rice blast fungus, they do not participate in self‐association or binding to downstream signalling molecules. By homology modelling of Pit using the Arabidopsis ZAR1 structure, we tried to clarify the role of three conserved hydrophobic residues and found that they are located in the predicted α2‐helix of the Pit CC domain and involved in the plasma membrane localization. Our findings provide novel insights for understanding the mechanisms of NLR activation as well as the relationship between subcellular localization and immune induction. Summary Statement: N‐terminal coiled‐coil (CC) or Toll‐interleukin 1 receptor (TIR) domains of nucleotide‐binding leucine‐rich repeats (NLRs) possess pleiotropic functions. Therefore, a deeper understanding of the mode of action of CC and TIR domains of NLRs helps us to decipher how NLRs trigger plant immunity. This paper clarified the role of the three highly conserved hydrophobic residues in the predicted α2‐helix in the CC domain of a rice NLR protein Pit using the ArabidopsisZAR1 structure. These three residues participate in Pit's plasma membrane localization and play key roles in disease resistance to rice blast fungus. Our findings provide novel insights for understanding the mechanisms of NLR activation. [ABSTRACT FROM AUTHOR]

In this paper, a calculation method of color amplitude‐only computer‐generated hologram (CGH) that can suppress speckle noise is proposed. Firstly, the amplitude information of the red, green and blue channels of the object is extracted. Secondly, to reduce the speckle noise, the convolution result of the amplitude information with a constrained random phase is used as the complex amplitude distribution of the object. Then, the multi‐frame amplitude‐only CGHs for each color channel of the object are generated by using the modified double‐step Fresnel diffraction algorithm. Finally, the digital micromirror device is used to refresh the multi‐frame amplitude‐only CGHs, and the speckle noise is suppressed by using the time‐averaging method. The validity of the computational method is verified. [ABSTRACT FROM AUTHOR]

Introduction: Parents who have lost their only child and over the age of 60 are known as elderly shidu parents. This study aimed to investigate predictors of prolonged grief disorder (PGD) among Chinese elderly shidu parents. Methods: Two hundred and ninety‐eight elderly shidu parents from Shenyang were included in this cross‐sectional study. Participants completed a questionnaire including the Prolonged Grief questionnaire‐13 (PG‐13), the PTSD (post‐traumatic stress disorder) Checklist for DSM‐5 (PCL‐5), the Center for Epidemiologic Studies Depression Scales (CES‐D), the Self‐Rating Anxiety Scale (SAS), and the Perceived Stress Scale‐10 (PSS‐10). Multiple linear regression was used to examine socio‐demographic, bereavement‐related and perceived stress associated with PGD symptoms. Results: The prevalence of PGD among Chinese elderly shidu parents was 13.8%. Among the 41 PGD patients, 29, 39, 36 patients had comorbidity of PTSD, depressive symptoms and anxiety, respectively. Perceived stress, higher educational level, lower annual household income, perceived stigma, violent death of the child, and being in debt were associated with severer PGD symptoms. Discussion: The present study revealed the prevalence of PGD and the important role of PGD in diagnosing other mental disorders in Chinese elderly shidu parents. Providing financial help, eliminating social stigma, and stress should be included in PGD prevention among Chinese elderly shidu parents. [ABSTRACT FROM AUTHOR]

Li metal has been attracting considerable attention as the most promising anode material for application in next‐generation Li rechargeable batteries. However, the instability of the formed solid electrolyte interphase (SEI) in the Li metal anode leads to a low coulombic efficiency (CE). Here, two kinds of synthesized polymer materials with different molecular configurations (chain and cross‐linked), which are grafted as skins on Cu foils (current collectors), are reported. The interaction between the polymers and electrolyte solvent reduces the amount of the solvent used in the formation of the SEI layer, while facilitating the decomposition of Li salts; this results in inorganic‐component‐dominated SEI layers with excellent stability. Furthermore, the Cu foil grafted with the polymer has a cross‐linked structure that results in an SEI layer that exhibits a combination of rigidity and flexibility. The SEI layer improves the average CE of the Li/Cu batteries to 98.7% over 550 cycles. A Li/Li symmetric battery assembled with 10 µm ultrathin Li anodes achieves prolonged cycling for 1300 h at a current density of 3 mA cm−2. The ultrathin Li anodes can be applied to Li/S batteries, highlighting a new approach to the design of future batteries. [ABSTRACT FROM AUTHOR]

