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Quan-Quan Zhuang,1 Zhi-Hang Lin,1 Yan-Cheng Jiang,1 Hao-Hua Deng,2 Shao-Bin He,1,3 Li-Ting Su,4 Xiao-Qiong Shi,2 Wei Chen2 1Department of Pharmacy, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, 2Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 3Department of Pharmacy, Quanzhou Infectious Disease Hospital, 4Department of Pharmaceutical Analysis, Quanzhou Medical College, Quanzhou, People’s Republic of China Abstract: Dendrite-like cobalt selenide nanostructures were synthesized from cobalt and selenium powder precursors by a solvothermal method in anhydrous ethylenediamine. The as-prepared nanocrystalline cobalt selenide was found to possess peroxidase-like activity that could catalyze the reaction of peroxidase substrates in the presence of H2O2. A spectrophotometric method for uric acid (UA) determination was developed based on the nanocrystalline cobalt selenide-catalyzed coupling reaction between N-ethyl-N-(3-sulfopropyl)-3-methylaniline sodium salt and 4-aminoantipyrine (4-AAP) in the presence of H2O2. Under optimum conditions, the absorbance was proportional to the concentration of UA over the range of 2.0–40 µM with a detection limit of 0.5 µM. The applicability of the proposed method has been validated by determination of UA in human serum samples with satisfactory results. Keywords: enzyme mimics, cobalt selenide, peroxidase-like activity, uric acid, human serum

Randi Lynds,1,2,* Chuang Lyu,3,* Gong-Wei Lyu,4 Xie-Qi Shi,1,2 Annika Rosén,5,6 Kamal Mustafa,6 Tie-Jun Sten Shi7 1Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden; 2Division of Oral and Maxillofacial Radiology, Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway; 3State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, 4Department of Neurology, The First Hospital of Harbin Medical University, Harbin, People’s Republic of China; 5Division for Oral and Maxillofacial Surgery, 6Tissue Engineering Group, Department of Clinical Dentistry, Faculty of Medicine and Dentistry, 7Department of Biomedicine, University of Bergen, Bergen, Norway *These authors contributed equally to this work Background: Nerve injury may induce neuropathic pain. In studying the mechanisms of orofacial neuropathic pain, attention has been paid to the plastic changes that occur in the trigeminal ganglia (TGs) and nucleus in response to an injury of the trigeminal nerve branches. Previous studies have explored the impact of sciatic nerve injury on dorsal root ganglia (DRGs) and it has shown dramatic changes in the expression of multiple biomarkers. In large, the changes in biomarker expression in TGs after trigeminal nerve injury are similar to that in DRGs after sciatic nerve injury. However, important differences exist. Therefore, there is a need to study the plasticity of biomarkers in TGs after nerve injury in the context of the development of neuropathic pain-like behaviors. Aim: The aim of this study was to investigate the plasticity of biomarkers associated with chronic persistent pain in TGs after trigeminal nerve injury. Materials and methods: To mimic the chronic nature of the disorder, we used an intraoral procedure to access the infraorbital nerve (ION) and induced a nerve injury in mice. Immunohistochemistry and quantification were used for revealing the expression level of each biomarker in TGs after nerve injury. Results: Two weeks after partial ION injury, immunohistochemistry results showed strongly upregulated expressions of activating transcription factor 3 and neuropeptide Y (NPY) in the ipsilateral TGs. Microglial cells were also activated after nerve injury. In regard to positive neuronal profile counting, however, no significant difference in expression was observed in galanin, substance P, calcitonin gene-related peptide, neuronal nitric oxide synthase, phosphorylated AKT, or P2X3 in ipsilateral TGs when compared to contralateral TGs. Conclusion: In this study, the expression and regulation of biomarkers in TGs have been observed in response to trigeminal nerve injury. Our results suggest that NPY and Iba1 might play crucial roles in the pathogenesis of orofacial neuropathic pain following this type of injury. Further investigations on the relevance of these changes may help to target suitable treatment possibilities for trigeminal neuralgia. Keywords: infraorbital nerve, orofacial pain, sensory neurons, neuropeptides, animal model

