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Controlling electron density in two-dimensional semiconductors is crucial for both comprehensive understanding of fundamental material properties and their technological applications. However, conventional electrostatic doping methods exhibit limitations, particularly in addressing electric field-induced drift and subsequent diffusion of electrons, which restrict nanoscale doping. Here, we present a tip-induced nanospectroscopic electric pulse modulator to dynamically control nanoscale electron density, thereby facilitating precise measurement of nano-optoelectronic behaviors within a MoS 2 monolayer. The tip-induced electric pulse enables nanoscale modulation of electron distribution as a function of electric pulse width. We simultaneously investigate spatially altering photoluminescence quantum yield at the nanoscale region. We model the extent of electron depletion region, confirming a minimum doping region with a radius of ∼265 nanometers for a 30-nanosecond pulse width. Our approach paves the way for engineering local electron density and in situ nano-optical characterization in two-dimensional materials, enabling an in-depth understanding of doping-dependent nano-optoelectronic phenomena.

Background: Liposomal bupivacaine (LB) is a long-lasting local anesthetic agent that was developed for use in the surgical setting to help manage postoperative pain. The objective of this study was to evaluate the effect of LB on postoperative pain, function, and overall hospital course in patients with intracapsular hip fractures who were treated with hip hemiarthroplasty., Methods: This was a single-center, randomized prospective double-blinded study of 50 patients with an isolated intracapsular femoral neck fracture who were treated with hip hemiarthroplasty from 2018 to 2022. The study group consisted of 25 patients who were treated with intraoperative LB and bupivacaine hydrochloride injections, while the control group consisted of 25 patients who were treated with intraoperative bupivacaine hydrochloride injections only. Primary outcomes were a visual analog scale (VAS) score for pain, total morphine milligram equivalents (MME), delirium, and time to ambulation with physical therapy., Results: No significant differences between the study and control groups were found in any of the outcomes measured. Most notably, there were no differences in the average postoperative pain score (VAS, 2.26 versus 2.7; p = 0.34), total MME used postoperatively (11.73 versus 9.98 MME; p = 0.71), and postoperative day of discharge (4.00 versus 3.88 days; p = 0.82)., Conclusions: The results of our study suggest that use of LB is not associated with substantially improved postoperative pain or function or with a shorter hospital course following hip hemiarthroplasty for a femoral neck fracture. Given the higher cost of LB compared with standard postoperative pain modalities, it is worth questioning its use in the setting of geriatric hip fractures., Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: No external funding was received for this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/I173 )., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Melon (Cucumis melo L.), an important cucurbit crop, faces production limitations due to powdery mildew (PM). Developing resistant varieties offers a sustainable, genetics-based alternative to chemical treatments. Therefore, identifying PM resistance quantitative trait loci (QTL) and creating trait-associated markers are essential for efficient melon PM resistance improvement through marker-assisted backcrossing (MABC)., Results: Three F 2 populations, A6, B2, and C4, were generated for QTL mapping of PM resistance. Major QTL were identified on chromosome 2 in A6, chromosome 5 in B2, and chromosomes 5 and 12 in C4. A series of TaqMan® assays targeting regions on chromosomes 2, 5, and 12 were developed and validated for foreground and recombinant selection, complemented by the double digest restriction-site associated DNA genotyping system to evaluate the recurrent parent genome recovery. Three MABC programs using resistant donor parents from A6 and C4 crossed with elite susceptible recurrent parents with green and orange fruit flesh were implemented. After two to three cycles of MABC, individual QTL was successfully introgressed into elite genetic backgrounds, giving six PM resistance lines in each green- and orange-fleshed background. PM inoculation on the twelve near-isogenic lines confirmed their resistance to PM., Conclusions: We have identified major PM resistance QTL for melon on chromosomes 2, 5, and 12 and have introgressed individual QTL to elite genetic backgrounds using MABC in three and a half years. This study demonstrates the power of combining high-throughput genotyping with breeding efforts and showcases the efficiency of molecular breeding., (© 2024. The Author(s).)

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes possess therapeutic potential against degenerative diseases. This study aimed to investigate the effects of BMSC-derived exosomes on intervertebral disc degeneration (IVDD) and explore the underlying molecular mechanisms. Through transcriptome sequencing and histological analysis, we observed a significant increase in HIF-1α expression in degenerative nucleus pulposus (NP) tissues. The addition of HIF-1α resulted in elevated expression of inflammatory factors IL-1β and IL-6, higher levels of matrix-degrading enzyme MMP13, and lower expression of aggrecan in NP cells. Co-culturing with BMSCs diminished the expression of HIF-1α, MMP13, IL-1β, and IL-6 in degenerative NP cells induced by overload pressure. miRNA chip analysis and PCR validation revealed that miR-145a-5p was the primary miRNA carried by BMSC-derived exosomes. Overexpression of miR-145a-5p was effective in minimizing the expression of HIF-1α, MMP13, IL-1β, and IL-6 in degenerative NP cells. Luciferase reporter assays confirmed USP31 as the target gene of miR-145a-5p, and the regulation of NP cells by BMSC-derived exosomes via miR-145a-5p was dependent on USP31. In conclusion, BMSC-derived exosomes alleviated IVDD through the miR-145a-5p/USP31/HIF-1α signaling pathway, providing valuable insights into the treatment of IVDD., Competing Interests: Declarations Ethical Approval The nucleus pulposus specimens were collected with the approval of the Ethics Committee of the First Affiliated Hospital of the Air Force Medical University of the People’s Liberation Army (Approval number: KY20222063-D-2) and written informed consent was obtained from the specimen donors or their families. All experimental processes were performed with the Guide for the Care and Use of Laboratory Animals (National Institutes of Health, eighth edition, 2011), and approved by the Ethics Committee of the First Affiliated Hospital of the Air Force Medical University of the People’s Liberation Army (Approval number: KY20222063-D-2). Consent for Publication The authors affirm that all participants provided informed consent for publication of the paper. Consent to Participate Informed consent was obtained from all individual participants included in the study. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Based on the varying number and relative positions of cervical disc replacement (CDR) and anterior cervical discectomy and fusion (ACDF) procedures, three-segment hybrid surgery (HS) presents a diverse structural approach. Currently, the potential differential effects of HS with different segment combinations and surgical procedures on overloaded vertebral body (OVB) occurrence remain unexplored. The purpose of this retrospective study is to compare the clinical and radiological outcomes of HS and ACDF in treating cervical degenerative disc disease (CDDD), aiming to provide further insights into OVB., Methods: This study included patients with three-level CDDD who underwent ACDF or HS at our institution. Eligible patients were divided into three groups: Type I (one-level CDR and two-level ACDF), Type II (two-level CDR and one-level ACDF), and ACDF (three-level ACDF). For radiographic analysis, patients were further divided into the Replacement Segment Group and the Nonreplacement Segment Group based on the presence of replacement segments above and below the OVB. Clinical outcomes were evaluated using visual analog scale (VAS) scores for neck and arm pain, Japanese Orthopedic Association (JOA) scores, and neck disability index (NDI) scores. The cervical radiological parameters assessed included (1) vertebral cross-sectional area (CSA), (2) wedge angle (WA), (3) anterior vertebral height (AH), (4) posterior vertebral height (PH), and (5) Hounsfield unit (HU) values. Statistical methods included paired t-test, ANOVA test, and chi-square test. Independent samples t-test, Mann-Whitney U test, and Wilcoxon signed-rank test were used to compare the differences between two groups according to the results of normal distribution test., Results: A total of 123 patients, evenly distributed among three groups, were included and were well matched in terms of demographic characteristics. The likelihood of vertebral body collapse (VBC) was notably higher in the ACDF group (41.5%) compared with the Type I (17.9%) and Type II (8.9%) groups (p < 0.01). Following surgery, both at 3 and 6 months, the ACDF group demonstrated higher VAS neck scores and NDI scores compared with the Type I and Type II groups (p < 0.01). Additionally, the WA and AH values of the upper and lower adjacent OVB were consistently lower in the ACDF group than in the Type I and Type II groups at 6 and 12 months and at the final follow-up (p < 0.01). Notably, in the Nonreplacement Segment Group, WA significantly decreased at 12 months postoperatively and at the final follow-up compared with the Replacement Segment Group (p < 0.01)., Conclusions: Three levels of HS appear to reduce stress concentrations and alleviate morphological changes in OVB. The occurrence of more VBC patients with OVB was associated with the use of Zero-P or Zero-P VA implants., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

