Search

Background: Methimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is associated with high morbidity and mortality, requiring appropriate interventions. In this study, we compared adverse drug effects associated with MMI and PTU using a real‐world large pharmacovigilance database. Methods: We searched all Individual Case Safety Reports reported to be associated with MMI and PTU, from VigiBase between 1967 and June 2, 2021. We conducted disproportionality analysis (case/non‐case analysis) to analyze the difference in reported adverse drug reactions (ADRs) between antithyroid drugs (case) and the entire database (non‐cases). We further analyzed information for the cases of agranulocytosis and AAV. Results: Among 11 632 cases of ADRs reported after MMI intake, agranulocytosis occurred in 1633 cases and AAV occurred in 41 cases. For 5055 cases of ADRs reported after PTU intake, agranulocytosis occurred in 459 cases and AAV occurred in 110 cases. Agranulocytosis occurred after a median of 28 days after PTU intake and 33 days after MMI intake. More than 95% of the agranulocytosis cases were classified as serious, but most of them (65.1% for PTU and 70.4% for MMI) were reported to have recovered after dechallenge actions; mostly drug withdrawal. AAV occurred after a median of 668 days after PTU intake, and 1162 days after MMI intake. Conclusions: This is a pharmacoepidemiological study investigating agranulocytosis and AAV caused by MMI and PTU. Through this research, we could provide more specific insights into a safe prescription of antithyroid drugs in a real‐world setting. [ABSTRACT FROM AUTHOR]

This article presents the findings of a study on the efficacy of posaconazole prophylaxis in patients with aplastic anemia (AA) or hypoplastic myelodysplastic syndrome (hMDS) undergoing immunosuppressive therapy (IST). The study found that posaconazole was highly effective in preventing invasive fungal infections (IFI) during IST, with only one patient (5%) experiencing an IFI. The toxicity profile of posaconazole was manageable, and the drug was well-tolerated by patients. The study concludes that posaconazole prophylaxis is efficient and safe in this patient population, and further research is needed to validate these findings. [Extracted from the article]

Objective: AO/OTA 31‐A3.3 intertrochanteric fracture is the most unstable type of intertrochanteric fracture, with a high rate of postoperative complications and implant failure. We have designed a new intramedullary fixation, proximal femoral totally bionic nail (PFTBN), for the treatment of A3.3 intertrochanteric fracture. To test its biomechanical performance, we adopted the method of finite element analysis and compared PFTBN with proximal femoral nail antirotation (PFNA) and proximal femoral bionic nail (PFBN, another internal fixation we previously designed for stable intertrochanteric fractures). Methods: Mimics, 3‐matic, ANSYS, and other software were used to construct a highly precise and realistic 3D digital model of the human femur. An AO/OTA 31‐A3.3 intertrochanteric fracture of the femur was constructed according to the 2018 classification of AO/OTA, and then assembled with PFNA, PFBN and PFTBN models, respectively. The stress distribution and displacement distribution of the three groups of constructs were tested under three times the body weight load and one‐foot standing configuration. Results: In terms of maximum stress and maximum displacement, the PFTBN group outperforms the PFBN group, and the PFBN group, in turn, surpasses the PFNA group. The maximum stress of PFTBN group was 408.5 Mpa, that of PFBN group was 525.4 MPa, and that of PFNA group was 764.3 Mpa. Comparatively, the maximum stress in the PFTBN group was reduced by 46.6% when contrasted with the PFNA group. Moreover, the stress dispersion within the PFTBN group was more evenly distributed than PFNA group. Regarding maximum displacement, the PFTBN group displayed the least displacement at 5.15 mm, followed by the PFBN group at 7.32 mm, and the PFNA group at 7.73 mm. Notably, the maximum displacement of the PFTBN group was 33.4% less than that observed in the PFNA group. Additionally, the relative displacement between the fragment and implant at the tip of pressure screw or helical blade was 0.22 mm in the PFTBN group, 0.34 mm in the PFBN group, and substantially higher 0.51 mm in the PFNA group. Conclusion: The "lever‐reconstruction‐balance" theory provides a new perspective for us to understand the mechanical conduction of the proximal femur. Compared with PFNA, in treating A3.3 intertrochanteric fractures PFTBN can better reconstruct the function of lateral wall, restore physiological mechanical conduction, increase postoperative stability, and finally reduce the risk of postoperative cut‐out and implant failure. It might be a better alternative for the treatment of A3.3 intertrochanteric fracture. [ABSTRACT FROM AUTHOR]

Oregano (Origanum vulgare) seed is used as spices and is known to have anti‐inflammatory, antibacterial, and antioxidant effects. The anti‐fatty liver effects of oregano seed ethyl acetate (OSEA) were evaluated in high‐fat diet (HFD)‐induced obese mice. OSEA was orally administered with HFD for 10 weeks. The body weight, aspartate aminotransferase, alanine aminotransferase, cholesterol, triglyceride, and low‐density lipoprotein levels in the HFD with 100 mg/kg of OSEA significantly decreased by approximately 1.21‐, 1.44‐, 2.12‐, 1.12‐, 1.05, and 1.59 times, respectively, while high‐density lipoprotein levels increased by approximately 1.05 times compared to those in the HFD group (p <.05). In addition, the distribution of liver fat in the HFD with 100 mg/kg OSEA (OSEA 100) group decreased significantly (p <.05). Therefore, OSEA supplementation can ameliorate fatty liver disease and reduce the accumulation of triglycerides in adipose tissue. The expression of genes involved in liver fat accumulation, such as sterol regulatory element‐binding protein‐1c (Srebp‐1c), fatty acid synthase (Fas), stearoyl‐CoA desaturase‐1 (Scd1), and acetyl‐CoA carboxylase 1 (Acc1), significantly decreased in OSEA 100 by approximately 2.6‐, 1.74‐, 1.89‐, and 1.56‐times, respectively (p <.05). Therefore, OSEA may modify obesity and liver fat accumulation by regulating the expression of genes involved in lipid metabolism. [ABSTRACT FROM AUTHOR]

We present the first example of electrocatalytic three‐component annulation–iodosulfonylation of indole‐tethered 1,6‐enynes with arylsulfonyl hydrazides and KI for accessing various iodosulfonated pyrrolo[1,2‐a]indoles in moderate to excellent yields with high stereospecificity. This electrosynthesis opens new avenues for the construction of pyrrolo[1,2‐a]indoles skeleton with good functional group compatibility under environmentally benign condition. Based on the control experiments and cyclic voltammetry data, we suggested the plausible reaction mechanism which included anodic oxidation, homolysis of arylsulfonyl iodide, arylsulfonyl radical addition, 5‐exo‐dig cyclization, radical coupling or nucleophilic attack of iodide ions cascade. [ABSTRACT FROM AUTHOR]

