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LiGaTe 2 is a promising nonlinear optical crystal with a large figure of merit ( d 36 2 / n 3 ), but it is difficult to grow the LiGaTe 2 single crystal due to its extreme instability. In this work, we used Ag to replace Li and successfully grew a Li 0.5 Ag 0.5 GaTe 2 crystal by the modified Bridgman method for the first time. We found it has thermal stability below 200 °C in an atmospheric environment, and the thermal expansion coefficient is positive. This is different from LiGaTe 2 and AgGaTe 2 which have a negative thermal expansion coefficient along the c -axis. When the temperature exceeds 200 °C, Li 0.5 Ag 0.5 GaTe 2 is easily decomposed and oxidized. Under closed vacuum conditions, the melting and solidifying points of Li 0.5 Ag 0.5 GaTe 2 are measured to be 719 and 694 °C. XPS spectra show that the binding energies of Li, Ga, and Te are higher than LiGaTe 2 , and the surface is easily oxidized. The A1 vibration modes are found at 117.72 and 135.44 cm -1 by the Raman spectrum which is related to the Te and Ga-Te bond in [GaTe 4 ] 5- tetrahedra. Li 0.5 Ag 0.5 GaTe 2 has a wide transmittance range from 0.94 to 20 μm, and there was two-photon absorption near 16 μm. The phonon spectrum and PDOS were simulated by the DFT calculation to study the phonon vibration modes in the lattice, which shows that the density of the Raman vibration is higher than those of AgGaTe 2 and LiGaTe 2 . The SHG test results showed that the SHG response intensity of Li 0.5 Ag 0.5 GaTe 2 is 1.5 times that of AgGaS 2 , which shows its excellent nonlinear optical properties for mid-IR applications.

Influenza A viruses have eight genomic RNAs that are transcribed in the host cell nucleus. Two of the viral mRNAs undergo alternative splicing. The M1 mRNA encodes the matrix protein 1 (M1) and is also spliced into M2 mRNA, which encodes the proton channel matrix protein 2 (M2). Our previous studies have shown that the cellular NS1-binding protein (NS1-BP) interacts with the viral non-structural protein 1 (NS1) and M1 mRNA to promote M1 to M2 splicing. Another pool of NS1 protein binds the mRNA export receptor NXF1 (nuclear RNA export factor-1), leading to nuclear retention of cellular mRNAs. Here we show a series of biochemical and cell biological findings that suggest a model for nuclear export of M1 and M2 mRNAs despite the mRNA nuclear export inhibition imposed by the viral NS1 protein. NS1-BP competes with NS1 for NXF1 binding, allowing the recruitment of NXF1 to the M mRNAs after splicing. NXF1 then binds GANP (Germinal-center Associated Nuclear Protein), a member of the TRanscription and EXport complex (TREX)-2. Although both NS1 and NS1-BP remain in complex with GANP-NXF1, they dissociate once this complex docks at the nuclear pore complex (NPC), and the M mRNAs are translocated to the cytoplasm. Since this mRNA nuclear export pathway is key for expression of M1 and M2 proteins that function in viral intracellular trafficking and budding, these viral-host interactions are critical for influenza virus replication., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Exogenous polysulfhydryls (R-SH) supplementation and nitric oxide (NO) gas molecules delivery provide essential antioxidant buffering pool components and anti-inflammatory species in cellular defense against injury, respectively. Herein, the intermolecular disulfide bonds in bovine serum albumin (BSA) molecules were reductively cleaved under native and mild conditions to expose multiple sulfhydryl groups (BSA-SH), then sulfhydryl-nitrosylated (R-SNO), and nanoprecipitated to form injectable self-sulfhydrated, nitro-fixed albumin nanoparticles (BSA-SNO NPs), allowing albumin to act as a NO donor reservoir and multiple sulfhydryl group transporter while also preventing unfavorable oxidation and self-cross-linking of polysulfhydryl groups. In two mouse models of ischemia/reperfusion-induced and endotoxin-induced acute liver injury (ALI), a single low dosage of BSA-SNO NPs ( S -nitrosothiols: 4 μmol·kg -1 ) effectively attenuated oxidative stress and systemic inflammation cascades in the upstream pathophysiology of disease progression, thus rescuing dying hepatocytes, regulating host defense, repairing microcirculation, and restoring liver function. By mechanistically upregulating the antioxidative signaling pathway (Nrf-2/HO-1/NOQ1) and inhibiting the inflammatory cytokine storm (NF-κB/p-IκBα/TNF-α/IL-β), BSA-SNO NPs blocked the initiation of the mitochondrial apoptotic signaling pathway (Cyto C/Bcl-2 family/caspase-3) and downregulated the cell pyroptosis pathway (NLRP3/ASC/IL-1β), resulting in an increased survival rate from 26.7 to 73.3%. This self-sulfhydrated, nitro-fixed functionalized BSA nanoformulation proposes a potential drug-free treatment strategy for ALI.

Developing strategies to target injured pancreatic acinar cells (PACs) in conjunction with primary pathophysiology-specific pharmacological therapy presents a challenge in the management of acute pancreatitis (AP). We designed and synthesized a trypsin-cleavable organosilica precursor bridged by arginine-based amide bonds, leveraging trypsin's ability to selectively identify guanidino groups on arginine via Asp189 at the active S1 pocket and cleave the carboxy-terminal (C-terminal) amide bond via catalytic triads. The precursors were incorporated into the framework of mesoporous silica nanoparticles (MSNs) for encapsulating the membrane-permeable Ca 2+ chelator BAPTA-AM with a high loading content (∼43.9%). Mesenchymal stem cell membrane coating and surface modification with PAC-targeting ligands endow MSNs with inflammation recruitment and precise PAC-targeting abilities, resulting in the highest distribution at 3 h in the pancreas with 4.7-fold more accumulation than that of naked MSNs. The outcomes transpired as follows: After bioinspired MSNs' skeleton biodegradation by prematurely and massively activated trypsin, BAPTA-AM was on-demand released in injured PACs, thereby effectively eliminating intracellular calcium overload (reduced Ca 2+ level by 81.3%), restoring cellular redox status, blocking inflammatory cascades, and inhibiting cell necrosis by impeding the IκBα/NF-κB/TNF-α/IL-6 and CaMK-II/p-RIP3/p-MLKL/caspase-8,9 signaling pathways. In AP mice, a single dose of the formulation significantly restored pancreatic function (lipase and amylase reduced more by 60%) and improved the survival rate from 50 to 91.6%. The formulation offers a potentially effective strategy for clinical translation in AP treatment.

Long non-coding RNA RP11-64B16.4 ( m yocardial i nfarction p rotection- r elated l ncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re-expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta-8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL-mediated anti-apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia-enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Laser-driven dynamic compression experiments of plastic materials have found surprisingly fast formation of nanodiamonds (ND) via X-ray probing. This mechanism is relevant for planetary models, but could also open efficient synthesis routes for tailored NDs. We investigate the release mechanics of compressed NDs by molecular dynamics simulation of the isotropic expansion of finite size diamond from different P-T states. Analysing the structural integrity along different release paths via molecular dynamic simulations, we found substantial disintegration rates upon shock release, increasing with the on-Hugnoiot shock temperature. We also find that recrystallization can occur after the expansion and hence during the release, depending on subsequent cooling mechanisms. Our study suggests higher ND recovery rates from off-Hugoniot states, e.g., via double-shocks, due to faster cooling. Laser-driven shock compression experiments of polyethylene terephthalate (PET) samples with in situ X-ray probing at the simulated conditions found diamond signal that persists up to 11 ns after breakout. In the diffraction pattern, we observed peak shifts, which we attribute to thermal expansion of the NDs and thus a total release of pressure, which indicates the stability of the released NDs., (© 2024. The Author(s).)