High-speed electrical control of nano-optoelectronic properties in two-dimensional semiconductors is a building block for the development of excitonic devices, allowing the seamless integration of nano-electronics and -photonics. Here, we demonstrate a high-speed electrical modulation of nanoscale exciton behaviors in a MoS 2 monolayer at room temperature through a quantum tunneling nanoplasmonic cavity. Electrical control of tunneling electrons between Au tip and MoS 2 monolayer facilitates the dynamic switching of neutral exciton- and trion-dominant states at the nanoscale. Through tip-induced spectroscopic analysis, we locally characterize the modified recombination dynamics, resulting in a significant change in the photoluminescence quantum yield. Furthermore, by obtaining a time-resolved second-order correlation function, we demonstrate that this electrically-driven nanoscale exciton-trion interconversion achieves a modulation frequency of up to 8 MHz. Our approach provides a versatile platform for dynamically manipulating nano-optoelectronic properties in the form of transformable excitonic quasiparticles, including valley polarization, recombination, and transport dynamics., (© 2024. The Author(s).)

Purpose: Hand-sewn anastomosis as the gold standard of vascular anastomosis cannot fully meet the requirements of vascular anastomosis in speed and quality. Various vascular couplers have been developed to ameliorate this situation. Most of them are mainly used for venous anastomosis rather than arterial anastomosis, even though it is generally acknowledged that in almost all operations involving vascular reconstruction, it is the arteries that need to be anastomosed faster and more accurately and not the veins. A dedicated device is needed for creating arterial anastomosis in an easy, timesaving, less damaging but reliable procedure. Therefore, we plan to develop a novel arterial coupler device and test pre-clinical safety and effectiveness., Methods: In this cohort study, the rationality of this novel arterial coupler was preliminarily tested by finite element analysis before it was manufactured. Several factors restrict the use of vascular couplers in arterial anastomosis, such as arterial eversion, fixation, etc. The manufactured arterial couplers underwent in vitro and in vivo experiments. In vitro, isolated arteries of beagles were anastomosed with the assistance of an arterial coupler, and the anastomosed arteries were evaluated through anti-traction tests. In animal experiments, the bilateral femoral arteries of 5 beagles served as a control group. After dissection, the femoral artery on one side was randomly selected to be anastomosed with a quick arterial coupler (QAC) (QAC group), and the femoral artery on the other side was anastomosed by the same person using an end-to-end suture technique with a 6-0 Prolene suture (suture group). The bilateral femoral arteries of 5 beagles were used for coupler-assisted anastomosis and hand-sewn anastomosis in vivo, respectively. Success rate, blood loss, anastomotic time, clamp time, total operation time, and patency rate were recorded. The patency of anastomosed arteries was assessed using vascular Doppler ultrasound, electromagnetic flowmeter, and pathological examination (6 weeks after surgery)., Results: As a novel arterial coupler, QAC was successfully designed and manufactured by using poly lactic-co-glycolic acid raw materials and 3-dimensions printing technology. Its rationality was preliminarily tested through finite element analysis and related mechanical analysis methods. The isolated arteries were successfully anastomosed with the assistance of QAC in vitro testing, which showed good anti-traction properties. In animal studies, QAC-assisted arterial anastomosis has superior profiles compared to hand-sewn anastomosis in anastomotic time (7.80 ± 1.41 vs. 16.38 ± 1.04 min), clamp time (8.80 ± 1.41 vs. 14.14 ± 1.57 min), and total operation time (46.64 ± 2.38 vs. 51.96 ± 3.65 min). The results of electromagnetic flowmeter, vascular Doppler ultrasound, and pathological examination showed that QAC-assisted anastomotic arteries were superior to hand-sewn arteries in terms of postoperative blood flow (16.86 ± 3.93 vs. 10.36 ± 0.92 mL/min) and vascular patency in 6 weeks after surgery., Conclusion: QAC is a well-designed and easily maneuverable device specialized for end-to-end arterial anastomosis. Application of this device may decrease thermal ischemia time and improve the patency of anastomotic arteries, thus, improving outcomes., Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2024. Published by Elsevier B.V.)

VP1, a major immunogenic protein of foot-and-mouth disease virus (FMDV), facilitates viral attachment and entry into host cells. VP1 possesses critical epitope sequences responsible for inducing neutralizing antibodies but its expression using Saccharomyces cerevisiae has been hampered despite evidence that the presence of VP1 does not negatively impact the yeast's biology. In this study, we fused proteins to enhance VP1 expression using S. cerevisiae. Among short P1 chimeras containing VP1 including VP3-VP1 and VP2-VP1, VP3-VP1 fusion proteins showed higher expression levels than VP2-VP1. We subsequently designed new fusion proteins, of which 20 amino acids of N-terminal VP3 fused with VP1-Co1 (referred to 20aaVP3-VP1-Co1) showed the highest expression level. Lowering the culture temperature from 30 ⁰C to 20 ⁰C further enhanced fusion protein production. The highest expression level of 20aaVP3-VP1-Co1 was estimated to be 7.7 mg/L, which is comparable to other heterologous proteins produced using our S. cerevisiae expression system. Oral administration of the cell expressing 20aaVP3-VP1-Co1 induced VP1-specific IgG and IgA responses in mice. The S. cerevisiae-expressed 20aaVP3-VP1-Co1 fusion protein induced a significant immune response to the FMDV structural epitope protein, which opens the possibility of an oral FMDV vaccine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: MicroRNA (miRNA) pathway genes have been widely reported to participate in several physiological events in insect lifecycles. The cigarette beetle Lasioderma serricorne is an economically important storage pest worldwide. However, the functions of miRNA pathway genes in L. serricorne remain to be clarified. Herein, we investigated the function of molting and reproduction of the miRNA pathway in L. serricorne., Results: LsDicer-1, LsArgonaute-1, LsLoquacious and LsExportin-5 were universally expressed in adults, whereas LsPasha and LsDrosha were mainly expressed in the pupae. The genes presented different patterns in various tissues. Silencing of LsDicer-1, LsArgonaute-1, LsDrosha and LsExportin-5 resulted in a high proportion of wing deformities and molting defects. Silencing of LsDicer-1, LsArgonaute-1, LsPasha and LsLoquacious affected the development of the ovary and the maturation of oocytes, resulting in a significant decrease in fecundity. Further investigation revealed that the decreases in LsDicer-1 and LsArgonaute-1 expression destroyed follicular epithelia and delayed vitellogenesis and oocyte development. In addition, the expression levels of several miRNAs (let-7, let-7-5p, miR-8-3p, miR-8-5p, miR-9c-5p, miR-71, miR-252-5p, miR-277-3p, miR-263b and Novel-miR-50) were decreased significantly after knockdown of these miRNA pathway core genes, indicating that they played important roles in regulating miRNA-mediated gene expression., Conclusion: The results indicate that miRNA pathway genes play important roles in the molting, ovarian development and female fecundity of L. serricorne, and thus are potentially suitable target genes for developing an RNAi strategy against a major pest of stored products. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