Adipose‐derived stromal/stem cells (ASCs) have been extensively studied as cell sources for regenerative medicine for bone because of their excellent proliferative capacity and the ability to obtain a large number of cells with minimal donor morbidity. On the other hand, the differentiation potential of ASCs is generally lower than that of bone marrow‐derived stromal/stem cells and varies greatly depending on donors. In this study, we mined a marker that can predict the osteogenic potential of ASC clones and also investigated the usefulness of the molecule as the enhancer of osteogenic differentiation of ASCs as well as its mechanism of action. Through RNA‐seq gene analysis, we discovered that GSTT1 (Glutathione S‐transferase theta‐1) was the most distinguished gene marker between highly osteogenic and poorly osteogenic ASC clones. Knockdown of GSTT1 in high osteogenic ASCs by siGSTT1 treatment reduced mineralized matrix formation. On the other hand, GSTT1 overexpression by GSTT1 transfection or GSTT1 recombinant protein treatment enhanced osteogenic differentiation of low osteogenic ASCs. Metabolomic analysis confirmed significant changes of metabolites related to bone differentiation in ASCs transfected with GSTT1. A high total antioxidant capacity, low levels of cellular reactive oxygen species, and increased GSH/GSSG ratios were also detected in GSTT1‐transfected ASCs. When the in vivo effect of GSTT1‐transfected ASCs on bone regeneration was investigated with segmental long‐bone defect model in rats, bone regeneration was significantly better after implantation of GSTT1‐transfected ASCs compared with that of control vector‐transfected ASCs. In conclusion, GSTT1 can be a useful marker to screen the highly osteogenic ASC clones and also a therapeutic factor to enhance the osteogenic differentiation of poorly osteogenic ASC clones. © 2023 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Potential associations between the risk of neurodegenerative diseases and circulating levels of amino acids have been implied in both experimental research and observational studies. However, because of the confounding and reverse causality, the findings could be biased. We aimed to determine whether circulating amino acid levels have potential effects on the risk of neurodegenerative diseases through a more robust analysis. So, we performed a total of two MR analyses, a discovery two‐sample MR analysis, and a replication test, using summary‐level genome‐wide association study (GWAS) data, both with circulating levels of amino acids as exposure and risk of neurodegenerative diseases as an outcome. The potential causalities between nine amino acids (Glutamine [Glu], Leucine [Leu], Isoleucine [Ile], Phenylalanine [Phe], Valine [Val], Alanine [Ala], Tyrosine [Tyr], Histidine [His], and Glycine [Gly]) and six neurodegenerative disorders (Alzheimer's disease [AD], Parkinson's disease [PD], Multiple sclerosis [MS], Frontotemporal dementia [FTD], Lewy body dementia [DLB], Amyotrophic lateral sclerosis [ALS]) were explored in this study. According to the discovery MR analysis, 1 SD. increase in circulating levels of Gln was genetically determined to result in a 13% lower risk of AD (IVW ORSD [95% CI] = 0.872 [0.822, 0.926]; FDR = 7.46 × 10−5) while PD risk was decreased to 63% per SD. increase of circulating Leu levels (IVW ORSD [95% CI] = 0.628 [0.467, 0.843]; FDR = 0.021). Results from the replication test provide further evidence of the potential association between circulating Gln levels and AD risk (IVW ORSD [95% CI] = 0.094 [0.028, 0.311]; FDR = 9.98 × 10−4). Meanwhile, sensitivity analysis demonstrated that the significant relationships revealed by our two‐sample MR outcomes were reliable. Our analyses provided robust evidence of causal associations between circulating levels of Gln and AD risk as well as circulating Leu levels and risk of PD. However, the underlying mechanisms remain to be further investigated. [ABSTRACT FROM AUTHOR]

Within the intention-to-treat (ITT) population, nine patients completed six cycles of VAD, while eight, one and one patient each discontinued treatment due to disease progression, adverse events or death, respectively. Six of twelve patients with documented disease progression received subsequent anti-lymphoma treatment at the investigator's discretion. However, considering the incurable nature of MCL even with modern therapies,[6] the findings of BATMAN suggest that VAD may be a viable second- or later-line therapy for RRMCL. Despite recent advancements in frontline therapies, most mantle cell lymphoma (MCL) patients inevitably relapse.[1] Bruton's tyrosine kinase (BTK) inhibitors exhibit potent efficacy for relapsed or refractory MCL (RRMCL).[[2], [4]] However, these agents rarely cure the disease, requiring subsequent salvage treatments in many patients. [Extracted from the article]

Background: Necroptosis is a regulated inflammatory cell death which plays a significant role in cancer development and progression. In this study, we evaluated whether genetic variants in key regulators of necroptosis may affect survival outcome of non‐small cell lung cancer (NSCLC) patients after surgical resection. Methods: A total of 674 patients who underwent curative surgery were included. Fifteen genetic variants in key regulators of necroptosis (RIPK1, RIPK3, and MLKL) were selected. The association of these variants with survival outcomes was evaluated. Results: Two variants, RIPK1 rs17548629C > T and MLKL rs877375G > C, were associated with better overall survival and disease‐free survival in multivariate analyses. When the patients were divided according to histology, the associations were significant only in adenocarcinoma, but not in squamous cell carcinoma. RIPK1 rs17548629 C‐to‐T change was associated with significantly increased luciferase activity by modulating the binding of miR‐642a. Promoter assays showed a significantly increased promoter activity in MLKL rs877375C allele compared to G allele. Consistently, the mRNA expression level of RIPK1 and MLKL showed significant positive correlation with RIPK1 rs17548629C‐to‐T and MLKL rs877375G‐to‐C changes. Conclusion: Two genetic variants in key regulators in necroptosis, RIPK1 rs17548629C > T and MLKL rs877375G > C, may be used as biomarkers to predict survival outcomes in surgically resected NSCLC patients. [ABSTRACT FROM AUTHOR]

Organometal halide perovskites are promising semiconducting materials for photodetectors because of their favorable optoelectrical properties. Although nanoscale perovskite materials such as quantum dots (QDs) show novel behavior, they have intrinsic stability issues. In this study, an effectively silane barrier‐capped quantum dot (QD@APDEMS) is thinly applied onto a bulk perovskite photosensitive layer for use in photodetectors. QD@APDEMS is synthesized with a silane ligand with hydrophobic CH3‐terminal groups, resulting in excellent dispersibility and durability to enable effective coating. The introduction of the QD@APDEMS layer results in the formation of a low‐defect perovskite film with enlarged grains. This is attributed to the grain boundary interconnection effect via interaction between the functional groups of QD@APDEMS and uncoordinated Pb2+ in grain boundaries. By passivating the grain boundaries, where various trap sites are distributed, hole charge‐carrier injection and shunt leakage can be suppressed. Also, from the energy point of view, the deep highest occupied molecular orbital (HOMO) level of QD@APDEMS can work as a hole charge injection barrier. Improved charge dynamics (generation, transfer, and recombination properties) and reduced trap density of QD@APDEMS are demonstrated. When this perovskite film is used in a photodetector, the device performance (especially the detectivity) stands out among existing perovskites evaluated for energy sensing device applications. [ABSTRACT FROM AUTHOR]

Transition metal dichalcogenides (TMDCs) have attracted intense interest; however, despite the considerable effort of researchers, a universal manufacturing method that can guarantee both high material quality and throughput has not been realized to date. Herein, a universal approach to producing high‐quality monolayer TMDCs on a large scale via germanium (Ge)‐mediated atomic spalling is presented. Through the modified analytic model, the study verifies that the thin Ge film could be a suitable stressor that effectively reduces the crack propagation depth at the sub‐nanometer range. In particular, an acid‐etching process is not required in the overall atomic spalling process due to the water‐soluble nature of the Ge, enabling it widely applicable to various TMDCs. Under the optimized spalling conditions, a millimeter‐sized monolayer of stable MoS2, as well as unstable MoTe2, is successfully achieved. Through detailed spectroscopic and electrical characterizations, it is confirmed that the proposed methodology for obtaining large‐area atomic layers does not introduce any significant structural defects or chemical contaminations. [ABSTRACT FROM AUTHOR]