There is a gradual transition from water to dryland rearing of geese. In this study, we performed 16S rRNA sequencing (16S rRNA-seq) and transcriptome sequencing (RNA-seq) to reveal the effects of cage rearing (CR) and floor rearing (FR) systems on the microbial composition and transcriptome of the goose ileum. Through 16S rRNA-seq, Linear Discriminant Analysis Effect Size (LEfSe) analysis identified 2 ( hgcI&#95;clade and Faecalibacterium ) and 14 ( Bacteroides , Proteiniphilum , Proteiniclasticum , etc.) differential microbiota in CR and FR, respectively. The rearing system influenced 4 pathways including biosynthesis of amino acids in ileal microbiota. Moreover, we identified 1,198 differentially expressed genes (DEGs) in the ileum mucosa, with 957 genes up-regulated in CR and 241 genes up-regulated in FR. In CR, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the significant enrichment ( p < 0.05) of 28 KEGG pathways, most of which were associated with amino acid metabolism. In FR, up-regulated DEGs were mainly enriched in KEGG pathways associated with cellular processes, including apoptosis, necroptosis, and cellular senescence. Spearman correlation analysis of differential microbiota and amino acid metabolism-related DEGs in CR showed a significant positive correlation. Additionally, differential microbiota of FR, Phascolarctobacterium and Sutterella , were positively correlated with FGF10 ( p < 0.05) and PIK3R1 ( p < 0.01), respectively. In conclusion, there might be differences in ileal amino acid metabolism levels between CR and FR geese, and the observed increase in harmful bacterial species in FR might impact the activity of ileal cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Li, Zhang, Ouyang, Hu, Hu, He, Li, Liu and Wang.)

Severe acute pancreatitis (AP) is a life-threatening pancreatic inflammatory disease with a high mortality rate (∼40%). Existing pharmaceutical therapies in development or in clinical trials showed insufficient treatment efficacy due to their single molecular therapeutic target, poor water solubility, short half-life, limited pancreas-targeting specificity, etc. Herein, acid-responsive hollow mesoporous Prussian blue nanoparticles wrapped with neutrophil membranes and surface modified with the N , N -dimethyl-1,3-propanediamine moiety were developed for codelivering membrane-permeable calcium chelator BAPTA-AM (BA) and trypsin activity inhibitor gabexate mesylate (Ga). In the AP mouse model, the formulation exhibited efficient recruitment at the inflammatory endothelium, trans -endothelial migration, and precise acinar cell targeting, resulting in rapid pancreatic localization and higher accumulation. A single low dose of the formulation (BA: 200 μg kg -1 , Ga: 0.75 mg kg -1 ) significantly reduced pancreas function indicators to close to normal levels at 24 h, effectively restored the cell redox status, reduced apoptotic cell proportion, and blocked the systemic inflammatory amplified cascade, resulting in a dramatic increase in the survival rate from 58.3 to even 100%. Mechanistically, the formulation inhibited endoplasmic reticulum stress (IRE1/XBP1 and ATF4/CHOP axis) and restored impaired autophagy (Beclin-1/p62/LC3 axis), thereby preserving dying acinar cells and restoring the cellular "health status". This formulation provides an upstream therapeutic strategy with clinical translation prospects for AP management through synergistic ion homeostasis regulation and pancreatic autodigestion inhibition.

Age at first egg (AFE) has consistently garnered interest as a crucial reproductive indicator within poultry production. Previous studies have elucidated the involvement of the hypothalamic-pituitary-ovarian (HPO) and hypothalamic-pituitary-thyroid (HPT) axes in regulating poultry sexual maturity. Concurrently, there was evidence suggesting a potential co-regulatory relationship between these 2 axes. However, as of now, no comprehensive exploration of the key pathways and genes responsible for the crosstalk between the HPO and HPT axes in the regulation of AFE has been reported. In this study, we conducted a comparative analysis of morphological differences and performed transcriptomic analysis on the hypothalamus, pituitary, thyroid, and ovarian stroma between normal laying group (NG) and abnormal laying group (AG). Morphological results showed that the thyroid index difference (D-) value (thyroid index D-value=right thyroid index-left thyroid index) was significantly (P < 0.05) lower in the NG than in the AG, while the ovarian index was significantly (P < 0.01) higher in the NG than in the AG. Furthermore, between NG and AG, we identified 99, 415, 167, and 1182 differentially expressed genes (DEGs) in the hypothalamus, pituitary, thyroid, and ovarian stroma, respectively. Gene ontology (GO) analysis highlighted that DEGs from 4 tissues were predominantly enriched in the "biological processes" category. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that 16, 14, 3, and 26 KEGG pathways were significantly enriched (P < 0.05) in the hypothalamus, pituitary, thyroid, and ovarian stroma. The MAPK signaling pathway emerged as the sole enriched pathway across all 4 tissues. Employing an integrated analysis of the protein-protein interaction (PPI) network and correlation analysis, we found GREB1 emerged as a pivotal component within the HPO axis to regulate estrogen-related signaling in the HPT axis, meanwhile, the HPT axis influenced ovarian development by regulating thyroid hormone-related signaling mainly through OPN5. Then, 10 potential candidate genes were identified, namely IGF1, JUN, ERBB4, KDR, PGF, FGFR1, GREB1, OPN5, DIO3, and THRB. These findings establish a foundation for elucidating the physiological and genetic mechanisms by which the HPO and HPT axes co-regulate goose AFE., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Due to the demands for both environmental protection and modernization of the goose industry in China, the traditional goose waterside rearing systems have been gradually transitioning to the modern intensive dryland rearing ones, such as the net-floor mixed rearing system (MRS) and cage rearing system (CRS). However, the goose immune responses to different dryland rearing systems remain poorly understood. This study aimed to investigate and compare the age-dependent effects of MRS and CRS on the splenic histomorphological characteristics and immune-related genes expression profiles among three economically important goose breeds, including Sichuan White goose (SW), Gang goose (GE), and Landes goose (LD). Morphological analysis revealed that the splenic weight and organ index of SW were higher under CRS than under MRS ( p  < 0.05). Histological observations showed that for SW and LD, the splenic corpuscle diameter and area as well as trabecular artery diameter were larger under MRS than under CRS at 30 or 43 weeks of age ( p  < 0.05), while the splenic red pulp area of GE was larger under CRS than under MRS at 43 weeks of age ( p  < 0.05). Besides, at 43 weeks of age, higher mRNA expression levels of NGF , SPI1 , and VEGFA in spleens of SW were observed under MRS than under CRS ( p  < 0.05), while higher levels of HSPA2 and NGF in spleens of LD were observed under MRS than under CRS ( p  < 0.05). For GE, there were higher mRNA expression levels of MYD88 in spleens under CRS at 30 weeks of age ( p  < 0.05). Moreover, our correlation analysis showed that there appeared to be more pronounced positive associations between the splenic histological parameters and expression levels of several key immune-related genes under MRS than under CRS. Therefore, it is speculated that the geese reared under MRS might exhibit enhanced immune functions than those under CRS, particularly for SW and LD. Although these phenotypic differences are assumed to be associated with the age-dependent differential expression profiles of HSPA2 , MYD88 , NGF , SPI1 , and VEGFA in the goose spleen, the underlying regulatory mechanisms await further investigations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Song, He, Yang, Wang, Li, Wang, Yuan, Hu, He, Li, Wang and Hu.)

Physical inactivity and sarcopenia are potentially modifiable risk factors for falls in older adults, but the strength of the association between physical activity (PA), sarcopenia, and falls in Chinese older adults is unclear. This study sought to investigate the potential mediation mechanism relationship in the connection between PA, sarcopenia, including its elements (muscle strength, physical performance, and skeletal muscle mass), and falls among Chinese older people. The subjects were 3592 community-dwelling Chinese aged 60 or over, selected from the China Health and Retirement Longitudinal Study (CHARLS). PA was evaluated through the International Physical Activity Questionnaire (IPAQ), and sarcopenia was determined through the Asian Working Group on Sarcopenia (AWGS) 2019 guidelines. We employed logistic regression to explore the link between physical activity, sarcopenia, and falls. Additionally, we applied Karlson, Holm and Breen's (KHB) method to estimate two different mediation models. The results demonstrated that PA lowers the risk of falls [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.48-0.61], whereas sarcopenia increases the risk of falls (OR 1.34, 95% CI 1.16-1.55). Sarcopenia mediated the association between PA and falls, explaining a total of 2.69% of the association (indirect effect = -0.02). PA also had a significant mediating effect on the association between sarcopenia and falls, explaining a total of 20.12% of the association (indirect effect = 0.06). The proportion mediated by sarcopenia was 2.69% for PA and falls (indirect effect = -0.02). Our findings suggest that PA and sarcopenia have a direct effect on falls as well as an indirect effect through each other. Enhancing PA levels and preventing sarcopenia may help prevent falls in older adults.