We engineered Saccharomyces cerevisiae to express structural proteins of foot-and-mouth disease virus (FMDV) and produce virus-like particles (VLPs). The gene, which encodes four structural capsid proteins (VP0 (VP4 and VP2), VP3, and VP1), followed by a translational "ribosomal skipping" sequence consisting of 2A and protease 3C, was codon-optimized and chemically synthesized. The cloned gene was used to transform S. cerevisiae 2805 strain. Western blot analysis revealed that the polyprotein consisting of VP0, VP3, and VP1 was processed into the discrete capsid proteins. Western blot analysis of 3C confirmed the presence of discrete 3C protein, suggesting that the 2A sequence functioned as a "ribosomal skipping" signal in the yeast for an internal re-initiation of 3C translation from a monocistronic transcript, thereby indicating polyprotein processing by the discrete 3C protease. Moreover, a band corresponding to only VP2, which was known to be non-enzymatically processed from VP0 to both VP4 and VP2 during viral assembly, further validated the assembly of processed capsid proteins into VLPs. Electron microscopy showed the presence of the characteristic icosahedral VLPs. Our results clearly demonstrate that S. cerevisiae processes the viral structural polyprotein using a viral 3C protease and the resulting viral capsid subunits are assembled into virion particles. KEY POINTS: • Ribosomal skipping by self-cleaving FMDV peptide in S. cerevisiae. • Proteolytic processing of a structural polyprotein from a monocistronic transcript. • Assembly of the processed viral capsid proteins into a virus-like particle., (© 2024. The Author(s).)

Although pulmonary adenomas have been reported in ICR mice, spontaneous adenomas have not been reported in mice aged ≤10 weeks. Here, we report a well-circumscribed nodule (1 mm × 1 mm) in the peripheral lesion of the left lateral lobe of a 10-week-old male ICR mouse. Histopathologic evaluation revealed a well-demarcated nodule compressing the surrounding tissue. The neoplastic cells were polygonal with indistinct cellular borders, round/oval nuclei and abundant cytoplasm. These characteristics led to the diagnosis of type II cell-derived bronchioloalveolar adenoma. Given that they are generally observed in aged laboratory animals, this case represents a rare manifestation of a spontaneous tumor in young laboratory mice before puberty., Competing Interests: Declaration of conflicting interestsThe authors have no conflicts of interest to declare.

Objective: This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance., Methods: A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data., Results: In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model., Conclusion: Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD., (© 2024. The Author(s).)

Recently, 2D semiconductor-based optoelectronic memory has been explored to overcome the limitations of conventional von Neumann architectures by integrating optical sensing and data storage into one device. Persistent photocurrent (PPC), essential for optoelectronic memory, originates from charge carrier trapping according to the Shockley-Read-Hall (SRH) model in 2D semiconductors. The quasi-Fermi level position influences the activation of charge-trapping sites. However, the correlation between quasi-Fermi level modulations and PPC in 2D semiconductors has not been extensively studied. In this study, we demonstrate optoelectronic memory based on a 2D semiconductor-polymer hybrid structure and confirm that the underlying mechanism is charge trapping, as the SRH model explains. Under light illumination, electrons transfer from polyvinylpyrrolidone to p-type tungsten diselenide, resulting in high-level injection and majority carrier-type transitions. The quasi-Fermi level shifts upward with increasing temperature, improving PPC and enabling optoelectronic memory at 433 K. Our findings offer valuable insights into optimizing 2D semiconductor-based optoelectronic memory.

Background: The pathogenesis of noncystic fibrosis bronchiectasis in adults is complex, and the relevant molecular mechanisms remain unclear. In this study, we constructed a panoramic map of bronchiectasis mRNA, explored the potential molecular mechanisms, and identified potential therapeutic targets, thus providing a new clinical perspective for the preventive management of bronchiectasis and its acute exacerbation., Methods: The mRNA profiles of peripheral blood and bronchiectasis tissues were obtained through transcriptome sequencing and public databases, and bioinformatics methods were used to screen for differentially expressed genes (DEGs). The DEGs were then subjected to biological function and pathway analyses. Some DEGs were validated using a real-time quantitative polymerase chain reaction (RT-qPCR) in peripheral blood. Spearman's correlation analysis was used to analyse the correlation between DEGs and clinical indicators., Results: Based on transcriptome sequencing and public databases, the mRNA profile of bronchiectasis was determined. DEGs were obtained from the peripheral blood sequencing dataset (985 DEGs), tissue sequencing dataset (2919 DEGs), and GSE97258 dataset (1083 DEGs). Bioinformatics analysis showed that upregulated DEGs had enriched neutrophil-related pathways, and downregulated DEGs had enriched ribosome-related pathways. RT-qPCR testing confirmed the upregulated expression of VCAN, SESTD1, SLC12A1, CD177, IFI44L, SIGLEC1, and RSAD2 in bronchiectasis. These genes were related to many clinical parameters, such as neutrophils, C-reactive protein, and procalcitonin (P < 0.05)., Conclusions: Transcriptomic methods were used to construct a panoramic map of bronchiectasis mRNA expression. The findings showed that neutrophil activation, chronic inflammation, immune regulation, impaired ribosomal function, oxidative phosphorylation, and energy metabolism disorders are important factors in the development of bronchiectasis. VCAN, SESTD1, SLC12A1, CD177, IFI44L, SIGLEC1, and RSAD2 may play important roles in the pathogenesis of bronchiectasis and are potential therapeutic targets., (© 2024. The Author(s).)

Researchers are increasingly interested in cell therapy using mesenchymal stem cells (MSCs) as an alternative remedy for osteoporosis, with fewer side effects. Thus, we isolated and characterized extracellular vesicles (EVs) from human adipose tissue-derived MSCs (hMSCs) and investigated their inhibitory effects on RANKL-induced osteoclast differentiation. Purified EVs were collected from the supernatant of hMSCs by tangential flow filtration. Characterization of EVs included typical evaluation of the size and concentration of EVs by nanoparticle tracking analysis and morphology analysis using transmission electron microscopy. hMSC-EVs inhibited RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by EV treatment of osteoclasts. In addition, EVs decreased RANKL-induced phosphorylation of p38 and JNK and expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. To elucidate which part of the hMSC-EVs plays a role in the inhibition of osteoclast differentiation, we analyzed miRNA profiles in hMSC-EVs. The results showed that has-miR122-5p was present at significantly high read counts. Overexpression of miR122-5p in BMDMs significantly inhibited RANKL-induced osteoclast differentiation and induced defects in F-actin ring formation and bone resorption. Our results also revealed that RANKL-induced phosphorylation of p38 and JNK and osteoclast-specific gene expression was decreased by miR122-5p transfection, which was consistent with the results of hMSC-EVs. These findings suggest that hMSC-EVs containing miR122-5p inhibit RANKL-induced osteoclast differentiation via the downregulation of molecular mechanisms and could be a preventive candidate for destructive bone diseases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