Background: Numerous nonsurgical but invasive cosmetic procedures are performed blindly in the dermis or subcutaneous fat layer of the facial skin. Objectives: To measure the numerical skin thickness of the facial areas where dermatological procedures are performed by applying ultrasound techniques, and to make it possible to estimate the skin thickness by investigating the influence of several individual constitutional factors such as age, sex, and body mass index (BMI), so that these variables can be applied to estimate skin thickness. Materials and methods: Skin thickness was measured at eight different facial points using an ultrasound machine (Affiniti 50; Philips Inc.). Demographic data were gathered using questionnaires. Manual BMI was calculated from the weight and height of each participant, and individual BMI measurements were performed using a body composition analyzer. Results: In terms of whole skin thickness, the thickest point was the mouth corner, and the thinnest point was the lateral forehead. The thickest point in the epidermis was the chin, and the thinnest point was the nasolabial fold. The thickest point in the dermis was the corner of the mouth, and the thinnest was the lateral forehead. Full skin thickness and dermal thickness were mostly lower in females. Skin thickness was not significantly correlated with BMI. Conclusion: The skin thickness at different points on the face was variable, and realistic data about skin thickness can be obtained by in vivo ultrasonographic analysis of the skin. [ABSTRACT FROM AUTHOR]

Cihunamides A–D (1–4), novel antibacterial RiPPs, were isolated from volcanic‐island‐derived Streptomyces sp. The structures of 1–4 were elucidated by 1H, 13C, and 15N NMR, MS, and chemical derivatization; they contain a tetrapeptide core composed of WNIW, cyclized by a unique C−N linkage between two Trp units. Genome mining of the producer strain revealed two biosynthetic genes encoding a cytochrome P450 enzyme and a precursor peptide. Heterologous co‐expression of the core genes demonstrated the biosynthesis of cihunamides through P450‐mediated oxidative Trp‐Trp cross‐linking. Further bioinformatic analysis uncovered 252 homologous gene clusters, including that of tryptorubins, which possess a distinct Trp‐Trp linkage. Cihunamides do not display the non‐canonical atropisomerism shown in tryptorubins, which are the founding members of the "atropitide" family. Therefore, we propose to use a new RiPP family name, "bitryptides", for cihunamides, tryptorubins, and their congeners, wherein the Trp‐Trp linkages define the structural class rather than non‐canonical atropisomerism. [ABSTRACT FROM AUTHOR]

The energy crisis and global shift toward sustainability drive the need for sustainable technologies that utilize often‐wasted forms of energy. A multipurpose lighting device with a simplistic design that does not need electricity sources or conversions can be one such futuristic device. This study investigates the novel concept of a powerless lighting device driven by stray magnetic fields induced by power infrastructure for obstruction warning light systems. The device consists of mechanoluminescence (ML) composites of a Kirigami‐shaped polydimethylsiloxane (PDMS) elastomer, ZnS:Cu particles, and a magneto–mechano‐vibration (MMV) cantilever beam. Finite element analysis and luminescence characterization of the Kirigami structured ML composites are discussed, including the stress–strain distribution map and comparisons between different Kirigami structures based on stretchability and ML characteristic trade‐offs. By coupling a Kirigami‐structured ML material and an MMV cantilever structure, a device that can generate visible light as luminescence from a magnetic field can be created. Significant factors that contribute to luminescence generation and intensity are identified and optimized. Furthermore, the feasibility of the device is demonstrated by placing it in a practical environment. This further proves the functionality of the device in harvesting weak magnetic fields into luminescence or light, without complicated electrical energy conversion steps. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of intimate partner violence (IPV) victimization and the factors associated with IPV during pregnancy and the early postnatal period in Korean community samples. Methods: We enrolled 5953 pregnant mothers and mothers with young children registered in the Early Life Health Management Program provided by 30 public health centers in Korea between 2020 and 2021. We used the Korean Hurt, Insult, Threaten, and Scream (K‐HITS) questionnaire to measure IPV. Sociodemographic, social support, and psychosocial variables were collected using self‐administered questionnaires. χ2 tests and multiple logistic regression analyses were conducted using SAS. Results: Using a cut‐off score of 6 with K‐HITS, the prevalence of IPV was 7.6%. According to multivariable logistic analyses, "have seen domestic violence during childhood or adolescence" (odds ratio [OR] 2.61, 95% confidence interval [CI] 1.95–3.50), unplanned pregnancy (OR 2.18, 95% CI 1.73–2.75), depression during pregnancy (OR 2.17, 95% CI 1.69–2.79), history of receiving treatment for emotional problems (OR 1.53, 95% CI 1.07–2.20), and living in a rural area (OR 1.52, 95% CI 1.01–2.29) increased the odds of IPV. "Having someone who talk to" was protective of IPV (for" "Not having someone to talk to": OR 2.24, 95% CI 1.49–3.35). Conclusions: Policies to prevent and address IPV during the perinatal period are urgently needed in Korea. Synopsis: This study provides the prevalence of and factors associated with intimate partner violence victimization among perinatal Korean women. [ABSTRACT FROM AUTHOR]

The growing need to process a diverse range of data has ignited effort in developing new multifunctional logic gate devices. In this article, we report a new form of all‐in‐one logic gate system that exploits the photoresponsivity of a self‐powered multifunctional BiFeO3 (BFO) sensor material. The BFO sensor can not only detect both light intensity and temperature, but it can also execute three common logic gates of "AND", "OR", and "NOT" by converting optical and thermal inputs into electrical output. The diverse functionality of the BFO logic gate sensor array utilizes the unique light‐and temperature‐controlled energy band structure and carrier behavior of the BFO material. To demonstrate the potential, a 3 × 3 logic gate sensor matrix is developed, which successfully detected light and temperature distributions, and accurately produced the three basic logic gate operations. This work provides a new route to construct highly integrated multifunctional electronic devices for the advancement of large sensing, communication, and computing operations. [ABSTRACT FROM AUTHOR]