Marine resources in unique marine environments provide abundant, cost-effective natural biomaterials with distinct structures, compositions, and biological activities compared to terrestrial species. These marine-derived raw materials, including polysaccharides, natural protein components, fatty acids, and marine minerals, etc., have shown great potential in preparing, stabilizing, or modifying multifunctional nano-/micro-systems and are widely applied in drug delivery, theragnostic, tissue engineering, etc. This review provides a comprehensive summary of the most current marine biomaterial-based nano-/micro-systems developed over the past three years, primarily focusing on therapeutic delivery studies and highlighting their potential to cure a variety of diseases. Specifically, we first provided a detailed introduction to the physicochemical characteristics and biological activities of natural marine biocomponents in their raw state. Furthermore, the assembly processes, potential functionalities of each building block, and a thorough evaluation of the pharmacokinetics and pharmacodynamics of advanced marine biomaterial-based systems and their effects on molecular pathophysiological processes were fully elucidated. Finally, a list of unresolved issues and pivotal challenges of marine-derived biomaterials applications, such as standardized distinction of raw materials, long-term biosafety in vivo, the feasibility of scale-up, etc., was presented. This review is expected to serve as a roadmap for fundamental research and facilitate the rational design of marine biomaterials for diverse emerging applications., (© 2023. The Author(s).)

The critical challenges in repairing oral soft and hard tissue defects are infection control and the recovery of functions. Compared to conventional tissue regeneration methods, nano-bioactive materials have become the optimal materials with excellent physicochemical properties and biocompatibility. Dental-derived mesenchymal stem cells (DMSCs) are a particular type of mesenchymal stromal cells (MSCs) with great potential in tissue regeneration and differentiation. This paper presents a review of the application of various nano-bioactive materials for the induction of differentiation of DMSCs in oral and maxillofacial restorations in recent years, outlining the characteristics of DMSCs, detailing the biological regulatory effects of various nano-materials on stem cells and summarizing the material-induced differentiation of DMSCs into multiple types of tissue-induced regeneration strategies. Nanomaterials are different and complementary to each other. These studies are helpful for the development of new nanoscientific research technology and the clinical transformation of tissue reconstruction technology and provide a theoretical basis for the application of nanomaterial-modified dental implants. We extensively searched for papers related to tissue engineering bioactive constructs based on MSCs and nanomaterials in the databases of PubMed, Medline, and Google Scholar, using keywords such as "mesenchymal stem cells", "nanotechnology", "biomaterials", "dentistry" and "tissue regeneration". From 2013 to 2023, we selected approximately 150 articles that align with our philosophy., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Li et al.)

Objective: A recent high-throughput sequencing showed that circular RNA Rho-associated kinase 1 (circROCK1) is abnormally highly expressed in sepsis, but whether it is involved in sepsis development remains unclear. The objective of this study was to investigate the biological function of circROCK1 in sepsis-induced myocardial injury and reveal its potential downstream molecular mechanism., Methods: Real-time reverse transcriptase-polymerase chain reaction was applied to detect circROCK1 and miR-96-5p expressions in the serum of septic patients. Spearman correlation analysis examined the correlation between circROCK1 and the clinicopathological characteristics of septic patients. The Cecal puncture and ligation (CLP) method was used to establish an in vivo sepsis model. circROCK1 and miR-96-5p expressions in mice were modified by injection of lentivirus or oligonucleotide. The left ventricular systolic pressure, left ventricular end-diastolic pressure, and the maximum increase/decrease rate of left ventricular pressure were checked. ELISA was applied to detect inflammatory factors levels as well as myocardial injury markers levels. Hematoxylin and eosin staining was performed to observe pathological changes in myocardial tissues, and Western blot examined phosphorylated nuclear factor (NF)-κB and oxidative stress-responsive 1 (OXSR1) expression. Dual luciferase reporter experiment was conducted to confirm the targeting relationship between circROCK1, OXSR1, and miR-96-5p., Results: circROCK1 and OXSR1 were highly expressed in sepsis and miR-96-5p was under-expressed. circROCK1 was positively correlated with serum creatinine, C-reactive protein, procalcitonin, and sequential organ failure assessment scores in septic patients. Silencing circROCK1 could improve the diastolic and systolic function of CLP mice, as well as myocardial damage, reduce myocardial tissue edema and necrosis, and inhibit inflammatory factor level and phosphorylated NF-κB expression. Down-regulating miR-96-5p promoted myocardial injury in CLP mice. Silencing circROCK1 and miR-96-5p inhibited and promoted OXSR1 expression, respectively. Both circROCK1 and OXSR1 had a targeting relationship with miR-96-5p., Conclusion: CircROCK1 promotes myocardial injury in septic mice by regulating the miR-96-5p/OXSR1 axis, and it can be used as a potential target for treating septic myocardial dysfunction.

Background: Danon disease is characterized by the failure of lysosomal biogenesis, maturation, and function due to a deficiency of lysosomal membrane structural protein (LAMP2)., Methods: The current report describes a female patient with a sudden syncope and hypertrophic cardiomyopathy phenotype. We identified the pathogenic mutations in patients by whole-exon sequencing, followed by a series of molecular biology and genetic approaches to identify and functional analysis of the mutations., Results: Suggestive findings by cardiac magnetic resonance (CMR), electrocardiogram (ECG), and laboratory examination suggested Danon disease which was confirmed by genetic testing. The patient carried a novel de novo mutation, LAMP2 c.2T>C located at the initiation codon. The quantitative polymerase chain reaction (qPCR) and Western blot (WB) analysis of peripheral blood leukocytes from the patients revealed evidence of LAMP2 haploinsufficiency. Labeling of the new initiation codon predicted by the software with green fluorescent protein followed by fluorescence microscopy and Western blotting showed that the first ATG downstream from the original initiation codon became the new translational initiation codon. The three-dimensional structure of the mutated protein predicted by alphafold2 revealed that it consisted of only six amino acids and failed to form a functional polypeptide or protein. Overexpression of the mutated LAMP2 c.2T>C showed a loss of function of the protein, as assessed by the dual-fluorescence autophagy indicator system. The mutation was confirmed to be null, AR experiments and sequencing results confirmed that 28% of the mutant X chromosome remained active., Conclusion: We propose possible mechanisms of mutations associated with haploinsufficiency of LAMP2: (1) The inactivation X chromosome carrying the mutation was not significantly skewed. However, it decreased in the mRNA level and the expression ratio of the mutant transcripts; (2) The identified mutation is null, and the active mutant transcript fails to translate into the normal LAMP2 proteins. The presence of haploinsufficiency in LAMP2 and the X chromosome inactivation pattern were crucial factors contributing to the early onset of Danon disease in this female patient., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background: Rare diseases have become a major public health concern worldwide. However, detailed epidemiological data are lacking. With the development of the Internet, search queries have played an important role in disease surveillance. In this study, we explored a new method for the epidemiological research on rare diseases, using large-scale online search queries and reported case data. We distilled search logs related to rare diseases nationwide from 2016 to 2019. The case data were obtained from China's national database of rare diseases during the same period., Results: A total of 120 rare diseases were included in this study. From 2016 to 2019, the number of patients with rare diseases estimated using search data and those obtained from the case database showed an increasing trend. Rare diseases can be ranked by the number of search estimated patients and reported patients, and the rankings of each disease in both search and reported case data were generally stable. Furthermore, the disease rankings in the search data were relatively consistent with the reported case data in each year, with more than 50% of rare diseases having a ranking difference of -20 to 20 between the two systems. In addition, the relationship between the disease rankings in the two systems was generally stable over time. Based on the relationship between the disease rankings in the search and reported case data, rare diseases can be classified into two categories., Conclusion: Online search queries may provide an important new resource for detecting rare diseases. Rare diseases can be classified into two categories to guide different epidemiological research strategies., (© 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Li x Ag 1- x GaSe 2 is a new series of solid solution crystals that has a large nonlinear optical (NLO) coefficient and laser-induced damage threshold (LIDT). It has great application prospects in mid-infrared laser frequency conversion. In this work, Li x Ag 1- x GaSe 2 ( x = 0, 0.2, 0.4, 0.5, 0.6, 0.8, and 1) crystals (Φ 16 mm × 40 mm) were grown by the improved Bridgeman method in a four-zone furnace. It is found that the Li x Ag 1- x GaSe 2 ( x = 0.2-0.8) crystals keep the same tetragonal symmetry with AgGaSe 2 and the melting and solidification temperature increase with the Li content. Because the as-grown crystals are almost opaque in the visible-NIR range, an annealing experiment is necessary. After annealing, the transmittance is improved significantly, which can meet the application requirements. The band gap is changed by annealing atmosphere; for instance, the band gap of Li 0.6 Ag 0.4 GaSe 2 annealed in a LiGaSe 2 powder atmosphere increases from 2.35 to 2.56 eV, while the band gap of LiGaSe 2 annealed in vacuum decreases from 3.39 to 3.01 eV. Finally, the Li x Ag 1- x GaSe 2 shows an extreme SHG response, especially Li 0.8 Ag 0.2 GaSe 2 , which has about five times that of LiGaSe 2 , proving the promising NLO properties.

Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis. Long non-coding RNAs (lncRNAs) are a group of protein expression regulators; however, the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear. The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis. We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis. In cultured monocytes, Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation. The differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown. Moreover, overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage differentiation. The role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice. We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression, whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation. To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease, we applied an acute atherosclerosis model in mice. The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice. The results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes, which is involved in atherogenesis., (Copyright © 2023 Di Xiang et al.)

(1) Background: The role of estrogen receptor gene 1 ( ESR1 ) in female reproduction and lipid metabolism has been extensively investigated. However, its contribution to lipid metabolism during the development of poultry follicles remains unclear. (2) Methods: This study aimed to explore the function of ESR1 via overexpressing ( ESR1 ov ) and interfering ( ESR1 si ) with its expression in pre-hierarchical granulosa cells (phGCs) and hierarchical granulosa cells (poGCs). (3) Results: We successfully cloned and obtained an 1866 bp segment of the full-length CDS region of the Sichuan white goose ESR1 gene. In phGCs of the ESR1 ov and ESR1 si groups, there were no significant changes compared to the control group. However, in poGCs, the ESR1 ov group exhibited decreased lipid deposition, triglycerides, and cholesterol compared to the control group, while the ESR1 si group showed increased lipid deposition, triglycerides, and cholesterol. The expression of APOB and PPARα was significantly reduced in the ESR1 ov group compared to the ESR1 ov -NC group. Moreover, significant changes in the expression of ACCα, DGAT1, SCD, CPT1 , and ATGL were observed between the ESR1 si and ESR1 si -NC group. (4) Conclusions: These findings shed light on the function and molecular mechanism of ESR1 in lipid metabolism in goose poGCs, providing a better understanding of the physiological process of goose follicular development.

LiGa 0.5 In 0.5 Se 2 is a new quaternary nonlinear optical crystal for the mid-IR application grown as a mixed crystal of the LiGaSe 2 -LiInSe 2 solid-solution system. It is transparent in the 0.47-14 μm range and has an appropriate bandgap and a lower melting point than LiGaSe 2 and LiInSe 2 . It is more technological about the growth process since its homogeneity range is broader in the phase diagram. In this work, we have synthesized the LiGa 0.5 In 0.5 Se 2 polycrystal by the two-zone temperature method. LiGa 0.5 In 0.5 Se 2 single crystals (Φ26 mm × 50 mm) were grown through the modified Bridgman method with the c -axis seed crystal which has the smallest thermal expansion coefficient of the three main axes in 293-773 K. The crystal structure was studied by X-ray diffraction and the Rietveld refinement method. Due to the low transmittance of the as-grown crystals, a systematic thermal treatment experiment was carried out. In the annealing experiment, the crystal surface is seriously enriched with selenium due to the thermal diffusion of selenium, resulting in the crystal opacity and cracking, while after vacuum quenching at 873 K, the transmittance of the LiGa 0.5 In 0.5 Se 2 crystal wafer was greatly improved, the bandgap shows a large increase from 2.13 to 2.51 eV, and the quenched crystal shows strong SHG response (×1.91 LiGaSe 2 ). The chemical states and vibration modes of surface elements for both conditions were characterized by X-ray photoelectron and Raman spectra. Density functional theory calculations were carried out to simulate the phonon spectrum and phonon density of states, which can help to study the phonon vibration modes in the lattice.

Pyroptosis, systemic inflammation, and mitochondrial apoptosis are the three primary contributors to sepsis's multiple organ failure, the ultimate cause of high clinical mortality. Currently, the drugs under development only target a single pathogenesis, which is obviously insufficient. In this study, an acid-responsive hollow mesoporous polydopamine (HMPDA) nanocarrier that is highly capable of carrying both the hydrophilic drug NAD + and the hydrophobic drug BAPTA-AM, with its outer layer being sealed by the inflammatory targeting peptide PEG-LSA, is developed. Once targeted to the region of inflammation, HMPDA begins depolymerization, releasing the drugs NAD + and BAPTA-AM. Depletion of polydopamine on excessive reactive oxygen species production, promotion of ATP production and anti-inflammation by NAD + replenishment, and chelation of BAPTA (generated by BA-AM hydrolysis) on overloaded Ca 2+ can comprehensively block the three stages of sepsis, i.e., precisely inhibit the activation of pyroptosis pathway (NF-κB-NLRP3-ASC-Casp-1), inflammation pathway (IL-1β, IL-6, and TNF-α), and mitochondrial apoptosis pathway (Bcl-2/Bax-Cyt-C-Casp-9-Casp-3), thereby restoring intracellular homeostasis, saving the cells in a state of "critical survival," further reducing LPS-induced systemic inflammation, finally restoring the organ functions. In conclusion, the synthesis of this agent provides a simple and effective synergistic drug delivery nanosystem, which demonstrates significant therapeutic potential in a model of LPS-induced sepsis., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The meat and egg of goose is one of the main components of human food supply. The improvement of goose egg production is particularly important for the increasing human population. However, limited information is available about the effective molecular markers and mechanisms of egg production in goose. In this study, we jointly utilized the data of genome resequencing in different egg production Sichuan white goose and transcriptome at different follicle development stages to identified the molecular markers and mechanisms of egg production. The coefficient of variation of individual egg production in Sichuan white goose population is 0.42 to 0.49. Fifty individuals with the highest (laying 365 days egg number, LEN365 = 79-145) and 50 individuals with the lowest (LEN365 = 8-48) egg production were divided into high and low egg production groups. Based on whole-genome sequencing data of the selected samples, 36 SNPs (annotation novel.12.470, CELF2, ATP1A1, KCNJ6, RAB4A, UST, REV3L, DHX15, CAVN2, SLC5A9, Cldn5, MRPS23, and Tspan2) associated with the LEN365 were identified, involving multiple pathways such as metabolism and endocrinology. Notably, 5 SNPs located in the exon9 of ATP1A1 were identified by GWAS analysis. The association analysis with LEN365 showed the phenotypic variance explained of this haplotype consisting of 5 SNPs is 20.51%. Through transcriptome data analysis, we found the expression of ATP1A1 in the granular layers was increased in the stage of small yellow follicle to large yellow follicle (LYF) and LYF to F5, while decreased in F2 to F1. For the first time, we report the haplotype region formed by 5 SNPS on exon9 of ATP1A1 is associated with egg production in goose and involved in follicle selection and maturation processes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Calcium overload and ROS overproduction, two major triggers of acute kidney injury (AKI), are self-amplifying and mutually reinforcing, forming a complicated cascading feedback loop that induces kidney cell "suicide" and ultimately renal failure. There are currently no clinically effective drugs for the treatment of AKI, excluding adjuvant therapy. In this study, a porous silicon-based nanocarrier rich in disulfide bond skeleton (<50 nm) is developed that enables efficient co-loading of the hydrophilic drug borane amino complex and the hydrophobic drug BAPTA-AM, with its outer layer sealed by the renal tubule-targeting peptide PEG-LTH. Once targeted to the kidney injured site, the nanocarrier structure collapses in the high glutathione environment of the early stage of AKI, releasing the drugs. Under the action of the slightly acidic inflammatory environment and intracellular esterase, the released drugs produce hydrogen and BAPTA, which can rapidly eliminate the excess ROS and overloaded Ca 2+ , blocking endoplasmic reticulum/mitochondrial apoptosis pathway (ATF4-CHOP-Bax axis, Casp-12-Casp-3 axis, Cyt-C-Casp-3 axis) and inflammatory pathway (TNF-α-NF-κB axis) from the source, thus rescuing the renal cells in the "critical survival" state and further restoring the kidney function. Overall, this nanoparticle shows substantial clinical promise as a potential therapeutic strategy for I/R injury-related diseases., (© 2023 Wiley-VCH GmbH.)

The currently established DNA nanoprobes for the detection of mycotoxin from beverages have been limited by complicated sample pretreatment and uncontrollable nanoparticle flocculation in complex systems. We develop a rapid colorimetric approach for ochratoxin A (OTA) detection in Baijiu in a sample-in/"yes" or "no" answer-out fashion through target-modulated base pair stacking assembly of DNA-functionalized gold nanoparticles (DNA-AuNPs). The colorimetric signification of OTA relies on the competition of OTA with the AuNP surface-grafted DNA in binding with an OTA-targeted aptamer. The specific recognition of OTA by the aptamer prevents DNA duplex formation on the AuNP surface, thereby inhibiting the base pair stacking assembly of the DNA-AuNPs and giving rise to a "turn-on" color. By further suppressing DNA hybridization using a bulged loop design and an alcohol solution, the DNA-AuNPs exhibit an improved reproducibility for OTA sensing while maintaining excellent susceptivity to OTA. A detection limit of 88 nM was achieved along with high specificity towards OTA, which is lower than the maximum tolerated level of OTA in foodstuffs defined by countries worldwide. The entire reaction time, avoiding sample pretreatment, is less than 17 min. The DNA-AuNPs with anti-interference features and sensitive "turn-on" performance promise convenient on-site detection of mycotoxin from daily beverages.