Metabolic rewiring is one of the indispensable drivers of epithelial--mesenchymal transition (EMT) involved in breast cancer metastasis. In this study, we explored the metabolic changes during spontaneous EMT in three separately established breast EMT cell models using a proteomic approach supported by metabolomic analysis. We identified common proteomic changes, including the expression of CDH1, CDH2, VIM, LGALS1, SERPINE1, PKP3, ATP2A2, JUP, MTCH2, RPL26L1 and PLOD2. Consistently altered metabolic enzymes included the following: FDFT1, SORD, TSTA3 and UDP-glucose dehydrogenase (UGDH). Of these, UGDH was most prominently altered and has previously been associated with breast cancer patient survival. siRNA-mediated knock-down of UGDH resulted in delayed cell proliferation and dampened invasive potential of mesenchymal cells and downregulated expression of the EMT transcription factor SNAI1. Metabolomic analysis revealed that siRNA-mediated knock-down of UGDH decreased intracellular glycerophosphocholine (GPC), whereas levels of acetylaspartate (NAA) increased. Finally, our data suggested that plateletderived growth factor receptor beta (PDGFRB) signalling was activated in mesenchymal cells. siRNA-mediated knock-down of PDGFRB downregulated UGDH expression, potentially via NFkB-p65. Our results support an unexplored relationship between UGDH and GPC, both of which have previously been independently associated with breast cancer progression. [ABSTRACT FROM AUTHOR]

Summary: As the pandemic progresses, the pathophysiology of coronavirus disease 2019 (COVID‐19) is becoming clearer and the potential for immunotherapy is increasing. However, clinical efficacy and safety of immunosuppressants (including tocilizumab, sarilumab and anakinra) treatment in COVID‐19 patients are not yet known. We searched PubMed, Embase Medline, Web of Science and MedRxiv using specific search terms in studies published from 1 January 2020 to 20 December 2020. In total, 33 studies, including 3073 cases and 6502 controls, were selected for meta‐analysis. We found that immunosuppressant therapy significantly decreased mortality in COVID‐19 patients on overall analysis (odds ratio = 0.71, 95% confidence interval = 0.57–0.89, p = 0.004). We also found that tocilizumab and anakinra significantly decreased mortality in patients without any increased risk of secondary infection. In addition, we found similar results in several subgroups. However, we found that tocilizumab therapy significantly increased the risk of fungal co‐infections in COVID‐19 patients. This represents the only systematic review and meta‐analysis to investigate the efficacy and secondary infection risk of immunosuppressant treatment in COVID‐19 patients. Overall, immunosuppressants significantly decreased mortality but had no effect on increased risk of secondary infections. Our analysis of tocilizumab therapy showed a significantly increased risk of fungal co‐infections in these patients. [ABSTRACT FROM AUTHOR]

Mounting evidence suggests that there is a close association between chronic sleep deprivation (CSD) and cognitive deficits. The animal model of CSD‐induced cognitive deficits is commonly used to seek potential treatments. Soy isoflavones (SI) have been reported to possess antioxidant, anti‐inflammation, and neuroprotective effects. In the present study, the effects of SI on CSD‐induced memory impairment were investigated. The mice were subjected to the sleep interruption apparatus and continuously sleep deprived for 2 weeks, while orally administrated with SI (10, 20, and 40 mg/kg) or Modafinil (MOD,100 mg/kg) during the CSD process. Immediately after the SD protocol, cognitive performance of mice was evaluated by the object location recognition (OLR) test, the novel object recognition (NOR) test, and the Morris water maze (MWM) task, as well as the hippocampus, was extracted for evaluation of oxidative stress parameters and inflammation levels through biochemical parameter assay and western blotting analysis. The results showed that SI administration remarkably improved the cognitive performance of CSD‐treated mice in OLR, NOR, and MWM tests. In addition, SI significantly elevated total antioxidant capacity and superoxide dismutase enzyme activities, decreased malondialdehyde level, promoting antioxidant element nuclear erythroid‐2‐related factor 2, and its downstream targets, including heme oxygenase 1, and quinone oxidoreductase 1 protein expressions. Moreover, SI treatment significantly suppressed nuclear factor kappa B p65, nitric oxide synthase, and cyclooxygenase 2 activation, as well as the pro‐inflammatory cytokines (Tumor necrosis factor‐α [TNF‐α], interleukin‐6 [IL‐6], and interleukin‐1β [IL‐1β]) release in the hippocampus of CSD‐treated mice. In summary, the current study provides an insight into the potential of SI in treatment of cognitive deficits by CSD. [ABSTRACT FROM AUTHOR]