Background: Despite therapeutic advances, lung cancer prognosis remains poor. Loss of heterozygosity (LOH) in the 3p21 region is well documented in lung cancer, but the specific causative genes have not been identified. Materials and Methods: Here, we aimed to examine the clinical impact of miR‐135a, located in the 3p21 region, in lung cancer. miR‐135a expression was assessed using quantitative real‐time polymerase chain reaction. LOH was analyzed at microsatellite loci D3S1076 and D3S1478, and promoter methylation status was determined by pyrosequencing of resected samples of primary non‐small‐cell lung cancer (NSCLC). The regulation of telomerase reverse transcriptase (TERT) was evaluated in lung cancer cells H1299 by luciferase report assays after treatment with miR‐135a mimics. Results: miR‐135a was significantly downregulated in squamous cell cancer (SCC) tumor tissues compared to normal tissues (p = 0.001). Low miR‐135a expression was more frequent in patients with SCC (p = 2.9 × 10−4) and smokers (p = 0.01). LOH and hypermethylation were detected in 27.8% (37/133) and 17.3% (23/133) of the tumors, respectively. Overall, 36.8% (49/133) of the NSCLC cases harbored either miR‐135a LOH or promoter hypermethylation. The frequencies of LOH and hypermethylation were significantly associated with SCCs (p = 2 × 10−4) and late‐stage (p = 0.04), respectively. MiR‐135a inhibited the relative luciferase activity of psiCHECK2‐TERT‐3'UTR. Conclusion: These results suggest that miR‐135a may act as a tumor suppressor to play an important role in lung cancer carcinogenesis, which will provide a new insight into the translational value of miR‐135a. Further large‐scale studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: Compared with total hip replacement, conventional collum femoris preserving prosthesis has a better bone retention effect. However, damage to the trabecular bone of the proximal femur leads to inevitable abnormal stress distribution, which leads to increased risks of femoral neck bone absorption, periprosthetic fracture, prosthesis loosening, rotation, and sinking. Thus, we compare the biomechanical properties of collum femoris preserving (CFP) and bionic collum femoris preserving (BCFP) hip prostheses. Methods: The Sawbone digital model (#3503, left, medium) was selected as the research object. We used the Mimics 21.0 software to reconstruct the digital model of the femur and the SolidWorks 2019 software to build and assemble the three‐dimensional models of CFP and BCFP prostheses. With the ANSYS Workbench 2021R1 software, the models were meshed and assigned values to simulate the load of a single foot under slow walking. We measured the mechanical distribution of the whole model and obtained the stress nephogram. Results: For CFP prosthesis, the peak stresses of the medial interface of the stem neck, the lateral interface of the stem neck, and the end of the stem were 64.894, 32.199, and 8.578 MPa, respectively; the peak stresses of the medial surface of the femoral shaft, the lateral surface of femoral shaft, the medial femoral neck bone‐prosthesis interface (osteotomy interface), the lateral femoral neck bone‐prosthesis interface (basal area), the lateral femoral neck bone‐prosthesis interface (osteotomy interface), and the greater trochanter area were 28.093, 24.790, 14.388, 5.118, 4.179, and 8.245 MPa, respectively; the valley stress of the greater trochanter area was 1.134 MPa. For BCFP prosthesis, the peak stresses of the medial interface of the stem neck, the lateral interface of the stem neck, and the end of the stem were 47.015, 26.771, and 47.593 MPa, respectively; the peak stress of tension screw was 15.739 MPa; the peak stresses of the medial surface of the femoral shaft, the lateral surface of femoral shaft, the medial femoral neck bone‐prosthesis interface (osteotomy interface), the lateral femoral neck bone‐prosthesis interface (basal area), the lateral femoral neck bone‐prosthesis interface (osteotomy interface) and the greater trochanter area were 28.581, 25.364, 15.624, 6.434, 4.986, and 8.796 MPa, respectively; the valley stress of the greater trochanter area was 1.419 MPa; the peak stress of bone‐metal interface between the tension screw and the lateral surface of the femur was 5.858 MPa. Conclusion: Compared with the CFP prosthesis, the design of the BCFP prosthesis is based on the lever balance theory. With the bionic reconstruction of tension trabeculae, BCFP prosthesis makes up for the defects of CFP prosthesis design, optimizes the stress distribution, and reduces the stress shelter effect of the proximal femur, which has better biomechanical properties. [ABSTRACT FROM AUTHOR]

Broadband terahertz (THz) chirality and wavefront manipulation play important roles in wireless communication, imaging, and radar systems. In this work, by integrating liquid crystal (LC) into a dielectric metasurface, the gradient phase distribution from the Si metasurface and the tunable birefringent phase shift from LC are engineered to perform an active spin‐decoupled beam steering with the strong spin asymmetric transmission. By using geometric symmetry analysis, the relationships between the symmetry breaking and the optical chirality of the metadevice are revealed under different LC orientations, and both the simulations and experiments further verify the dependence of this chirality on spin‐decoupled beam steering with different spin states. The results show that with the orientation changes of the LC by driving the different magnetic fields, the circular dichroism of the device at the 0° deflection angle is ≈100% dynamically modulated and even flipped in the broadband range of 0.8–1.3 THz. With these changes in THz chirality, a tunable spin‐decoupled beam steering occurs in the range of 25°‐45°. This work shows that tunable LC anisotropy leads to more complex symmetry breaking in this structure, and results in more functions than conventional spin‐decoupled wavefront manipulations, which expands the scope of THz chiral metadevice and its applications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ionotropic γ‐aminobutyric acid (GABA) receptor (GABAR) in an insect is the major inhibitory receptor and is one of the most important targets for insecticides. Due to the high spatiotemporal resolution of GABAR, the photopharmacological ligands acting on it in vertebrates but not insect have been developed. RESULTS: In this study, two types of photochromic ligands (PCLs) including DTFIPs (DTFIP1 and DTFIP2) and ABFIPs (p‐, m‐, and o‐ABFIP) were synthesized by incorporating photoswitch azobenzene or dithienylethene into fipronil (FIP), which is the antagonist of insect GABAR. Their photomodulation was measured by mosquito larval behavior, and their potential action mechanism was explored by the two‐electrode voltage clamp (TEVC) technique in vitro. DTFIP1 and m‐ABFIP exhibited the most significant difference of insecticidal activity by about 90‐ and 5‐fold to mosquito larvae between non‐irradiated and irradiated formation, respectively, and allowed for optical control of mosquito swimming activity. TEVC assay results indicated that m‐ABFIP and DTFIP1 enable optical control over the homomeric LsRDL‐type GABAR, which is achieved by regulating the chloride channel of resistance to dieldrin (RDL)‐type GABAR by photoisomerization. CONCLUSION: Our results suggested that PCLs synthesized from fipronil provide an alternative and precise tool for studying insect ionotropic GABARs and GABA‐dependent behavior. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of oral administration of magnesium‐L‐threonate, a novel magnesium compound, on the analgesic effect of opioids in patients with advanced cancer. Methods: We performed a prospective, randomized, double‐blind trial at a tertiary hospital in Shanghai, China. Eligible cancer patients who took opioids orally were assigned randomly to receive L‐TAMS capsules (1.5 g or 2.0 g according to weight) or a placebo (starch capsules). The primary outcome was the increase in the daily oral dose of morphine in each of the two groups, measured at 7, 14, 21, 30, 60, and 90 days during this trial. Results: A total of 116 patients from the oncology and pain departments, including inpatients and outpatients, were screened; 83 were enrolled. The increases in daily morphine doses began to differ from day 30 (L‐TAMS group 9.85 mg/d vs. Placebo group 20.49 mg/d, p < 0.05); the differences persisted on day 60 (L‐TAMS group 15.96 mg/d vs. Placebo group 29.06 mg/d, p < 0.05) and on day 90 (L‐TAMS group 21.20 mg/d vs. Placebo group 40.44 mg/d, p < 0.01). Conclusions: L‐TAMS outperforms a placebo in enhancing the analgesic effect of opioids and reducing the necessary opioid dosage. Moreover, L‐TAMS can significantly relieve opioid‐induced constipation. These advantages may be beneficial to patients with advanced cancer. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a highly metastatic and invasive malignant tumor that originates in the nasopharynx. The DNA‐binding protein WD repeat and HMG‐box DNA‐binding protein 1 (WDHD1) are highly expressed in a variety of tumours, but its expression and mechanism of action in NPC have not been reported to date. To investigate the involvement of WDHD1 in NPC, we first mined databases for the gene expression profile of NPC. Immunohistochemistry (IHC) was performed on 338 cases of NPC and 112 non‐NPC samples to verify the results. We report that the expression of WDHD1 is significantly elevated in NPC. ChIP‐seq was used to show that integrin alpha V (ITGAV) and WDHD1 exhibit a significant binding peak in the promoter region of the ITGAV gene. The expression levels of ITGAV and WDHD1 exhibit a significant positive correlation, and IHC was performed to show that ITGAV is highly expressed in NPC. Expression of ITGAV increased after overexpression of WDHD1, suggesting that ITGAV may be a potential target gene of WDHD1. Pathway analysis showed that both genes were closely related to the cell cycle, and flow cytometry was used to further confirm that decreased expression of WDHD1 significantly increased the number of apoptotic cells. In conclusion, our results suggest that expression of WDHD1 is increased in NPC and is likely to be associated with the NPC cell cycle; thus, we propose that WDHD1 may have the potential as a target gene for primary screening and treatment of NPC. [ABSTRACT FROM AUTHOR]