Calcium overload is one of the early determinants of the core cellular events that contribute to the pathogenesis of acute kidney injury (AKI), which include oxidative stress, ATP depletion, calcium overload, and inflammatory response with self-amplifying and interactive feedback loops that ultimately lead to cellular injury and renal failure. Excluding adjuvant therapy, there are currently no approved pharmacotherapies for the treatment of AKI. Using an adipic dihydride linker, we modified the hyaluronic acid polymer chain with a potent antioxidant, bilirubin, to produce an amphiphilic conjugate. Subsequently, we developed a kidney-targeted and reactive oxygen species (ROS)-responsive drug delivery system based on the flash nanocomplexation method to deliver a well-known intracellular calcium chelator, 1,2-bis(2-aminophenoxy)ethane- N , N , N ', N '-tetraacetic acid acetoxymethyl ester (BAPTA-AM, BA), with the goal of rescuing renal cell damage via rapidly scavenging of intracellularly overloaded Ca 2+ . In the ischemia-reperfusion (I/R) induced AKI rat model, a single dose of as-prepared formulation (BA 100 μg·kg -1 ) 6 h post-reperfusion significantly reduced renal function indicators by more than 60% within 12 h, significantly alleviated tissular pathological changes, ameliorated tissular oxidative damage, significantly inhibited apoptosis of renal tubular cells and the expression of renal tubular marker kidney injury molecule 1, etc., thus greatly reducing the risk of kidney failure. Mechanistically, the treatment with BA-loaded NPs significantly inhibited the activation of the ER stress cascade response (IRE1-TRAF2-JNK, ATF4-CHOP, and ATF6 axis) and regulated the downstream apoptosis-related pathway while also reducing the inflammatory response. The BA-loaded NPs hold great promise as a potential therapy for I/R injury-related diseases.

The importance of thyroid-related genes has been repeatedly mentioned in the transcriptome studies of poultry with different laying performance, yet there are few systematic studies to unravel the regulatory mechanisms of the thyroid-ovary axis in the poultry egg production process. In this study, we compared the transcriptome profiles in the thyroid and ovarian stroma between high egg production (GP) and low egg production (DP) ducks, and then revealed the pathways and candidate genes involved in the process. We identified 1,114 and 733 differentially expressed genes (DEGs) in the thyroid and ovarian stroma, separately. The Gene Ontology (GO) analysis showed that a total of 504 and 189 GO terms were identified in the thyroid and ovarian stroma (P < 0.05). Three common GO terms were identified from the top 5 GO terms with the highest significant level in two tissues, including extracellular space, calcium ion binding, and integral component of plasma membrane. The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that 15 and 14 KEGG pathways were significantly (P < 0.05) enriched in the thyroid and ovarian stroma, respectively. And, there were 8 common pathways, including neuroactive ligand-receptor interaction, calcium signaling pathway, ECM-receptor interaction, PPAR signaling pathway, melanogenesis, wnt signaling pathway, vascular smooth muscle contraction, and cytokine-cytokine receptor interaction. Notably, the neuroactive ligand-receptor interaction pathway was the most significantly enriched by the DEGs both in the thyroid and ovarian stroma. The interaction among DEGs enriched in the neuroactive ligand-receptor interaction and ECM-receptor interaction suggested that the thyroid may regulate ovarian development by these genes. Through integrated analysis of the protein-protein interaction (PPI) network and KEGG pathway maps, 9 key DEGs (PTH, THBS2, THBS4, CD36, ADIPOQ, ACSL6, PRKAA2, CRH, and PCK1) were identified, which could play crucial roles in the thyroid to regulate ovarian function and then affect egg-laying performance between GP and DP. This study serves as a basis to explore the molecular mechanism of the thyroid affecting ovarian function and egg production in female ducks and may help to identify molecular markers that can be used for duck genetic selection., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Growing inputs of microplastics into marine sediment have increased significantly the needs for assessment of their potential risks to the marine benthos. A knowledge gap remains with regard to the effect of microplastics on benthos, such as cephalochordates. By employing amphioxus as a model benthic chordate, here we show that exposure to microplastics for 96 h at doses of 1 mg/L and 100 mg/L results in evident accumulation of the polyethylene microplastics. The accumulated microplastics are as much as 0.027% of body weight upon high-dose exposure, causing an abnormal body-bending phenotype that limits the locomotion capability of amphioxus. Mechanistic insight reveals that microplastics can bring about histological damages in gill, intestine and hepatic cecum; In-depth assay of relevant biomarkers including superoxide dismutase, catalase, glutathione, pyruvic acid and total cholesterol indicates the occurrence of oxidative damage and metabolic disorder; Further, microplastics exposure depresses the activity of acetylcholinesterase while allowing the level of acetylcholine to rise in muscle, suggesting the emergence of neurotoxicity. These consequences eventually contribute to the muscle dysfunction of amphioxus. This study rationalizes the abnormal response of the vulnerable notochord to microplastics, signifying the dilemma suffered by the ancient lineage under the emerging threat. Given the enrichment of microplastics through marine food chains, this study also raises significant concerns on the impact of microplastics to other marine organisms, and eventually human beings., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A wound is the pathological change of soft tissue under normal skin caused by various factors, such as collision, contusion, hot crush, avulsion, corrosive chemicals, operations, excessive wound tension after operations, local pressure that cannot be relieved for a long time, liquid immersion, local infection, and rejection reactions caused by allogeneic substances. The skin itself or its underlying soft tissue loses its integrity and continuity, thus losing its normal physiological function. Medical image analysis is a medical term that refers to the interdisciplinary fields of integrated medical imaging, artificial intelligence, digital image processing and analysis, mathematical modeling, and numerical algorithms. According to the time of wound formation, they can be divided into acute and chronic wounds. The common acute wounds include lacerations caused by trauma, surgical incisions, burns, and donor sites formed after skin graft operations. This article mainly studies the role of platelet-rich plasma gel nanocomposites in promoting wound healing. It is proven that ptt-rich plasma gel can significantly promote tissue repair and regeneration and accelerate wound healing in patients with severe burns. The atomic number of the nanocomposite has a better treatment effect on the nanoparticle approach. In this paper, chitosan nanocomposite membrane, nanocomposite algorithm, and the calculation method of enthalpy of formation of high alloy nanomaterials were used to study the role of ptt-rich plasma gel combined chitosan nanocomposite membrane loaded bone marrow stromal cells in promoting wound healing, and its effects were applied to the repair of special site burns, special burns, and different age burns. Good wound repair benefits from the correct treatment of the wound, which directly affects the stability and development of the internal environment. The difference in healing time between the two groups was statistically significant, and the recovery time of the PRP group was 0.001 less than that of the control group. The results showed that the wound healing time of the PRP group was significantly shorter than that of the control group ( P < 0.05); after treatment, the content of VEGF in the wound tissue of the two groups increased, especially in the PRP group; the effective rate of the PRP group was 75.0%, which was higher than 68.8% of the control group. It can play an important role in the regulation of expression and the pathophysiological process of wound healing., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Zhiyu He et al.)

Extreme conditions inside ice giants such as Uranus and Neptune can result in peculiar chemistry and structural transitions, e.g., the precipitation of diamonds or superionic water, as so far experimentally observed only for pure C─H and H 2 O systems, respectively. Here, we investigate a stoichiometric mixture of C and H 2 O by shock-compressing polyethylene terephthalate (PET) plastics and performing in situ x-ray probing. We observe diamond formation at pressures between 72 ± 7 and 125 ± 13 GPa at temperatures ranging from ~3500 to ~6000 K. Combining x-ray diffraction and small-angle x-ray scattering, we access the kinetics of this exotic reaction. The observed demixing of C and H 2 O suggests that diamond precipitation inside the ice giants is enhanced by oxygen, which can lead to isolated water and thus the formation of superionic structures relevant to the planets' magnetic fields. Moreover, our measurements indicate a way of producing nanodiamonds by simple laser-driven shock compression of cheap PET plastics.