Interferon regulatory factor 3 (IRF3)‐induced type I interferon (I‐IFN) production plays key roles in both antiviral and autoimmune responses. IRF3 phosphorylation, dimerization, and nuclear localization are needed for its activation and function, but the precise regulatory mechanisms remain to be explored. Here, we show that the serine/threonine kinase AKT2 interacts with IRF3 and phosphorylates it on Thr207, thereby attenuating IRF3 nuclear translocation in a 14‐3‐3ε‐dependent manner and reducing I‐IFN production. We further find that AKT2 expression is downregulated in viral‐infected macrophages or in monocytes and tissue samples from systemic lupus erythematosus (SLE) patients and mouse models. Akt2‐deficient mice exhibit increased I‐IFN induction and reduced mortality in response to viral infection, but aggravated severity of SLE. Overexpression of AKT2 kinase‐inactive or IRF3‐T207A mutants in zebrafish supports that AKT2 negatively regulates I‐IFN production and antiviral response in a kinase‐dependent manner. This negative role of AKT2 in IRF3‐induced I‐IFN production suggests that AKT2 may be therapeutically targeted to differentially regulate antiviral infection and SLE. Synopsis: Interferon regulatory factor 3 (IRF3)‐induced type I interferon (I‐IFN) production plays key roles during antiviral response and systemic lupus erythematosus (SLE). Here, AKT2 is shown to regulate I‐IFN production by binding to and phosphorylating IRF3 to attenuate IRF3 nuclear translocation, leading to reduced I‐IFN production. AKT2 expression is downregulated in viral‐infected macrophages and in samples from SLE patients and mouse models.I‐IFN stimulation reduces Akt2 transcription and AKT2 inhibits I‐IFN production.AKT2 binds and phosphorylates IRF3 at Thr207 to reduce IRF3 nuclear localization.Akt2 deficiency promotes IFNβ1 production to favor antiviral response while enhancing SLE in mouse models. [ABSTRACT FROM AUTHOR]

The disordered mining of ion‐type rare soil has caused significant ecological and environmental problems. Arbuscular mycorrhizal fungi (AMF) can promote soil quality, providing new ideas about the ecological restoration of degraded soil. In this study, the degraded ion‐type rare earth tailing soils in Xinfeng County, southern Jiangxi Province, was used as a research object. The soil was subjected to different restoration methods (biochar + fly ash + surface vegetation planting) for 2 yr. A total of six treatments were set up in this experiment, and the phospholipid fatty acid method was used to determine the microbial community structure and biomass of the rhizosphere soil of navel oranges [Citrus sinensis (L.) Osbeck] treated with different amounts of biochar (0, 1, and 5%) plus surface mulching (Trifolium repens L.) or soil without plants. Additionally, a pot experiment was conducted to study the effects of single and double inoculation of AMF (Septoglomus viscosum and Claroideoglomus claroideum) on plant growth and soil improvement under various P levels (0 and 50 mg kg–1) in ion‐type rare soil. The results showed that the microbial biomass (fungi, Gram‐positive bacteria, Gram‐negative bacteria, actinomycetes, AMF, and protozoa) when T. repens was present was noticeably higher than that when T. repens was not present. In particular, the biomass of the AMF under the T. repens treatment with 5% biochar (1.28 nmol g–1) was 34.38% higher than that under the 5% biochar treatment without plants (p <.05). Furthermore, the pot experiments showed that AMF inoculation significantly increased the plant biomass, single AMF inoculation significantly increased soil P in the absence of basal P, and double inoculation significantly increased the glomalin (a component of soil organic matter) content. Our findings indicated that the soil microbial biomass was greatly affected by planting T. repens and adding biological modifiers. These composite remediation methods could provide an increasing number of C sources for the soil microbial community and could effectively improve soil quality and plant growth. Core Ideas: We conducted a novel study on the effect of arbuscular mycorrhizal fungi (AMF) on restoration of degraded soil in ionized rare earth mining area.Soil microbial biomass was greatly affected by Trifolium repens and biological modifier.The inoculation of AMF had a significant contribution to the soil organic matter pool.The composite remediation modes could effectively improve soil quality and plant growth. [ABSTRACT FROM AUTHOR]

Background: Tyrophagus putresecentiae is an important mite species in rural and urban environments, causing sensitization and allergic disease. While evidence suggests that microRNAs (miRNAs) may regulate the expression of allergen‐encoding genes, no study has directly investigated this possibility. Here, this gap was addressed by profiling miRNAs and elucidating their target allergen messenger RNAs (mRNAs) in this mite species. Methods: Small RNA and transcriptome libraries were constructed for eggs, larvae, nymphs, and adults. After deep miRNA and whole‐transcriptome sequencing were performed, the miRNA and allergen‐encoding mRNA regulatory networks were explored. Results: A total of 540 miRNAs were identified, including 155 with expression levels differing significantly across the four mite developmental stages (p <.01), 59 of which were novel. The mRNA expression for allergens was higher for Tyr p 1 in adults than in other developmental stages; Tyr p 2–5, 7, 10, 13, 33, and 34 in immature stages; and Tyr p 28, 35, and 36 in eggs and adults. A combined miRNA and transcriptome bioinformatics analysis showed that allergen Tyr p 3 was regulated by miRNA PC‐5p‐5698441_1, Tyr p 4 was regulated by PC‐5p‐7050653_1, and Tyr p 34 was regulated by PC‐5p‐5534223_1 and PC‐5p‐5698441_1. These three allergen mRNA and three miRNAs were identified using qRT‐PCR, and their regulatory roles were confirmed by double‐fluorescent reporter gene system and site‐directed mutagenesis technology. Conclusions: For the first time, allergen mRNA expression and miRNAs were profiled throughout the life cycle for an allergen‐producing mite, and the results showed that miRNAs bind to target allergen mRNAs to regulate their expression. [ABSTRACT FROM AUTHOR]