Background: Preclinical data have shown the immunomodulatory effects of metformin and dipeptidyl peptidase 4 (DPP4) inhibitors in patients with diabetes. However, its clinical impact remains unclear in lung cancer. Methods: Between 2017 and 2021, 466 patients received ICI monotherapy. Patients were categorized into concurrent (MET; metformin or combination of metformin and DPP4 inhibitor) and without concomitant (NMET; nonmetformin/DPP4 inhibitors) administration of metformin and DPP4 inhibitors groups at least 8 weeks before and during ICI therapy. The primary objectives were the objective response rate (ORR) and progression‐free survival (PFS). The second objective was to evaluate the overall survival (OS) and the occurrence of immune‐related adverse events (irAEs). Results: Among 466 patients, 89 (19.0%) and 377 (81%) were categorized into the MET and NMET groups, respectively. MET group had a significantly higher ORR (MET group: 24.7% vs. NMET group: 14.8%, p = 0.025) and longer PFS than those in the NMET group (MET group 5.1 month vs. NMET group 2.8 months, p = 0.018). After patients were stratified based on the prior line of therapy and PD L1 expression status, the PFS of the second‐line therapy and PD L1 ≥50 was significantly higher in the MET than in the NMET group. The proportion of patients experiencing all‐grade irAEs was numerically higher in the MET group (19.1%) than in the NMET group (14.3%), without statistical significance (p = 0.382). Conclusions: Concurrent use of metformin and DPP4 inhibitors with ICIs significantly improved the clinical outcomes without increasing the incidence of irAEs in NSCLC. [ABSTRACT FROM AUTHOR]

Summary: Rice production is threatened by multiple pathogens. Breeding cultivars with broad‐spectrum disease resistance is necessary to maintain and improve crop production. Previously we found that overexpression of miR160a enhanced rice blast disease resistance. However, it is unclear whether miR160a also regulates resistance against other pathogens, and what the downstream signaling pathways are.Here, we demonstrate that miR160a positively regulates broad‐spectrum resistance against the causative agents of blast, leaf blight and sheath blight in rice. Mutations of miR160a‐targeted Auxin Response Factors result in different alteration of resistance conferred by miR160a. miR160a enhances disease resistance partially by suppressing ARF8, as mutation of ARF8 in MIM160 background partially restores the compromised resistance resulting from MIM160.ARF8 protein binds directly to the promoter and suppresses the expression of WRKY45, which acts as a positive regulator of rice immunity. Mutation of WRKY45 compromises the enhanced blast resistance and bacterial leaf blight resistance conferred by arf8 mutant.Overall, our results reveal that a microRNA coordinates rice broad‐spectrum disease resistance by suppressing multiple target genes that play different roles in disease resistance, and uncover a new regulatory pathway mediated by the miR160a‐ARF8 module. These findings provide new resources to potentially improve disease resistance for breeding in rice. [ABSTRACT FROM AUTHOR]

Although the Trithorax histone methyltransferases ATX1–5 are known to regulate development and stress responses by catalyzing histone H3K4 methylation in Arabidopsis thaliana, it is unknown whether and how these histone methyltransferases affect DNA methylation. Here, we found that the redundant ATX1–5 proteins are not only required for plant development and viability but also for the regulation of DNA methylation. The expression and H3K4me3 levels of both RNA‐directed DNA methylation (RdDM) genes (NRPE1, DCL3, IDN2, and IDP2) and active DNA demethylation genes (ROS1, DML2, and DML3) were downregulated in the atx1/2/4/5 mutant. Consistent with the facts that the active DNA demethylation pathway mediates DNA demethylation mainly at CG and CHG sites, and that the RdDM pathway mediates DNA methylation mainly at CHH sites, whole‐genome DNA methylation analyses showed that hyper‐CG and CHG DMRs in atx1/2/4/5 significantly overlapped with those in the DNA demethylation pathway mutant ros1 dml2 dml3 (rdd), and that hypo‐CHH DMRs in atx1/2/4/5 significantly overlapped with those in the RdDM mutant nrpe1, suggesting that the ATX paralogues function redundantly to regulate DNA methylation by promoting H3K4me3 levels and expression levels of both RdDM genes and active DNA demethylation genes. Given that the ATX proteins function as catalytic subunits of COMPASS histone methyltransferase complexes, we also demonstrated that the COMPASS complex components function as a whole to regulate DNA methylation. This study reveals a previously uncharacterized mechanism underlying the regulation of DNA methylation. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the relationship between genetic variants in LKB1/AMPK/mTOR pathway and treatment outcomes of patients with non‐small cell lung cancer (NSCLC) treated with chemotherapy. A total of 379 patients with NSCLC who underwent first‐line paclitaxel‐cisplatin chemotherapy was enrolled. The associations between 19 single nucleotide variants (SNVs) in the LKB1/AMPK/mTOR pathway and the chemotherapy response and overall survival (OS) were analyzed. Among the SNVs analyzed, AKT1 rs2494750G>C and TSC1 rs2809244C>A were associated with clinical outcomes after chemotherapy in multivariate analyses. The AKT1 rs2494750G>C was significantly associated with a better response to chemotherapy (adjusted odds ratio [aOR]: 1.92, 95% confidence interval [CI]: 1.02–3.62, p = 0.04). The TSC1 rs2809244C>A were significantly associated with better OS (adjusted hazard ratio [aHR]: 0.79, 95% CI: 0.62–0.99, p = 0.04). When stratified by tumor histology, AKT1 rs2494750G>C exhibited a significant association with the chemotherapy response only in adenocarcinoma and TSC1 rs2809244C>A was also significantly associated with OS only in adenocarcinoma. This result suggests that the AKT1 rs2494750G>C and TSC1 rs2809244 C>A may be useful for predicting the clinical outcome of first‐line paclitaxel‐cisplatin chemotherapy in NSCLC. [ABSTRACT FROM AUTHOR]

Aim: We investigated the association of food allergy, food sensitisation, and food restriction with growth and micronutrients levels in schoolchildren. Methods: A total of 195 schoolchildren (6–12 years old) from six elementary schools in Korea were enrolled, and questionnaires were administered to their parents during June and July 2015. Food allergy was defined by the presence of urticaria, skin rash, pruritus, throat tightness, gastrointestinal complaints, or respiratory difficulty after consumption of a food to which allergy was plausible during the past 12 months. Skin prick tests were performed and serum levels of haemoglobin and micronutrients were measured. Results: Among 195 participants (51.3% males) enrolled, 35 (17.9%) were reported to have food allergies, 17 (8.7%) were on food restriction, and 27 (14.0%) were sensitised to at least one food allergen. Food allergy and food restriction were associated with a lower height-for- age z-score (p for trend = 0.018, p = 0.048; p for trend = 0.076, p = 0.008). Food restriction was related to reduced serum calcium level (aOR: −0.094, 95% CI: −0.156 to −0.032). Conclusion: Signs and symptoms of food allergy and consequent food restrictions in children were related to lower height-for- age z-score and lower serum calcium levels. [ABSTRACT FROM AUTHOR]