G-quadruplex structures within the nuclear genome (nG4) is an important regulatory factor, while the function of G4 in the mitochondrial genome (mtG4) still needs to be explored, especially in human sperms. To gain a better understanding of the relationship between mtG4 and mitochondrial function, it is crucial to develop excellent probes that can selectively visualize and track mtG4 in both somatic cells and sperms. Herein, based on our previous research on purine frameworks, we attempted for the first time to extend the conjugated structure from the C-8 site of purine skeleton and discovered that the purine derivative modified by the C-8 aldehyde group is an ideal platform for constructing near-infrared probes with extremely large Stokes shift (>220 nm). Compared with the compound substituted with methylpyridine (PAP), the molecule substituted with methylthiazole orange ( PATO ) showed better G4 recognition ability, including longer emission (∼720 nm), more significant fluorescent enhancement (∼67-fold), lower background, and excellent photostability. PATO exhibited a sensitive response to mtG4 variation in both somatic cells and human sperms. Most importantly, PATO helped us to discover that mtG4 was significantly increased in cells with mitochondrial respiratory chain damage caused by complex I inhibitors (6-OHDA and rotenone), as well as in human sperms that suffer from oxidative stress. Altogether, our study not only provides a novel ideal molecular platform for constructing high-performance probes but also develops an effective tool for studying the relationship between mtG4 and mitochondrial function in both somatic cells and human sperms.

Use of a template triggers an epitaxial interaction with the depositing material during synthesis. Recent studies have demonstrated that two-dimensional tellurium (tellurene) can be directionally oriented when grown on transition metal dichalcogenide (TMD) templates. Specifically, employing a T-phase TMD, such as WTe 2 , restricts the growth direction even further due to its anisotropic nature, which allows for the synthesis of well-oriented tellurene films. Despite this, producing large-area epitaxial films still remains a significant challenge. Here, we report the continuous synthesis of a 1T'-MoTe 2 template via chemical vapor deposition and tellurene via vapor transport. The interaction between helical Te and the 1T'-MoTe 2 template facilitates the Te chains to collapse into ribbon shapes, enhancing lateral growth at a rate approximately 6 times higher than in the vertical direction, as confirmed by scanning electron microscopy and atomic force microscopy. Interestingly, despite the predominance of the lateral growth, cross-sectional transmission electron microscopy analysis of the tellurene ribbons revealed a consistent 60-degree incline at the edges. This suggests that the edges of the tellurene ribbons, where they contact the template surface, are favorable sites for additional Te absorption, which then stacks along the incline angle to expand. Furthermore, controlling the synthesis temperature, duration, and preheating time has facilitated the successful synthesis of tellurene films. The resultant tellurene exhibited hole mobility as high as ∼400 cm 2 /V s. After removing the underlying metallic template with plasma treatment, the film showed a current on/off ratio of ∼10 3 . This ratio was confirmed by two-terminal field-effect transistor measurements and supported by near-field terahertz (THz) spectroscopy mapping.

Archaeological excavations led by Yung-jo Lee and Jong-yoon Woo were carried out twice at the Sorori paleolithic site, Cheongju, in the Republic of Korea, at the upper stream of the Geumgang river, the Miho riverside. A total of 127 rice seeds were excavated, including 18 ancient rice and 109 Quasi-rice, in 1998 and 2001. At the first excavation, eleven short japonica -type ancient rice and one slender smooth ancient rice with two kinds of Quasi-rice were excavated. The average length of the 11 short rice grains obtained from the first and second excavation was 7.19 mm and the average width was 3.08 mm, respectively. The Quasi-rice are apparently different from the rice and do not have bi-peak protuberances on their glume surface. At the second excavation, six short ancient rice chaffs and some Quasi-rice 2 were found. These short-grained ancient rice were comparable to the ancient rice that were excavated at the Illsan Neolithic site. Geologists and radiologists confirmed that the peat layer in which the rice found was older than 15,000 years. In this study, the morphological characteristics, crushing, and DNA band patterns related to the genetic polymorphism of rice grains in Cheongju Sorori were compared and analyzed for genetic similarities and differences with wild rice, weed rice, and modern rice. The morphological, ecological, and physiological variations in rice grains excavated from the Sorori site were presumed to denote the origin of rice domestication in Korea. It is also suggested that the results of the DNA sequencing of excavated rice are very important clues in estimating the origin of the early domestication of rice.

Atomic sawtooth surfaces have emerged as a versatile platform for growth of single-crystal van der Waals layered materials. However, the mechanism governing the formation of single-crystal atomic sawtooth metal (copper or gold) films on hard substrates (tungsten or molybdenum) remains a puzzle. In this study, we aim to elucidate the formation mechanism of atomic sawtooth metal films during melting-solidification process. Utilizing molecular dynamics, we unveil that the solidification of the liquid copper initiates at a high-index tungsten facet with higher interfacial energy. Subsequent tungsten facets follow energetically favourable pathways of forming single-crystal atomic sawtooth copper film during the solidification process near melting temperature. Formation of atomic sawtooth copper film is guaranteed with a film thickness exceeding the grain size of polycrystalline tungsten substrate. We further demonstrate the successful growth of centimeter-scale single-crystal monolayer hexagonal boron nitride films on atomic sawtooth copper films and explore their potential as efficient oxygen barrier., (© 2024. The Author(s).)

Ubiquitination plays a crucial role in regulating signal pathways during the post-translation stage of protein synthesis in response to various environmental stresses. E3 ubiquitin ligase has been discovered to ultimately control various intracellular activities by imparting specificity to proteins to be degraded. This study was conducted to confirm biological and genetic functions of the U-box type E3 ubiquitin ligase (PUB) gene against biotic stress in rice ( Oryza sativa L.). OsPUB9 gene-specific sgRNA were designed and transformants were developed through Agrobacterium -mediated transformation. Deep sequencing using callus was performed to confirm the mutation type of T 0 plants, and a total of three steps were performed to select null individuals without T-DNA insertion. In the case of the OsPUB9 gene-edited line, a one bp insertion was generated by gene editing, and it was confirmed that early stop codon and multiple open reading frame (ORF) sites were created by inserting thymine. It is presumed that ubiquitination function also changed according to the change in protein structure of U-box E3 ubiquitin ligase. The OsPUB9 gene-edited null lines were inoculated with bacterial leaf blight, and finally confirmed to have a resistance phenotype similar to Jinbaek, a bacterial blight-resistant cultivar. Therefore, it is assumed that the amino acid sequence derived from the OsPUB9 gene is greatly changed, resulting in a loss of the original protein functions related to biological mechanisms. Comprehensively, it was confirmed that resistance to bacterial leaf blight stress was enhanced when a mutation occurred at a specific site of the OsPUB9 gene.