Diverse gases (NO, CO, H 2 S, H 2 , etc.) have been widely applied in the medical intervention of various diseases, including cancer, cardiovascular disease, ischemia-reperfusion injury, bacterial infection, etc., attributing to their inherent biomedical activities. Although many gases have many biomedical activities, their clinical use is still limited due to the rapid and free diffusion behavior of these gases molecules, which may cause potential side effects and/or ineffective treatment. Gas-generating nanoplatforms (GGNs) are effective strategies to address the aforementioned challenges of gas therapy by preventing gas production or release at nonspecific sites, enhancing GGNs accumulation at targeted sites, and controlling gas release in response to exogenous (UV, NIR, US, etc.) or endogenous (H 2 O 2 , GSH, pH, etc.) stimuli at the lesion site, further maintaining gas concentration within the effective range and achieving the purpose of disease treatment. This review comprehensively summarizes the advancements of "state-of-the-art" GGNs in the recent three years, with emphasis on the composition, structure, preparation process, and gas release mechanism of the nanocarriers. Furthermore, the therapeutic effects and limitations of GGNs in preclinical studies using cell/animal models are discussed. Overall, this review enlightens the further development of this field and promotes the clinical transformation of gas therapy., (© 2022 Wiley-VCH GmbH.)

Mid-infrared laser in the 2-5 μm wavelength region is in the atmospheric transmission window range, and hence, it has important application prospects in the fields of optoelectronic countermeasures, space communication, environmental remote sensing, and molecular spectroscopy. One of the most promising technological approaches to achieve mid-infrared laser output is based on direct lasing of transition-metal (TM)-doped II-VI chalcogenide crystals. In this work, CdS x Se 1- x and Cr:CdS 0.8 Se 0.2 polycrystals were synthesized by a chemical vapor synthesis method from a stoichiometric mixture of vacuum-sublimed CdS and CdSe. The structure of the synthesized products was analyzed by X-ray diffraction (XRD). Using these synthesized products, CdS x Se 1- x and Cr:CdS 0.8 Se 0.2 single crystals were grown by the physical vapor transport (PVT) method. After annealing, the band gap becomes smaller and the transmission range widens to 17 μm. The composition of the single crystals was determined by energy-dispersive spectrometry (EDS) mapping and XPS, and it was found to be uniform throughout the ingot. In addition, the absorption peak maximum for the Cr 2+ ion in the Cr:CdS 0.8 Se 0.2 crystal is at 1.84 μm.

The new quaternary single crystals AgGaGe n Se 2( n +1) ( n = 1.5, 1.75, 2, 3, 4, 5, and 9) have high nonlinear optical property and can be used for mid-IR laser applications in high power. However, only AgGaGe 3 Se 8 and AgGaGe 5 Se 12 have been grown on a large scale and studied in detail. In this work, the AgGaGe n Se 2( n +1) ( n = 1.5, 1.75, 2, 3, 4, 5, and 9) crystals (Φ 20 mm × 40 mm and Φ 40 mm × 100 mm) were grown by the modified Bridgman method. The crystal structure was studied by X-ray diffraction and the Rietveld refinement method. The composition and morphology were characterized by scanning electron microscopy and metallurgical microscopy. The chemical state and vibration modes of surface elements were characterized by X-ray photoelectron spectroscopy and Raman spectra, and the electrical property was investigated by the Hall effect measurement, which indicates that all the single AgGaGe n Se 2( n +1) crystals are n-type semiconductors. The transmittance of all as-grown AgGaGe n Se 2( n +1) crystal wafers exceed 65% in the transparent range, and the band gap increases from 2.05 eV for AgGaGe 1.5 Se 5 to 2.14 eV for AgGaGe 9 Se 20 . Besides, after being annealed in two different conditions, the wafers show different changes. We discovered a special decomposition phenomenon during the annealing process and found the more appropriate annealing method at last. In addition, the absorption peaks at 4.2, 10, and 14.9 μm of wafers have been nearly eliminated, and the quality of most crystals has been improved.

Single-cell encapsulation is an emerging technology to endow cells with various functions, of which developing new applications in vivo is in high demand. Currently, metal-organic frameworks (MOFs) that are used as nanometric shells to coat living cells, however, have not realized cell-selective encapsulation. Here, a biocompatible and selective cell encapsulation strategy based on precursor-functionalized nucleolin aptamer and in situ MOF mineralization on the aptamer-identified cancer cell surface are developed. After MOF coating, the encapsulated cancer cells undergo immunogenic cell death, which is found associated with the changed cell stiffness (indicated by Young's modulus). The immunogenic dead cancer cells are used as whole-cell cancer vaccines (WCCVs), forming the integral WCCV-in-shell structure with enhanced immunogenicity ascribing from the surface-exposed calreticulin to promote dendritic cell recruitment, antigen presentation, and T-cell activation. The major activation pathways in the immune response are identified including tumor necrosis factor signaling pathway, cytokine-cytokine receptor interaction, and Toll-like receptor signaling pathway, suggesting the potential adjuvant effect of the MOF shells. After vaccination, WCCV-in-shell shows much better tumor immunoprophylaxis than either the imperfectly coated cancer cells or the traditional WCCV. This strategy is promising for the universal and facile development of novel whole-cell vaccines., (© 2022 Wiley-VCH GmbH.)

The preferable choice of sustained peptide delivery systems is generally polymer-based microspheres in which their large particle size, wide size distribution, low drug encapsulation efficacy, poor colloidal stability, and undesirable burst release eventually hinder their clinical translation. In this study, a nanoscale ternary Lixisenatide (Lix) sustained delivery system based on strong multivalent interactions (electrostatic and coordination complexation) among small molecular phytic acid (PA), Lix and Fe 3+ was developed. Flash nanocomplexation (FNC) was utilized to facilitate the rapid and efficient mixing of the three components and kinetically control the assembly process that enabled dynamic balance of two competitive chemical reactions with different kinetic rates (slow chemical reaction of PA/Lix and fast chemical reaction of PA/Fe 3+ ) to generate structural uniform ternary nanoparticles and avoid heterogeneous complexes. By tuning the mixing conditions (i.e., flow rate, mass ratio, concentration, pH value, etc.), the ternary PA/Lix/Fe 3+ nanoparticles were assembled with reproducible production in a manner of high uniformity and scalability, achieving small size (∼50 nm), uniform composition (PDI: ∼0.12), favourable colloidal stability, high encapsulation efficiency (∼100%), and tunable drug release kinetics. The optimized formulation exhibited a minor Lix release (<20%) in the first day and extended peptide release period over 8 days. Unexpectedly, upon a single injection administration, the as-prepared formulation (600 μg/kg) rapidly brought the high BGL (∼30 mmol/L) back to normal range (<10 mmol/L) within the initial 6 h and achieved a 180 h glycemic control in T2D mouse model. Moreover, this sustained peptide delivery system demonstrated a repeatable hypoglycemic effects and significantly suppressed the pathological damage of major organs following multiple injection. This sustained peptide delivery system with aqueous, facile and reproducible preparation process possesses good biocompatibility, tunable release kinetics, and prolonged hypoglycemic effects, portending its great translational potential in the chronic disease treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Improving health-related quality of life (HRQoL) and exercise capacity is an important goal of treatment in heart failure (HF). However, evidence for the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on the improvement of HRQoL and exercise capacity seems to be conflicted. We performed a systematic review and meta-analysis to evaluate the effects of SGLT-2 inhibitors on HRQL and exercise capacity in patients with heart failure and reduced ejection fraction (HFrEF)., Methods: All studies (up to March 20, 2021) evaluating the effects of SGLT-2 inhibitors on HRQoL and exercise capacity in patients with HFrEF were initially searched from four electronic search engines: PubMed, Web of Science, Cochrane Library, and SinoMed. All statistical analyses were performed with RevMan 5.4., Results: We included 9 articles describing 7 trials with 9428 patients. SGLT-2 inhibitors group exhibited significant improvement in HRQoL assessed by Kansas City Cardiomyopathy Questionnaires (KCCQ) (MD: 2.13, 95% CI: 1.11 to 3.14, p < 0.001) and the rate of KCCQ-overall summary score improvement≥5 points (RR 1.15, 95%CI 1.08 to 1.21, P < 0.001) compared with placebo. No significant difference was observed in exercise capacity assessed by 6-min walk test distance between SGLT-2 inhibitors and placebo (MD 24.45, 95%CI -22.82 to 71.72, P = 0.31)., Conclusions: Our meta-analysis demonstrates that SGLT-2 inhibitors significantly improve HRQoL, and supports the concept that SGLT-2 inhibitors do not significantly improve exercise capacity in patients with HFrEF. Studies with larger sample sizes and longer follow-up duration are needed to determine whether the treatment with SGLT-2 inhibitors may improve exercise ability., Prospero: CRD42021248346., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The rapid development of multidrug-resistant (MDR) bacteria due to the improper and overuse of antibiotics and the ineffective performance of antibiotics against the difficult-to-treat biofilm-related infections (BRIs) have urgently called for alternative antimicrobial agents and strategies in combating bacterial infections. Antimicrobial peptides (AMPs), owing to their compelling antimicrobial activity against MDR bacteria and BRIs without causing bacteria resistance, have attracted extensive attention in the research field. With the development of nanomaterial-based drug delivery strategies, AMPs-based nano-formulations have significantly improved the therapeutic effects of AMPs by ameliorating their hydrolytic stability, half-life in vivo, and solubility as well as reducing the cytotoxicity and hemolysis, etc. This review has comprehensively summarized the application AMPs-based nano-formulation in various bacterial infections models, including bloodstream infections (specifically sepsis), pulmonary infections, chronic wound infections, gastrointestinal infections, among others. The design of the nanomaterial-based drug delivery systems and the therapeutic effects of the AMPs-based nano-formulations in literature have been categorized and in details discussed. Overall, this review provides insights into the advantages and disadvantages of the current developed AMPs-based nano-formulations in literature for the treatment of bacterial infections, bringing inspirations and suggestions for their future design in the way towards clinical translation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The proliferation and differentiation of NSCs are regulated by miRNAs. This study investigated the role of miR-374a-5p in the proliferation and differentiation of ReNcell VM cells. ReNcell VM cells were transfected with miR-374a-5p mimic, miR-374a-5p inhibitor and Hes1, respectively. Cell proliferation was detected by clone formation assay. Target gene for miR-374a-5p was predicted by TargetScan and confirmed by dual-luciferase reporter. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to detect the expressions of relative genes. After culturing the cells in differentiation medium, the ReNcell VM cells differentiated into βIII-tubulin (Tuj1)-positive neurons and GFAP-positive astrocytes. The miR-374a-5p expression was increased as the cells continued to differentiate. Hes1, which was predicted to be the target gene for miR-374a-5p, was low-expressed during cell differentiation. The miR-374a-5p mimic decreased cell clones, inhibited the expressions of ki-67 and Nestin, but increased those of Tuj1 and GFAP. However, miR-374a-5p inhibitor produced the opposite effects to miR-374a-5p mimic. Hes1 increased the expressions of ki-67 and Nestin, but decreased those of Tuj1 and GFAP, moreover, Hes1 reversed the role of miR-374a-5p mimic. MiR-374a-5p inhibited the proliferation of Rencell VM cells and promoted the differentiation of NSCs by reducing the Hes1 expression., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