Since large cell acanthoma (LCA) has many overlapping clinical and histopathological features with other epidermal pigmented tumours, an additional method to differentiate it would be of great clinical significance. A retrospective study was performed on 33 lesions (26 patients) to identify distinct dermoscopic findings of LCA and to describe dermoscopic‐histopathological correlations. The results revealed that dermoscopy significantly aids in the distinction of LCA from other epidermal tumours included in the differential diagnosis. Yellow opaque homogeneous background, brown dots, and moth‐eaten border are common findings, and prominent skin markings and short white streaks are additional distinguishing features. Several important findings that are common in other diseases are rare in LCA. [ABSTRACT FROM AUTHOR]

Genital keratotic lesions include bowenoid papulosis (BP), which histologically resembles squamous cell carcinoma in situ containing high‐risk HPV, condyloma acuminatum (CA) that is a genital wart containing mostly low‐risk HPV, and genital seborrheic keratosis (GSK), which is a benign epidermal tumour lacking a clear etiologic relationship with HPV. This study compared HPV genotype distributions among BP, CA and GSK and revealed that BP and GSK were related to high‐risk HPV whereas CA was related to low‐risk HPV. It is plausible that GSK is a distinct epidermal tumour often related to high‐risk HPV rather than merely a senescent form of CA considering the overall discrepancy in the frequency distribution of HPV genotypes along with histopathological differences, and the detection of high‐risk HPV in GSK alerts physicians to consider more active treatment and continued follow‐ups. [ABSTRACT FROM AUTHOR]

Poor survival of grafted cells is the major impediment of successful cell‐based therapies for bone regeneration. Implanted cells undergo rapid death in an ischemic environment largely because of hypoxia and metabolic stress from glucose deficiency. Understanding the intracellular metabolic processes and finding genes that can improve cell survival in these inhospitable conditions are necessary to enhance the success of cell therapies. Thus, the purpose of this study was to investigate changes of metabolic profile in glucose‐deprived human bone marrow stromal/stem cells (hBMSCs) through metabolomics analysis and discover genes that could promote cell survival and osteogenic differentiation in a glucose‐deprived microenvironment. Metabolomics analysis was performed to determine metabolic changes in a glucose stress metabolic model. In the absence of glucose, expression levels of all metabolites involved in glycolysis were significantly decreased than those in a glucose‐supplemented state. In glucose‐deprived osteogenic differentiation, reliance on tricarboxylic acid cycle (TCA)‐predicted oxidative phosphorylation instead of glycolysis as the main mechanism for energy production in osteogenic induction. By comparing differentially expressed genes between glucose‐deprived and glucose‐supplemented hBMSCs, NR2F1 (Nuclear Receptor Subfamily 2 Group F Member 1) gene was discovered to be associated with enhanced survival and osteogenic differentiation in cells under metabolic stress. Small, interfering RNA (siRNA) for NR2F1 reduced cell viability and osteogenic differentiation of hBMSCs under glucose‐supplemented conditions whereas NR2F1 overexpression enhanced osteogenic differentiation and cell survival of hBMSCs in glucose‐deprived osteogenic conditions via the protein kinase B (AKT)/extracellular signal‐regulated kinase (ERK) pathway. NR2F1‐transfected hBMSCs significantly enhanced new bone formation in a critical size long‐bone defect of rats compared with control vector‐transfected hBMSCs. In conclusion, the results of this study provide an understanding of the metabolic profile of implanted cells in an ischemic microenvironment and demonstrate that NR2F1 treatment may overcome this deprivation by enhancing AKT and ERK regulation. These findings can be utilized in regenerative medicine for bone regeneration. © 2022 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Ferroelectric materials have been a focus of much research over the last few decades for their unique piezoelectric and optoelectronic properties. Conventional solar cells have been devised based on the photovoltaic effect of semiconductor p–n junctions, with their photogenerated voltage being influenced by the bandgap of the semiconductors, limiting their further development. Ferroelectric photovoltaics have attracted attention for their unusual photovoltaic effect and controllability. The photogenerated voltage that is independent of bandgap along the polarization direction can be generated in ferroelectric materials, undoubtedly making up for the lack of solar cells. Ferroelectric materials have been used in a wide range of piezoelectric, storage, sensor, and optoelectronic because of their unique optical and electrical properties. However, the small photogenerated current of ferroelectric photovoltaic devices is one of the challenges that need to be overcome. Researchers have shown that the photogenerated current of ferroelectric photovoltaic devices can be significantly improved by cation doping and heterostructure construction, reigniting the enthusiasm for the investigation of ferroelectric photovoltaics. This paper reviews a variety of ferroelectric photovoltaic materials, the mechanism of ferroelectric photovoltaics, approaches for improving ferroelectric photovoltaic performance, and the applications and future prospects for ferroelectric materials. [ABSTRACT FROM AUTHOR]

SUMMARY Many rice microRNAs have been identified as fine‐tuning factors in the regulation of agronomic traits and immunity. Among them, Osa‐miR535 targets SQUAMOSA promoter binding protein‐like 14 (OsSPL14) to positively regulate tillers but negatively regulate yield and immunity. Here, we uncovered that Osa‐miR535 targets another SPL gene, OsSPL4, to suppress rice immunity against Magnaporthe oryzae. Overexpression of Osa‐miR535 significantly decreased the accumulation of the fusion protein SPL4TBS‐YFP that contains the target site of Osa‐miR535 in OsSPL4. Consistently, Osa‐miR535 mediated the cleavage of OsSPL4 mRNA between the 10th and 11th base pair of the predicted binding site at the 3′ untranslated region. Transgenic rice lines overexpressing OsSPL4 (OXSPL4) displayed enhanced blast disease resistance accompanied by enhanced immune responses, including increased expression of defense‐relative genes and up‐accumulated H2O2. By contrast, the knockout mutant osspl4 exhibited susceptibility. Moreover, OsSPL4 binds to the promoter of GH3.2, an indole‐3‐acetic acid‐amido synthetase, and promotes its expression. Together, these data indicate that Os‐miR535 targets OsSPL4 and OsSPL4‐GH3.2, which may parallel the OsSPL14‐WRKY45 module in rice blast disease resistance. Significance Statement: Previously, Osa‐miR535 was identified to target SPL14 to regulate rice immunity. Here, we identified that Osa‐miR535 targets another SPL family gene, OsSPL4. OsSPL4 binds the promoter of GH3.2 to positively regulate rice immunity, which functionally parallels with OsSPL14‐WRKY45 module downstream of Osa‐miR535. [ABSTRACT FROM AUTHOR]

Summary: MicroRNAs (miRNAs) play vital roles in plant development and defence responses against various stresses. Here, we show that blocking miR1871 improves rice resistance against Magnaporthe oryzae and enhances grain yield simultaneously. The transgenic lines overexpressing miR1871 (OX1871) exhibit compromised resistance, suppressed defence responses and reduced panicle number resulting in slightly decreased yield. In contrast, the transgenic lines blocking miR1871 (MIM1871) show improved resistance, enhanced defence responses and significantly increased panicle number leading to enhanced yield per plant. The RNA‐seq assay and defence response assays reveal that blocking miR1871 resulted in the enhancement of PAMP‐triggered immunity (PTI). Intriguingly, miR1871 suppresses the expression of LOC_Os06g22850, which encodes a microfibrillar‐associated protein (MFAP1) locating nearby the cell wall and positively regulating PTI responses. The mutants of MFAP1 resemble the phenotype of OX1871. Conversely, the transgenic lines overexpressing MFAP1 (OXMFAP1) or overexpressing both MFAP1 and miR1871 (OXMFAP1/OX1871) resemble the resistance of MIM1871. The time‐course experiment data reveal that the expression of miR1871 and MFAP1 in rice leaves, panicles and basal internode is dynamic during the whole growth period to manipulate the resistance and yield traits. Our results suggest that miR1871 regulates rice yield and immunity via MFAP1, and the miR8171‐MFAP1 module could be used in rice breeding to improve both immunity and yield. [ABSTRACT FROM AUTHOR]