Background: The aim of the study was to investigate the muscle differences in children with osteogenesis imperfecta (OI) using opportunistic low-dose chest CT and to compare different methods for the segmentation of muscle in children., Methods: This single center retrospective study enrolled children with OI and controls undergoing opportunistic low-dose chest CT obtained during the COVID pandemic. From the CT images, muscle size (cross-sectional area) and density (mean Hounsfield Units [HU]) of the trunk muscles were measured at the mid-T4 and the mid-T10 level using two methods, the fixed thresholds and the Gaussian mixture model. The Bland-Altman method was also used to compute the strength of agreement between two methods. Comparison of muscle results between OI and controls were analyzed with Student t tests., Results: 20 children with OI (mean age, 9.1 ± 3.3 years, 15 males) and 40 age- and sex-matched controls were enrolled. Mean differences between two methods were good. Children with OI had lower T4 and T10 muscle density than controls measured by the fixed thresholds (41.2 HU vs. 48.0 HU, p < 0.01; 37.3 HU vs. 45.9 HU, p < 0.01). However, children with OI had lower T4 muscle size, T4 muscle density, T10 muscle size and T10 muscle density than controls measured by the Gaussian mixture model (110.9 vs. 127.2 cm 2 , p = 0.03; 44.6 HU vs. 51.3 HU, p < 0.01; 72.6 vs. 88.0 cm 2 , p = 0.01; 41.6 HU vs. 50.3 HU, p < 0.01, respectively)., Conclusions: Children with OI had lower trunk muscle density indicating that OI might also impair muscle quality. Moreover, the fixed thresholds may not be suitable for segmentation of muscle in children., (© 2024. The Author(s).)

The properties of transition metal dichalcogenides (TMDCs) are critically dependent on the dielectric constant of substrates, which significantly limits their application. To address this issue, we used a perfluorinated polyether (PFPE) self-assembled monolayer (SAM) with low surface energy to increase the van der Waals (vdW) gap between TMDCs and the substrate, thereby reducing the interaction between them. This resulted in a reduction in the subthreshold swing value, an increase in the photoluminescence intensity of excitons, and a decrease in the doping effect by the substrate. This work will provide a new way to control the TMDC/dielectric interface and contribute to expanding the applicability of TMDCs.

Background: Avascular necrosis (AVN) is a medical condition characterized by the destruction of bone tissue due to a diminished blood supply. When the rate of tissue destruction surpasses the rate of regeneration, effective treatment becomes challenging, leading to escalating pain, arthritis, and bone fragility as the disease advances. A timely diagnosis is imperative to prevent and initiate proactive treatment for osteonecrosis. We explored the potential of differentially expressed proteins in serum-derived extracellular vesicles (EVs) as biomarkers for AVN of the femoral head in humans. We analyzed the genetic material contained in serum-derived exosomes from patients for early diagnosis, treatment, and prognosis of avascular necrosis., Methods: EVs were isolated from the serum of both patients with AVN and a control group of healthy individuals. Proteomic analyses were conducted to compare the expression patterns of these proteins by proteomic analysis using LC-MS/MS., Results: Our results show that the levels of IGHV3-23, FN1, VWF, FGB, PRG4, FCGBP, and ZSWIM9 were upregulated in the EVs of patients with AVN compared with those of healthy controls. ELISA results showed that VWF and PRG4 were significantly upregulated in the patients with AVN., Conclusions: These findings suggest that these EV proteins could serve as promising biomarkers for the early detection and diagnosis of AVN. Early diagnosis is paramount for effective treatment, and the identification of new osteonecrosis biomarkers is essential to facilitate swift diagnosis and proactive intervention. Our study provides novel insights into the identification of AVN-related biomarkers that can enhance clinical management and treatment outcomes., (© 2024. The Author(s).)

A novel bacterial strain, designated as MAH-18 T , was isolated from soil sampled in a flower garden. Cells of strain MAH-18 T were Gram-stain-positive, aerobic, motile, and rod-shaped. The colonies were beige in colour, smooth, and spherical when grown on Reasoner's 2A agar medium. Strain MAH-18 T grew at 20-40 °C, pH 6.0-8.0, and 0-1.0 % NaCl. Cells were able to hydrolyse aesculin, gelatin, and Tween 20. According to the 16S rRNA gene sequence comparisons, the isolate was determined to be a member of the genus Nocardioides and most closely related to Nocardioides pyridinolyticus OS4 T (97.9 %), Nocardioides hankookensis DS-30 T (97.9 %), Nocardioides aquiterrae GW-9 T (97.6 %), Nocardioides soli mbc-2 T (97.5 %), Nocardioides conyzicola HWE 2-02 T (97.4 %), and Nocardioides mangrovi GBK3QG-3 T (96.3 %). Strain MAH-18 T has a draft genome size of 4 788 325 bp (eight contigs), 4572 protein-coding genes, 46 tRNA, and three rRNA genes. The average nucleotide identity and digital DNA-DNA hybridization values between strain MAH-18 T and the closest type strains were 81.5-83.4 % and 24.4-25.8 %, respectively. In silico genome mining revealed several biosynthetic gene clusters in the genome of the novel strain MAH-18 T . The G+C content of the genomic DNA of strain was 72.2 mol% and the predominant isoprenoid quinone was MK-8 (H 4 ). The main polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, and unknown phospholipids. The major cellular fatty acids were determined to be C 16:0 iso and C 17 : 1  ω 6 c . The DNA-DNA hybridization results and phenotypic, genotypic, and chemotaxonomic data demonstrated that strain MAH-18 T represents a novel species, for which the name Nocardioides agri sp. nov. is proposed, with MAH-18 T as the type strain (=KACC 19744 T =CGMCC 1.13656 T ).