Acute kidney injury (AKI), a major health issue concerning ~50% of patients treated in intensive care units, generally leads to severe renal damage associated with high mortality rate. The application of nanotechnology for the management of AKI has profound potential of further development, providing innovative strategies for predicting the early onset and progression of renal disease and improving the treatment efficacy of the life-threating AKI. This review has comprehensively summarized the nanomedicines in the application of AKI diagnosis and emphatically discussed the unique potential of various nanotechnology-based drug delivery systems (e.g., polymeric nanoparticles, organic nanoparticles, inorganic nanoparticles, lipid-based nanoparticles, hydrogels etc.) in the treatment of AKI, allowing for improved therapeutic index by enhancing both efficacy and safety concurrently. These approaches may mechanically mitigate oxidative stress, inflammation, and mitochondrial and other organellar damage, etc. In addition, the combination of nanotechnology with stem cells-based therapy or gene therapy has been explored for reducing renal tissues damage and promoting kidney repair or recovery from AKI. The review provides insights into the synthesis, advantages, and limitations of innovative nanomedicine application in the early detection and effective treatment of AKI., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Quaternary nonlinear optical single crystals Ag x Ga x Ge 1- x Se 2 ( x = 0.250, 0.167) were grown by the Bridgman method in a four-zone furnace. The thermal expansion behavior of Ag x Ga x Ge 1- x Se 2 ( x = 0.25, 0.167) was studied by the method of single-crystal X-ray diffraction from 150 to 295 K and powder X-ray diffraction in the range of 298-773 K. Both results show the crystals have positive linear thermal expansion coefficients in different directions and a positive volume thermal expansion coefficient, and it is observed that they satisfy the relationship of α a > α c > α b and α V ≈ α a + α b + α c for the orthorhombic structure. It is found that the Ag x Ga x Ge 1- x Se 2 ( x = 0.25, 0.167) unit cells varying with temperature were mainly dominated by variations in framework geometry (AgSe 4 tetrahedron), and the thermal motion of Ag atoms in the AgSe 4 tetrahedron. As it was revealed, according to the powder X-ray diffraction, it is found that the isotropic thermal atomic displacement parameter of the Ag atoms is much larger than those of the Se and Ga(Ge) atoms in the AgSe 4 tetrahedron. Furthermore, anisotropic atomic displacement parameters (ADPs) of Ag atoms are extracted from the single-crystal diffraction; the ADPs along the a axis, b axis, and c axis have a significant difference, which means the thermal vibration of Ag atoms is anisotropic. It is of great significance for improving crystal growth technology and understanding the thermal properties of this kind of crystals.

Long non-coding RNA (lncRNA) is widely reported to be involved in cardiac (patho)physiology. Acute myocardial infarction, in which cardiomyocyte apoptosis plays an important role, is a life-threatening disease. Here, we report the lncRNA Chaer that is anti-apoptotic in cardiomyocytes during Acute myocardial infarction. Importantly, lncRNA Chaer is significantly downregulated in both oxygen-glucose deprivation (oxygen-glucose deprivation)-treated cardiomyocytes in vitro and AMI heart. In vitro , overexpression of lncRNA Chaer with adeno virus reduces cardiomyocyte apoptosis induced by OGD-treated while silencing of lncRNA Chaer increases cardiomyocyte apoptosis instead. In vivo , forced expression of lncRNA Chaer with AAV9 attenuates cardiac apoptosis, reduces infarction area and improves mice heart function in AMI. Interestingly, overexpression of lncRNA Chaer promotes the phosphorylation of AMPK, and AMPK inhibitor Compound C reverses the overexpression of lncRNA Chaer effect of reducing cardiomyocyte apoptosis under OGD-treatment. In summary, we identify the novel ability of lncRNA Chaer in regulating cardiomyocyte apoptosis by promoting phosphorylation of AMPK in AMI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 He, Zeng, Zhou, Liu, Han, Xu, Bu, Wang, Ke, Pan, Du, Xue, Lu and Luo.)

Background: Contemporary radiofrequency catheter ablation (RFCA) approaches for atrial fibrillation (AF) have reached an efficacy "ceiling". Ethanol infusion into the vein of Marshall (EI-VOM) has shown potential in preliminary studies. Data on EI-VOM are largely limited to small single-center reports, and clinical benefits and risks have not been systematically examined. Therefore, we performed a meta-analysis to assess the feasibility, efficacy, and safety of EI-VOM for AF., Methods: All studies evaluating EI-VOM for AF were initially searched from four electronic search engines: PubMed, Web of Science, Cochrane Library, and SinoMed. We used RevMan5.4 to calculate pooled outcomes of randomized controlled trial and cohort studies. We also performed single-arm meta-analyses using Open Meta-Analyst., Results: We included a total of 10 studies with 1322 patients. Successful EI-VOM was performed in 86.7% (95% CI 81.9-91.4%) of patients. For persistent AF patients, the recurrence of AF and/or atrial tachycardia (AT) was significantly lower in the EI-VOM combined with RFCA group compared with RFCA alone group (RR 0.58, 95% CI 0.35 to 0.96, p = 0.04). EI-VOM combined with RFCA significantly increased the rate of bidirectional mitral isthmus block compared with RFCA alone in AF patients (RR 1.50, 95% CI 1.34 to 1.67, p < 0.001). There were nine cardiac tamponades observed in 644 patients (PR 0.8%, 95% CI 0.1-1.5%) who were performed EI-VOM combined with RFCA., Conclusions: Our meta-analysis brings encouraging evidence that adjuvant EI-VOM reduces AF and/or AT recurrence rate in persistent AF patients and increases the success rate of bidirectional mitral isthmus block., (© 2021 Wiley Periodicals LLC.)