In this paper, we report the synthesis and characterization of composites of bioplastics (Poly‐lactic Acid (PLA), Polyhydroxyalkaonate (PHA), and PLA‐PHA blends) filled with dried grains with solubles (DDGS) and hydroxyapatite (HAP) by using a solvent casting process. Detailed microstructural, thermal, and mechanical characterization is presented in the text. At low concentrations of HAP (5–10 vol%) and DDGS (5–31 vol%) additions, the bioplastic films had mechanical integrity, but the ultimate tensile strength (UTS) decreased after the addition of DDGS and HAP reinforcements due to poor adhesion between the bioplastics and fillers. In the intermediate concentration, pre‐pregnated chips of DDGS (31–51 vol%)‐bioplastics and HAP (30–50 vol%)‐bioplastics with dichloromethane (DCM) were partially dried and then hot‐pressed to produce bulk samples (HPC‐process). The addition of bioplastics improved the plasticity of DDGS‐bioplastics composites. The HAP‐bioplastics composites showed polymer dependent response, for example the ultimate compressive strength (UCS) of 50%HAP‐PLA, and 30%HAP‐PLA were 77.6 ± 10.2 and 97.7 ± 5.9 MPa, respectively which are comparable to bone. The DDGS additions increased the hydrophilicity of PLA, PHA, and PLA‐PHA blend. For comparison, HAP increased the hydrophilicity of PHA and PLA‐PHA blends. At higher concentration (bioplastics with 70 vol% HAP additions), the films converted into microencapsulated HAP particles with bioplastics by a simple milling process thus eliminating the need for emulsions and/or surfactants during the microencapsulation process. [ABSTRACT FROM AUTHOR]

Adenosine triphosphate‐dependent chromatin remodeling complexes are important for the regulation of transcription, DNA replication, and genome stability in eukaryotes. Although genetic studies have illustrated various biological functions of core and accessory subunits of chromatin‐remodeling complexes in plants, the identification and characterization of chromatin‐remodeling complexes in plants is lagging behind that in yeast and animals. Recent studies determined whether and how the Arabidopsis SWI/SNF, ISWI, INO80, SWR1, and CHD chromatin remodelers function in multi‐subunit complexes in Arabidopsis. Both conserved and plant‐specific subunits of chromatin‐remodeling complexes have been identified and characterized. These findings provide a basis for further studies of the molecular mechanisms by which the chromatin‐remodeling complexes function in plants. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin A can be used to eliminate dynamic wrinkles by relaxing the muscles involved in facial expressions. Therefore, it is essential to know the location, origin, insertion, function, and changes of the facial expression muscles according to their contraction. Methods: After drawing the muscles on the face of a model, pictures were taken at rest. The model was then asked to make facial expressions that cause facial wrinkles. All images were taken with the Vectra H1 camera system (Canfield Scientific, Inc., Fairfield, New Jersey). Each expression image was aligned to its respective static image to compute the differences in skin position, so as to calculate the skin displacement vectors. The values for local changes in skin displacement were calculated by applying the automated algorithms of the Vectra Software Mirror Suite and visualized using the color and size of the arrow. Results: Face painting and 3D skin vector displacement analyses enabled visualization of all the facial muscles involved in facial expressions working dynamically, allowing us to visualize the effect of each muscle in the creation of hyperkinetic wrinkles. Face painting and 3D skin vector displacement analyses can be combined to determine the location of the wrinkles, extent of the muscle, part of the muscle that contracts, presence of asymmetry, direction in which the muscle contracts, and correlation between the antagonists and synergistic muscles. Conclusion: The botulinum toxin A injection educational model using body painting and 3D skin vector displacement analyses can provide a deeper understanding of actual moving muscle anatomy. Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

The current study evaluated the hypothesis that the administration of spheroidal adipose‐derived stromal/stem cells (ASCs) promotes cell survival and arrests the progression of surgically induced osteoarthritis (OA) in a rat model. We also tested the optimal conditions for spheroid production from ASCs using microwell methods. The formation of ASC spheroids was optimized at a well diameter of 600 μm under cell concentrations of 106cell/ml. When ASC spheroids cultured in 3D were compared with ASCs cultured in 2D monolayer, the cell survival and chondrogenic potential were enhanced while the apoptosis was reduced in ASC spheroids compared with ASCs in 2D monolayer culture. In vivo tracking of fluorescently labeled ASCs in the knee joints of rats with surgically induced OA showed longer fluorescent activity at a higher intensity in ASC spheroids than in ASC single‐cell suspension. When OA‐induced rats treated with ASC injection were sacrificed after 8 weeks, the OARSI score was enhanced in both ASC single‐cell suspension and ASC spheroids compared with negative control, spheroid treatment resulting in a better score than single‐cell treatment. However, injected cells were not detectable from the joints. These finding altogether suggests that ASC spheroids have better in vitro and in vivo survival and chondrogenic potential and exert greater regenerative effects for articular cartilage and arrest the progression of surgically induced OA better than ASCs in single‐cell suspension by the paracrine mode of action. The study findings support the notion of developing cell therapeutics to treat OA based on ASC spheroid forms. [ABSTRACT FROM AUTHOR]

Chinese mahogany (Toona sinensis) is a woody plant that is widely cultivated in China and Malaysia. Toona sinensis is important economically, including as a nutritious food source, as material for traditional Chinese medicine and as a high‐quality hardwood. However, the absence of a reference genome has hindered in‐depth molecular and evolutionary studies of this plant. In this study, we report a high‐quality T. sinensis genome assembly, with scaffolds anchored to 28 chromosomes and a total assembled length of 596 Mb (contig N50 = 1.5 Mb and scaffold N50 = 21.5 Mb). A total of 34,345 genes were predicted in the genome after homology‐based and de novo annotation analyses. Evolutionary analysis showed that the genomes of T. sinensis and Populus trichocarpa diverged ~99.1–103.1 million years ago, and the T. sinensis genome underwent a recent genome‐wide duplication event at ~7.8 million years and one more ancient whole genome duplication event at ~71.5 million years. These results provide a high‐quality chromosome‐level reference genome for T. sinensis and confirm its evolutionary position at the genomic level. Such information will offer genomic resources to study the molecular mechanism of terpenoid biosynthesis and the formation of flavour compounds, which will further facilitate its molecular breeding. As the first chromosome‐level genome assembled in the family Meliaceae, it will provide unique insights into the evolution of members of the Meliaceae. [ABSTRACT FROM AUTHOR]

Multifunctional sensors that can simultaneously detect light and thermal stimuli play an essential role in the research of portable devices and complex arrays of electronics. Lots of effort has been made to realize the simultaneous detection of light and temperature in a standalone device. However, since there is a strong interference of electric signals, accurate simultaneous sensing remains a challenge. Here, a self‐powered dual‐parameter sensor based on thermo‐phototronic effect in Nb‐doped SrTiO3 (NSTO) single crystal to achieve decoupled light and temperature sensing is developed. High light‐ and temperature‐sensing sensitivities of 0.201 µA mW cm−2 and 16.77 µA K−1 are realized, respectively. The excellent simultaneous sensing capability may be attributed to effective light‐to‐electrical and thermal‐to‐electrical energy conversion in the NSTO crystal. The excellent simultaneous sensing performance of the dual‐parameter sensors, together with their ease of fabrication, pushes forward the development of highly sensitive multifunctional sensors. [ABSTRACT FROM AUTHOR]