Nuclear receptors (NRs) are ligand-regulated transcription factors that are important for the normal growth and development of insects. However, systematic function analysis of NRs in the molting process of Lasioderma serricorne has not been reported. In this study, we identified and characterized 16 NR genes from L. serricorne. Spatiotemporal expression analysis revealed that six NRs were mainly expressed in 3-d-old 4th-instar larvae; five NRs were primarily expressed in 5-d-old adults and four NRs were predominately expressed in prepupae. All the NRs were highly expressed in epidermis, fat body and foregut. RNA interference (RNAi) experiments revealed that knockdown of 15 NRs disrupted the larva-pupa-adult transitions and caused 64.44-100 % mortality. Hematoxylin-eosin staining showed that depletion of 12 NRs prevented the formation of new cuticle and disrupted apolysis of old cuticle. Silencing of LsHR96, LsSVP and LsE78 led to newly formed cuticle that was thinner than the controls. The 20E titer and chitin content significantly decreased by 17.67-95.12 % after 15 NR dsRNA injection and the gene expression levels of 20E synthesis genes and chitin metabolism genes were significantly reduced. These results demonstrated that 15 NR genes are essential for normal molting and metamorphosis of L. serricorne by regulating 20E synthesis and chitin metabolism., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: A growing number of studies have examined the relation between solid fuels use and cognitive function in the mid-elderly, but results are inconsistent. Therefore, a systematic review and meta-analysis was carried out to evaluate their relevance and the efficacy of switching to cleaner fuels or using ventilation., Method: We used PubMed, Web of Science, and Cochrane Library databases to identify 17 studies in which the primary outcome variable was cognitive function decline or cognitive disorders, and the exposure measure was solid fuels use. The final search date of August 31, 2023. The effect size of odds ratio (OR), regression coefficient (β), and 95% confidence interval (CI) were pooled. Heterogeneity and the possibility of publication bias were assessed by using the Q-statistic and Begg's test, respectively., Result: Among the 17 included papers, the study participants were ≥45 years old. Eleven studies assessed the relationship between solid fuels use and cognitive function decline [number of studies (n) = 11, β = -0.144; I 2  = 97.7%]. Five studies assessed the relationship between solid fuels use and cognitive disorders (n = 5, OR = 1.229; I 2  = 41.1%). Switching from using solid fuels to clean fuels could reduce the risk of cognitive function decline as compared to those who remained on using solid fuels (n = 2; β = 0.710; I 2  = 82.4%). Among participants using solid fuels, who cooked without on ventilated stoves were correlated with an enhanced risk of cognitive disorders as compared to participants who cooked with ventilated stoves (n = 2; OR = 1.358; I 2  = 44.7%)., Conclusion: Our meta-analysis showed a negative relationship between solid fuels use with cognitive function, and a positive relationship with cognitive disorders. Cleaner fuels, using ventilation, improved cookstoves can reduce the adverse health hazards of solid fuels use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cladosporium phlei is a phytopathogenic fungus that produces a pigment called phleichrome. This fungal perylenequinone plays an important role in the production of a photosensitizer that is a necessary component of photodynamic therapy. We applied synthetic biology to produce phleichrome using Saccharomyces cerevisiae., Results: The gene Cppks1, which encodes a non-reducing polyketide synthase (NR-PKS) responsible for the biosynthesis of phleichrome in C. phlei, was cloned into a yeast episomal vector and used to transform S. cerevisiae. In addition, a gene encoding a phosphopantetheinyl transferase (PPTase) of Aspergillus nidulans was cloned into a yeast integrative vector and also introduced into S. cerevisiae for the enzymatic activation of the protein product of Cppks1. Co-transformed yeasts were screened on a leucine/uracil-deficient selective medium and the presence of both integrative as well as episomal recombinant plasmids in the yeast were confirmed by colony PCR. The episomal vector for Cppks1 expression was so dramatically unstable during cultivation that most cells lost their episomal vector rapidly in nonselective media. This loss was also observed to a less degree in selective media. This data strongly suggests that the presence of the Cppks1 gene exerts a significant detrimental effect on the growth of transformed yeast cells and that selection pressure is required to maintain the Cppks1-expressing vector. The co-transformants on the selective medium showed the distinctive changes in pigmentation after a period of prolonged cultivation at 20 °C and 25 °C, but not at 30 °C. Furthermore, thin layer chromatography (TLC) revealed the presence of a spot corresponding with the purified phleichrome in the extract from the cells of the co-transformants. Liquid chromatography (LC/MS/MS) verified that the newly expressed pigment was indeed phleichrome., Conclusion: Our results indicate that metabolic engineering by multiple gene expression is possible and capable of producing fungal pigment phleichrome in S. cerevisiae. This result adds to our understanding of the characteristics of fungal PKS genes, which exhibit complex structures and diverse biological activities., (© 2024. The Author(s).)

Tomatoes contain many secondary metabolites such as β -carotene, lycopene, phenols, flavonoids, and vitamin C, which are responsible for antioxidant activity. SlSGR1 encodes a STAY-GREEN protein that plays a critical role in the regulation of chlorophyll degradation in tomato leaves and fruits. Therefore, the present study was conducted to evaluate the sgr1 null lines based on their physicochemical characteristics, the content of secondary metabolites, and the γ -Aminobutyric acid (GABA) content. The total soluble solids (TSS), titrated acidity (TA), and brix acid ratio (BAR) of the sgr1 null lines were higher than those of the wild type(WT). Additionally, the sgr1 null lines accumulated higher levels of flavor-inducing ascorbic acid and total carotenoids compared to WT. Also, the total phenolic content, total flavonoids, GABA content, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical content of the sgr1 null lines were higher than those of the WT. Therefore, these studies suggest that the knockout of the SGR1 gene by the CRISPR/Cas9 system can improve various functional compounds in tomato fruit, thereby satisfying the antioxidant properties required by consumers.

The degradation of farmland in China underscores the need for developing and utilizing saline-alkali soil. Soil health relies on microbial activity, which aids in the restoration of the land's ecosystem, and hence it is important to understand microbial diversity. In the present study, two Gram-stain-positive strains HR 1-10 T and J-A-003 T were isolated from saline-alkali soil. Preliminary analysis suggested that these strains could be a novel species. Therefore, the taxonomic positions of these strains were evaluated using polyphasic analysis. Phylogenetic and 16S rRNA gene sequence analysis indicated that these strains should be assigned to the genus Halalkalibacter . Cell wall contained meso -2,6-diaminopimelic acid. The polar lipids present in both strains were diphosphatidyl-glycerol, phosphatidylglycerol, and an unidentified phospholipid. The major fatty acids (>10%) were anteiso-C 15:0 , C 16:0 and iso-C 15:0 . Average nucleotide identity and digital DNA#x2013;DNA hybridization values were below the threshold values (95% and 70%, respectively) for species delineation. Based on the above results, the strains represent two novel species of the genus Halalkalibacter , for which the names Halalkalibacter flavus sp. nov., and Halalkalibacter lacteus sp. nov., are proposed. The type strains are HR 1-10 T (=GDMCC 1.2946 T = MCCC 1K08312 T = JCM 36285 T ), and J-A-003 T (=GDMCC 1.2949 T = MCCC 1K08417 T = JCM 36286 T ).

Layered 2D transition metal dichalcogenides (TMDs) have been suggested as efficient substitutes for Pt-group metal electrocatalysts in the hydrogen evolution reaction (HER). However, poor catalytic activities in neutral and alkaline electrolytes considerably hinder their practical applications. Furthermore, the weak adhesion between TMDs and electrodes often impedes long-term durability and thus requires a binder. Here, a universal platform is reported for robust dual-atom doped 2D electrocatalysts with superior HER performance over a wide pH range media. V:Co-ReS 2 on a wafer scale is directly grown on oxidized Ti foil by a liquid-phase precursor-assisted approach and subsequently used as highly efficient electrocatalysts. The catalytic performance surpasses that of Pt group metals in a high current regime (≥ 100 mA cm -2 ) at pH ≥ 7, with a high durability of more than 70 h in all media at 200 mA cm -2 . First-principles calculations reveal that V:Co dual doping in ReS 2 significantly reduces the water dissociation barrier and simultaneously enables the material to achieve the thermoneutral Gibbs free energy for hydrogen adsorption., (© 2023 Wiley‐VCH GmbH.)