Self-assembly performed in ionic liquids (ILs) as a unique solvent promises distinct functions and applications in sensors, therapeutics, and optoelectronic devices due to the rich interactions between nanoparticle building blocks and ILs. However, the general consideration that common nanoparticles are readily destabilized by counterions in an IL has largely prevented researchers from investigating controlled nanoparticle assembly in IL-based systems. This study explores the assembling behaviour of double-stranded (ds) DNA-functionalized gold nanoparticles (dsDNA-AuNPs) in hydrated ionic liquids. The DNA base pair stacking assembly of dsDNA-AuNPs occurs at a low IL concentration (<5%). However, a moderate ionic liquid concentration (5-40%) can de-hybridize dsDNA and leaves single-stranded (ss) DNA stabilizing the AuNPs. In concentrated ionic liquids (>40%), interestingly, the higher ionic strength leads to the assembly of DNA-AuNPs. The triphasic assembly trend is also generally observed regardless of the type of IL. By down-regulation of DNA's melting temperature with the IL, the assembly of DNA-AuNPs affords robust response to a lower temperature range, promising applications in plasmonic devices and range-tunable temperature sensors.

Sepsis is a life threatening disease that is caused by a dysregulated host immune response to infection, resulting in tissue damage and organ dysfunction, which account for a high in-hospital mortality (approximately 20%). However, there are still no effective and specific therapeutics for clinical sepsis management. Nanomaterial-based strategies have emerged as promising tools for improving the therapeutic efficacy of sepsis by combating lethal bacterial infection, modulating systemic inflammatory response, preventing multiple organ failure, etc. This review has comprehensively summarized the recent advancements in nanomaterial-based strategies for the management of sepsis and severe complications, in which those nanosystems act either as inherent therapeutics or as nanocarriers for the precise delivery of agents. These formulations mechanically possess antibacterial, anti-inflammatory, immunomodulatory, and anti-oxidative effects, achieving multifunctional synergistic treatment efficacy against sepsis. Furthermore, several cell membrane-derived biomimetic nanoplatforms have been used as decoys to trap and neutralize the pathogenic toxins. The critical role of other adjuvant therapies in sepsis management, including the combination of nanotechnology and stem cell therapy, is also highlighted. Overall, this review provides insights into innovative nanotechnology-based strategies applied in sepsis treatment.

Peptide/protein therapeutics have been significantly applied in the clinical treatment of various diseases such as cancer, diabetes, etc . owing to their high biocompatibility, specificity, and therapeutic efficacy. However, due to their immunogenicity, instability stemming from its complex tertiary and quaternary structure, vulnerability to enzyme degradation, and rapid renal clearance, the clinical application of protein/peptide therapeutics is significantly confined. Though nanotechnology has been demonstrated to prevent enzyme degradation of the protein therapeutics and thus enhance the half-life, issues such as initial burst release and uncontrollable release kinetics are still unsolved. Moreover, the traditional administration method results in poor patient compliance, limiting the clinical application of protein/peptide therapeutics. Exploiting the sustained-release formulations for more controllable delivery of protein/peptide therapeutics to decrease the frequency of injection and enhance patient compliance is thus greatly meaningful. In this review, we comprehensively summarize the substantial advancements of protein/peptide sustained-release systems in the past decades. In addition, the advantages and disadvantages of all these sustained-release systems in clinical application together with their future challenges are also discussed in this review.

Second-harmonic generation (SHG) is a kind of nonlinear optical phenomenon which has been widely used in optical devices, and factors influencing its signal are very complex. Here, taking advantage of excellent structural designability and overcoming the limitations of various coordinations of lanthanide metals, for the first time a series of lanthanide metal-organic frameworks (Ln-MOFs) with one particular ligand were synthesized and structurally characterized to study the interference of the SHG signal. The optical performance including single-photon fluorescence and SHG was collected and analyzed. It is found that all 13 kinds of Ln-MOFs can be divided into 2 crystal configurations by their individual space groups and Ln-MOFs with coordinated metal atoms from La to Tb possessing the noncentrosymmetric C 2 space group exhibit the SHG property, the intensity of which depends on the type of metal atoms, the pumping wavelength, and the size of the single-crystal particles. This is the first time that the relationship between the nonlinear optical properties and the structure, metal atoms, pumping wavelength, crystal size of the whole series of Ln-MOFs is studied systematically, providing a lot of interesting results and enriching the research scope of nonlinear optics and materials science.

The sound velocities of water in the Hugoniot states are investigated by laser shock compression of precompressed water in a diamond anvil cell. The obtained sound velocities in the off-Hugoniot region of liquid water at precompressed conditions are used to test the predictions of quantum molecular dynamics (QMD) simulations and the SESAME equation-of-state (EOS) library. It is found that the prediction of QMD simulations agrees with the experimental data while the prediction of SESAME EOS library underestimates the sound velocities probably due to its improper accounting for the ionization processes.

Anisotropic gold nanoparticles have attracted great interest due to their unique physicochemical properties derived from the shape anisotropy. Manipulation of their interfacial interactions, and thereby the assembling behaviors are often requisite in their applications ranging from optical sensing and diagnosis to self-assembly. Recently, the control of interfacial force based on base pair stacking of DNA terminals have offered a new avenue to surface engineering of nanostructures. In this review, we focus on the DNA base stacking-induced assembly of anisotropic gold nanoparticles, such as nanorods and nanotriangles. The fundamental aspects of anisotropic gold nanoparticles are provided, including the mechanism of the anisotropic growth, the properties arising from the anisotropic shape, and the construction of DNA-grafted anisotropic gold nanoparticles. Then, the advanced applications of their functional assemblies in biosensing and ordered assembly are summarized, followed by a comparison with gold nanospheres. Finally, conclusions and the direction of outlooks are given including future challenges and opportunities in this field.

Diabetes mellitus (DM) is a metabolic disorder characterized by the presence of chronic hyperglycemia driven by insulin deficiency or resistance, imposing a significant global burden affecting 463 million people worldwide in 2019. This review has comprehensively summarized the application of nanomedicine with accurate, patient-friendly, real-time properties in the field of diabetes diagnosis and monitoring, and emphatically discussed the unique potential of various nanomedicine carriers (e.g., polymeric nanoparticles, liposomes, micelles, microparticles, microneedles, etc.) in the management of diabetes and complications. Novel delivery systems have been developed with improved pharmacokinetics and pharmacodynamics, excellent drug biodistribution, biocompatibility, and therapeutic efficacy, long-term action safety, as well as the improved production methods. Furthermore, the effective nanomedicine for the treatment of several major diabetic complications with significantly improved life qualities of diabetic patients were discussed in detail. Going through the literature review, several critical issues of the nanomedicine-based strategies applications need to be addressed such as stabilities and long-term safety effects in vivo, the deficiency of standard for formulation administration, feasibility of scale-up, etc. Overall, the review provides an insight into the design, advantages and limitations of novel nanomedicine application in the diagnostics, monitoring, and therapeutics of DM., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rationale: Cardiac fibrosis is observed in nearly every form of myocardial disease. Long non-coding RNAs (lncRNAs) have been shown to play an important role in cardiac fibrosis, but the detailed molecular mechanism remains unknown. Object: We aimed at characterizing lncRNA 554 expression in murine cardiac fibroblasts (CFs) after myocardial infarction (MI) to identify CF-enriched lncRNA and investigate its function and contribution to cardiac fibrosis and function. Methods and Results: In this study, we identified lncRNA NONMMUT022554 (lncRNA 554) as a regulator of MI-induced cardiac fibrosis. We found that lncRNA 554 was significantly up-regulated in the mouse hearts following MI. Further study showed that lncRNA 554 was predominantly expressed in cardiac fibroblasts, indicating a potential role of lncRNA 554 in cardiac fibrosis. In vitro knockdown of lncRNA 554 by siRNA suppressed fibroblasts migration and expression of extracellular matrix (ECM); while overexpression of lncRNA 554 promoted expression of ECM genes. Consistently, lentivirus mediated in vivo knockdown of lncRNA 554 could inhibit cardiac fibrosis and improve cardiac function in mouse model of MI. More importantly, TGF-β1 inhibitor (TEW-7197) could reverse the pro-fibrotic function of lncRNA 554 in CFs. This suggests that the effects of lncRNA 554 on cardiac fibrosis is TGF-β1 dependent. Conclusion: Collectively, our study illustrated the role of lncRNA 554 in cardiac fibrosis, suggested that lncRNA 554 might be a novel target for cardiac fibrosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Luo, He, Huang, Wang, Han, Xue, Liu, Zeng and Lu.)