Background: To examine the impact of polymorphisms of glucose transporter 1 (GLUT1) gene on the prognosis of patients with stage III non‐small cell lung cancer (NSCLC) who received radiotherapy. Methods: Five single nucleotide polymorphisms (SNPs) (rs4658C>G, rs1385129G>A, rs3820589A>T, rs3806401A>C and rs3806400C>T) in GLUT1 gene were evaluated in 90 patients with pathologically confirmed stage III NSCLC. A total of 21 patients were treated with radiotherapy alone, 25 with sequential chemoradiotherapy, and 44 with concurrent chemoradiotherapy. The association of the genetic variations of five SNPs with overall survival (OS) and progression‐free survival (PFS) was analyzed. Results: Two SNPs (rs1385129 and rs3806401) were significant risk factors for OS. Three SNPs (rs1385129, rs3820589 and rs3806401) were in linkage disequilibrium. In Cox proportional hazard models, GAA haplotype was a good prognostic factor for OS (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.39–0.81, p = 0.002) and PFS (HR = 0.68, 95% CI: 0.47–0.99, p = 0.043), compared to variant haplotypes. The GAA/GAA diplotype was observed in 46.7% of patients; these patients showed significantly better OS (HR = 0.38, 95% CI: 0.22–0.65, p < 0.001) and PFS (HR = 0.51, 95% CI: 0.31–0.85, p = 0.009) compared to those with other diplotypes. Conclusions: These results suggest that polymorphisms of GLUT1 gene could be used as a prognostic marker for patients with stage III NSCLC treated with radiotherapy. [ABSTRACT FROM AUTHOR]

The octahedral structure of 2D molybdenum disulfide (1T‐MoS2) has attracted attention as a high‐efficiency and low‐cost electrocatalyst for hydrogen production. However, the large‐scale synthesis of 1T‐MoS2 films has not been realized because of higher formation energy compared to that of the trigonal prismatic phase (2H)‐MoS2. In this study, a uniform wafer‐scale synthesis of the metastable 1T‐MoS2 film is performed by sulfidation of the Mo metal layer using a plasma‐enhanced chemical vapor deposition (PE‐CVD) system. Thus, plasma‐containing highly reactive ions and radicals of the sulfurization precursor enable the synthesis of 1T‐MoS2 at 150 °C. Electrochemical analysis of 1T‐MoS2 shows enhanced catalytic activity for the hydrogen evolution reaction (HER) compared to that of previously reported MoS2 electrocatalysts 1T‐MoS2 does not transform into stable 2H‐MoS2 even after 1000 cycles of HER. The proposed low‐temperature synthesis approach may offer a promising solution for the facile production of various metastable‐phase 2D materials. [ABSTRACT FROM AUTHOR]

Background: Aβ immunotherapy is the most promising approach in treating Alzheimer's disease (AD). Although Aβ‐antibodies can substantially reduce Aβ burden in the brain, solutions for antibody‐induced inflammation and subsequent ARIA (Amyloid‐related imaging abnormalities) are still in demand. Here we developed a novel chimeric protein platform, GAIA (Gas6‐mediated anti‐inflammatory adaptor). GAIA platform utilizes TAM receptors, which are expressed on glial cells and mediate phagocytosis without associated inflammatory response. Method: We developed a GAIA‐based novel chimeric protein (αAβ‐Gas6) which is composed of two distinct functional domains; a single‐chain variable fragment of Aducanumab, which selectively binds to Aβ, fused with Gas6, a TAM receptor‐binding domain. Aβ clearance and phagocytosis‐associated inflammatory responses of αAβ‐Gas6 were measured in comparison with Aducanumab. Result: αAβ‐Gas6 showed selective uptake of Aβ through phagocytosis in vitro. While Aducanumab induced phagocytosis only in primary microglia, αAβ‐Gas6 significantly induced phagocytosis in both cultured microglia and astrocyte. In comparison with Aducanumab, αAβ‐Gas6 secreted significantly lower amount of pro‐inflammatory cytokines, such as TNF, IL‐6, and IL‐1β. In vivo application of αAβ‐Gas6 reduced Aβ burden in an extent significantly lower in mice treated with Aducanumab. Finally, αAβ‐Gas6 groups showed significantly reduced excessive synapse elimination levels comparable to non‐AD wild type groups. Conclusion: We developed a novel chimeric fusion protein αAβ‐Gas6 by engineering TAM receptor‐binding domain Gas6. In comparison with antibody drug, αAβ‐Gas6 showed advanced amyloid clearance, significantly reduced neuroinflammation, and neurotoxicity. Thus, our results suggest a novel immunotherapeutic agent which can bifunctionally target Aβ and modulate gilal cells to reduce neuroinflammation. [ABSTRACT FROM AUTHOR]

Background: With organismal aging, the hypothalamic–pituitary–gonadal (HPG) activity gradually decreases, resulting in the systemic functional declines of the target tissues including skeletal muscles. Although the HPG axis plays an important role in health span, how the HPG axis systemically prevents functional aging is largely unknown. Methods: We generated muscle stem cell (MuSC)‐specific androgen receptor (Ar) and oestrogen receptor 2 (Esr2) double knockout (dKO) mice and pharmacologically inhibited (Antide) the HPG axis to mimic decreased serum levels of sex steroid hormones in aged mice. After short‐term and long‐term sex hormone signalling ablation, the MuSCs were functionally analysed, and their aging phenotypes were compared with those of geriatric mice (30‐month‐old). To investigate pathways associated with sex hormone signalling disruption, RNA sequencing and bioinformatic analyses were performed. Results: Disrupting the HPG axis results in impaired muscle regeneration [wild‐type (WT) vs. dKO, P < 0.0001; Veh vs. Antide, P = 0.004]. The expression of DNA damage marker (in WT = 7.0 ± 1.6%, dKO = 32.5 ± 2.6%, P < 0.01; in Veh = 13.4 ± 4.5%, Antide = 29.7 ± 5.5%, P = 0.028) and senescence‐associated β‐galactosidase activity (in WT = 3.8 ± 1.2%, dKO = 10.3 ± 1.6%, P < 0.01; in Veh = 2.1 ± 0.4%, Antide = 9.6 ± 0.8%, P = 0.005), as well as the expression levels of senescence‐associated genes, p16Ink4a and p21Cip1, was significantly increased in the MuSCs, indicating that genetic and pharmacological inhibition of the HPG axis recapitulates the progressive aging process of MuSCs. Mechanistically, the ablation of sex hormone signalling reduced the expression of transcription factor EB (Tfeb) and Tfeb target gene in MuSCs, suggesting that sex hormones directly induce the expression of Tfeb, a master regulator of the autophagy–lysosome pathway, and consequently autophagosome clearance. Transduction of the Tfeb in naturally aged MuSCs increased muscle mass [control geriatric MuSC transplanted tibialis anterior (TA) muscle = 34.3 ± 2.9 mg, Tfeb‐transducing geriatric MuSC transplanted TA muscle = 44.7 ± 6.7 mg, P = 0.015] and regenerating myofibre size [eMyHC+tdTomato+ myofibre cross‐section area (CSA) in control vs. Tfeb, P = 0.002] after muscle injury. Conclusions: Our data show that the HPG axis systemically controls autophagosome clearance in MuSCs through Tfeb and prevents MuSCs from senescence, suggesting that sustained HPG activity throughout life regulates autophagosome clearance to maintain the quiescence of MuSCs by preventing senescence until advanced age. [ABSTRACT FROM AUTHOR]