Background: Potential effect of greenspace exposure on human microbiota have been explored by a number of observational and interventional studies, but the results remained mixed. We comprehensively synthesized these studies by performing a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Methods: Comprehensive literature searches in three international databases (PubMed, Embase, and Web of Science) and three Chinese databases (China National Knowledge Infrastructure, Wanfang, and China Biology Medicine disc) were conducted from inception to November 1, 2023. Observational and interventional studies that evaluated associations between greenspace exposure and human microbiota at different anatomical sites were included. Studies were assessed using the National Toxicology Program's office of Health Assessment and Translation risk of bias tool and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. Two authors independently performed study selection, data extraction, and risk of bias assessment, and evidence grading. Study results were synthesized descriptively., Results: Twenty studies, including 11 observational studies and 9 interventional studies, were finally included into the systematic review. The microbiota of the included studies was from gut (n = 13), skin (n = 10), oral cavity (n = 5), nasal cavity (n = 5) and eyes (n = 1). The majority of studies reported the associations of greenspace exposure with increased diversity (e.g., richness and Shannon index) and/or altered overall composition of human gut (n = 12) and skin microbiota (n = 8), with increases in the relative abundance of probiotics (e.g., Ruminococcaceae) and decreases in the relative abundance of pathogens (e.g., Streptococcus and Escherichia/Shigella). Due to limited number of studies, evidence concerning greenspace and oral, nasal, and ocular microbiota were still inconclusive., Conclusion: The current evidence suggests that greenspace exposure may diversify gut and skin microbiota and alter their composition to healthier profiles. These findings would be helpful in uncovering the potential mechanisms underlying greenspace and human health and in promoting a healthier profile of human microbiota., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The pathogenesis of adult non-cystic fibrosis (CF) bronchiectasis is complex, and the relevant molecular mechanism remains ambiguous. Versican (VCAN) is a key factor in inflammation through interactions with adhesion molecules. This study constructs a stable panoramic map of mRNA, reveals the possible pathogenesis of bronchiectasis, and provides new ideas and methods for bronchiectasis., Methods: Peripheral blood and tissue gene expression data from patients with bronchiectasis and normal control were selected by bioinformatics analysis. The expression of VCAN in peripheral blood and bronchial tissues of bronchiectasis were obtained by transcriptome sequencing. The protein expression levels of VCAN in serums were verified by the enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of VCAN in co-culture of Pseudomonas aeruginosa and bronchial epithelial cells were verified by real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the biological function of VCAN was detected by the transwell assay., Results: The expression of VCAN was upregulated in the bronchiectasis group by sequencing analysis (P < 0.001). The expression of VCAN in the bronchial epithelial cell line BEAS-2B was increased in P. aeruginosa (P.a), which was co-cultured with BEAS-2B cells (P < 0.05). The concentration of VCAN protein in the serum of patients with bronchiectasis was higher than that in the normal control group (P < 0.05). Transwell experiments showed that exogenous VCAN protein induced the migration of neutrophils (P < 0.0001)., Conclusions: Our findings indicate that VCAN may be involved in the development of bronchiectasis by increasing the migration of neutrophils and play an important role in bronchial pathogenesis., (© 2024. The Author(s).)

Introduction: Current U.S./Canadian guidelines recommend hip fracture surgery within 48 h of injury to decrease morbidity/mortality. Multiple studies have identified medical optimization as the key component of time to surgery, but have inherent bias as patients with multiple co-morbidities often take longer to optimize. This study aimed to evaluate time from medical optimization to surgery (TMOS) to determine if "real surgical delay" is associated with: 1) mortality and 2) complications for geriatric hip fracture patients., Methods: A retrospective chart review of geriatric hip fractures treated from 2015-2018 at a single, level-1 trauma center was conducted. Univariate logistic regression was performed to identify association between TMOS and post-operative complication rates. For mortality, the Wilcoxon test was used to compare TMOS for patients discharged following surgery to those who were not., Results: A total of 884 hip fractures were treated operatively, with median TMOS 16.2 h (5.0-22.5, 1st-3rd quartiles). Univariate logistic regression models did not identify an association between TMOS and complication rates. For patients successfully discharged, median TMOS was 16.2 h (5.0-22.3, 1st-3rd quartiles). For the cohort of patients not successfully discharged, median TMOS was 19.1 h (10.1-25.9, 1st-3rd quartiles, p = 0.16)., Conclusion: "Real surgical delay", or TMOS is not associated with increased complications or with inpatient mortality for geriatric hip fracture patients. With few exceptions, our institution adhered to the 48-hour time window from injury to hip surgery. We maintain the belief timely surgery following optimization plays a crucial role in the geriatric hip fracture patient outcomes., Competing Interests: Declaration of competing interest No authors have any relevant conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: To investigate the effect of androgen deprivation therapy (ADT) on health-related quality of life (HRQOL) in Asian men with all stages of prostate cancer., Materials and Methods: READT (real-life evaluation of the effect of ADT in prostate cancer patients in Asia) was a multi-center, prospective observational study involving six sites across four Asian populations. We enrolled eligible prostate cancer patients, who opted for ADT alone or in combination without prior neoadjuvant or adjuvant ADT within 12 months. The EuroQoL-5 dimensions, 5 level scale (EQ-5D-5L) utility index scores and visual analog scale (VAS) were evaluated at baseline, month 6 and month 12., Results: A total of 504 patients were recruited into READT between September 2016 and May 2020 with 52.9% diagnosed with metastatic prostate cancer. The EQ-5D-5L was evaluable in 442/504 (87.7%) of patients. Overall baseline EQ-5D-5L utility index score was 0.924 (interquartile range [IQR] 0.876-1.000). We observed a statistically significant difference in baseline EQ-5D-5L utility index score among different populations with a median EQ-5D-5L utility index score of 1 for Taiwan & Hong Kong, 0.897 for China and 0.838 for Malaysia. Similar trend was observed throughout multiple treatment time-points. Stage IV prostate cancer were significantly associated with a lower baseline EQ-5D-5L utility index score compared to stage I-III prostate cancer, producing a median disutility value of -0.080. Participants had a high median VAS (80, IQR 70-90), indicating good overall health on average during ADT initiation., Conclusions: The study highlights the differences in health state utility index scores among various Asian prostate cancer patients receiving ADT at real-world setting. Our findings will be informative and useful in cost-effectiveness evaluation and policy decision making., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

N 6 -Methyladenosine (6mA) is a well-known prokaryotic DNA modification that has been shown to play epigenetic roles in eukaryotic DNA. Accurate detection and quantification of 6mA are prerequisites for molecular understanding of the impact of 6mA modification on DNA. However, the existing methods have several problems, such as high false-positive rate, time-consuming and complex operating procedures. Chemical sensors for the selective detection of 6mA modification are rarely reported in the literature. Fluorinated phenylboronic acid combined with 19 F NMR analysis is an effective method for determining DNA or RNA modification. In this study, we presented a simple and fast chemical method for labelling the 6th imino group of 6mA using a boric-acid-derived probe. Besides, the trifluoromethyl group of trifluoromethyl phenylboronic acid (2a) could detect 6mA modification through 19 F NMR. Combined with this sensor system, 6mA modification could be detected well and quickly in 6 types of deoxynucleoside mixtures and DNA samples. Taken together, the method developed in the current study has potential for specific detection of 6mA in biological samples.

Pylorus-preserving gastrectomy (PPG) has been widely accepted as a function-preserving gastrectomy for middle-third early gastric cancer (EGC) with a distal tumor border at least 4 cm proximal to the pylorus. The procedure essentially preserves the function of the pyloric sphincter, which requires to preserve the upper third of the stomach and a pyloric cuff at least 2.5 cm. The suprapyloric and infrapyloric vessels are usually preserved, as are the hepatic and pyloric branches of the vagus nerve. Compared with distal gastrectomy, PPG has significant advantages in preventing dumping syndrome, body weight loss and bile reflux gastritis. The postoperative complications after PPG have reached an acceptable level. PPG can be considered a safe, effective, and superior choice in EGC, and is expected to be extensively performed in the future., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The expression levels of SHANK3 are associated with autism spectrum disorder (ASD). The dynamic changes in SHANK3 expression during different stages of brain development may impact the progression of ASD. However, no studies or detailed analyses exploring the upstream mechanisms that regulate SHANK3 expression have been reported. In this study, we employed immunofluorescence to examine the expression of SHANK3 in brain organoids at various stages. Our results revealed elevated levels of SHANK3 expression in brain-like organoids at Day 60. Additionally, we utilized bioinformatics software to predict and analyze the SHANK3 gene's transcription start site. Through the dual luciferase reporter gene technique, we identified core transcription elements within the SHANK3 promoter. Site-directed mutations were used to identify specific transcription sites of SHANK3. To determine the physical binding of potential transcription factors to the SHANK3 promoter, we employed electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). Our findings demonstrated that the transcription factor EGR1 regulates SHANK3 expression by binding to the transcription site of the SHANK3 promoter. Although this study did not investigate the pathological phenotypes of human brain organoids or animal model brains with EGR1 deficiency, which could potentially substantiate the findings observed for SHANK3 mutants, our findings provide valuable insights into the relationship between the transcription factor, EGR1, and SHANK3. This study contributes to the molecular understanding of ASD and offers potential foundations for precise targeted therapy., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified., Methods: In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied in clinical cohort. Multiple pre-clinical models with ECM manipulation were used to evaluate cirrhotic-ECM's effect on ICI treatment. In silico, flow cytometry and IHC were applied to explore how cirrhotic-ECM affect HCC microenvironment. In vitro and in vivo experiments were carried out to identify the mechanism of how cirrhotic-ECM undermined ICI treatment., Results: We defined "a pro-tumor cirrhotic-ECM" which was featured as the up-regulation of collagen type 1 (Col1). Cirrhotic-ECM/Col1 was closely related to impaired T cell function and limited anti PD-1 (aPD-1) response of HCC patients from the TCGA pan cancer cohort and the authors' institution, as well as in multiple pre-clinical models. Mechanically, cirrhotic-ECM/Col1 orchestrated an immunosuppressive microenvironment (TME) by triggering Col1-DDR1-NFκB-CXCL8 axis, which initiated neutrophil extracellular traps (NETs) formation to shield HCC cells from attacking T cells and impede approaching T cells. Nilotinib, an inhibitor of DDR1, reversed the neutrophils/NETs dominant TME and efficiently enhanced the response of HCC to aPD-1., Conclusions: Cirrhotic-ECM modulated a NETs enriched TME in HCC, produced an immune suppressive TME and weakened ICI efficiency. Col1 receptor DDR1 could be a potential target synergically used with ICI to overcome ECM mediated ICI resistance. These provide a mechanical insight and novel strategy to overcome the ICI resistance of HCC., (© 2024. The Author(s).)

High fecundity is a common characteristic of insect pests which increases the difficulty of population control. Serine/threonine kinase Akt is an indispensable component of the insulin signaling pathway. Silencing of LsAkt severely hinders reproduction in Lasioderma serricorne, a stored product insect pest. However, the post-transcriptional pathway of LsAkt in L. serricorne remains unknown. This study identified 2 binding sites of miR-9c-5p and novel-mir50 in the coding sequences of LsAkt. The expression profiles of 2 microRNAs (miRNAs) and LsAkt displayed an opposite pattern during the adult stages. Luciferase reporter assay showed that novel-mir50 and miR-9c-5p could downregulate the expression of LsAkt. Overexpression of miR-9c-5p and novel-mir50 by injection of mimics inhibited the expression of LsAkt and reduced oviposition, decreased egg hatchability, and blocked ovarian development. It also decreased the expression of genes involved in ovarian development (LsVg and LsVgR) and the nutritional signaling pathway (LsTOR, LsS6K, and Ls4EBP), and reduced the phosphorylation of Akt. Conversely, injection of miR-9c-5p and novel-mir50 inhibitors induced the expressions of LsAkt, LsVg, LsVgR, LsTOR, LsS6K, and Ls4EBP, enhanced Akt phosphorylation level, and accelerated ovarian development. Injection of bovine insulin downregulated the expression of miR-9c-5p and novel-mir50 and upregulated the LsAkt expression. It also rescued the reproductive development defects associated with miR-9c-5p/novel-mir50 overexpression, forming a positive regulatory loop of insulin signaling. These results indicate that miR-9c-5p/novel-mir50 regulates the female reproduction of L. serricorne by targeting Akt in response to insulin signaling. The data also demonstrate the effects of the insulin/miRNA/Akt regulatory axis in insect reproduction., (© 2023 Institute of Zoology, Chinese Academy of Sciences.)

The purpose of this retrospective study is to compare the efficacy and safety of the centrifugal separation therapeutic plasma exchange (TPE) using citrate anticoagulant (cTPEc) with membrane separation TPE using heparin anticoagulant (mTPEh) in liver failure patients. The patients treated by cTPEc were defined as cTPEc group and those treated by mTPEh were defined as mTPEh group, respectively. Clinical characteristics were compared between the two groups. Survival analyses of two groups and subgroups classified by the model for end-stage liver disease (MELD) score were performed by Kaplan-Meier method and were compared by the log-rank test. In this study, there were 51 patients in cTPEc group and 18 patients in mTPEh group, respectively. The overall 28-day survival rate was 76% (39/51) in cTPEc group and 61% (11/18) in mTPEh group (P > .05). The 90-day survival rate was 69% (35/51) in cTPEc group and 50% (9/18) in mTPEh group (P > .05). MELD score = 30 was the best cut-off value to predict the prognosis of patients with liver failure treated with TPE, in mTPEh group as well as cTPEc group. The median of total calcium/ionized calcium ratio (2.84, range from 2.20 to 3.71) after cTPEc was significantly higher than the ratio (1.97, range from 1.73 to 3.19) before cTPEc (P < .001). However, there was no significant difference between the mean concentrations of total calcium before cTPEc and at 48 h after cTPEc. Our study concludes that there was no statistically significant difference in survival rate and complications between cTPEc and mTPEh groups. The liver failure patients tolerated cTPEc treatment via peripheral vascular access with the prognosis similar to mTPEh. The prognosis in patients with MELD score < 30 was better than in patients with MELD score ≥ 30 in both groups. In this study, the patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) treated with cTPEc tolerated the TPE frequency of every other day without significant clinical adverse event of hypocalcemia with similar outcomes to the mTPEh treatment. For liver failure patients treated with cTPEc, close clinical observation and monitoring ionized calcium are necessary to ensure the patients' safety., (© 2023 The Authors. Journal of Clinical Apheresis published by Wiley Periodicals LLC.)

Monolayered transition-metal dichalcogenides (TMDs) are easily exposed to air, and their crystal quality can often be degraded via oxidation, leading to poor electronic and optical device performance. The degradation becomes more severe in the presence of defects, grain boundaries, and residues. Here, we report crack propagation in pristine TMD monolayers grown by chemical vapor deposition under ambient conditions and light illumination. Under a high relative humidity (RH) of ∼60% and white light illumination, the cracks appear randomly. Photo-oxidative cracks gradually propagated along the grain boundaries of the TMD monolayers. In contrast, under low RH conditions of ∼2%, cracks were scarcely observed. Crack propagation is predominantly attributed to the accumulation of water underneath the TMD monolayers, which is preferentially absorbed by hygroscopic alkali metal-based precursor residues. Crack propagation is further accelerated by the cyclic process of photo-oxidation in a basic medium, leading to localized tensile strain. We also found that such crack propagation is prevented after the removal of alkali metals via the transfer of the sample to other substrates.