Aging is an intricate process involving interactions among multiple factors, which is one of the main risks for chronic diseases, including Alzheimer's disease (AD). As a member of cysteine protease, cathepsin S (CTSS) has been implicated in inflammation across various diseases. Here, we investigated the role of neuronal CTSS in aging and AD started by examining CTSS expression in hippocampus neurons of aging mice and identified a significant increase, which was negatively correlated with recognition abilities. Concurrently, we observed an elevation of CTSS concentration in the serum of elderly people. Transcriptome and fluorescence-activated cell sorting (FACS) results revealed that CTSS overexpression in neurons aggravated brain inflammatory milieu with microglia activation to M1 pro-inflammatory phenotype, activation of chemokine C-X3-C-motif ligand 1 (CX3CL1)-chemokine C-X3-C-motif receptor 1 (CX3CR1) axis and janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway. As CX3CL1 is secreted by neurons and acts on the CX3CR1 in microglia, our results revealed for the first time the role of neuron CTSS in neuron-microglia "crosstalk." Besides, we observed elevated CTSS expression in multiple brain regions of AD patients, including the hippocampus. Utilizing CTSS selective inhibitor, LY3000328, rescued AD-related pathological features in APP/PS1 mice. We further noticed that neuronal CTSS overexpression increased cathepsin B (CTSB) activity, but decreased cathepsin L (CTSL) activity in microglia. Overall, we provide evidence that CTSS can be used as an aging biomarker and plays regulatory roles through modulating neuroinflammation and recognition in aging and AD process., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Objective: To discover the relationship between the RNF213 gene and acute myeloid leukemia (AML), and explore the effect of RNF213 on the proliferation and apoptosis of THP-1 cells., Methods: Analyze the expression of RNF213 gene in AML and its relationship with prognosis through the GEPIA database. Collecting 30 AML patients and non-tumor hematological patients who went to the Affiliated Hospital of Zunyi Medical University from January 2017 to January 2022. RT-qPCR and Western blot were used to detect the expression levels of RNF213 mRNA and protein. Perform survival of patients was analysed by Kaplan-Meier. Meanwhile, the expression levels of RNF213 mRNA and protein were detected in AML cell lines (THP-1, OCI-AML 2 ). CRISPR-Cas9 was used to knockdown the RNF213 gene in THP-1 cells; flow cytometry was used to detect apoptosis rate of cell. CCK-8 and colony formation assay were used to detect cell proliferation. Western blot was used to detect the expression level of Cleaved-Caspase 3 protein., Results: Compared with the control group, the expression level of RNF213 in AML patients was significantly increased, and patients with high expression of RNF213 have a worse prgnosis. Higher expression level of RNF213 protein in THP-1 cells. After knocking down the RNF213 gene of THP-1 cells, cell proliferation was significantly reduced, and the apoptosis rate and expression of apoptosis related protein Cleared-Caspase3 were significantly increased., Conclusion: AML patients have high expression of RNF213 , and the prognosis of high expression patients is poor. The RNF213 gene affects AML cell proliferation and apoptosis, and may be a prognostic marker and potential therapeutic target for AML.

Objective: To elucidate cone-beam computed tomography (CBCT) referral profiles in Western Norway., Materials and Methods: In all, 3,031 referrals to oral- and maxillofacial radiologist were reviewed. Patient data were retrieved retrospectively from electronic charts. The patient's age, gender, and perceived clinical indication were noted, as well as relevant medical and dental history and whether the referring clinician was a general dentist or held a clinical dental specialty., Results: A total of 2,680 referrals fulfilled the inclusion criteria (UiB n = 1,471, and TkVestland, n = 1,209). The female:male ratio was 1,427:1,253. Mean age was 33 years - 35 years for females compared to 31 years for males (p < 0.001). The most common clinical indications were related to impacted teeth (29%), endodontic issues (17%), cleft lip palate (12%), and resorptions (10%). Less common were bone lesions, implant planning, trauma to the teeth or jaws, atypical orofacial pain, and temporo-mandibular joint (TMJ). The patient age-profiles mirrored differences in indications within the cohort. Most referrals were from specialist dentists such as orthodontists, oral surgeons, and endodontists. Interestingly, 543/2,680 (20%) referrals were from general dentists.  Conclusions: Specialist dentists such as orthodontists, oral surgeons, and endodontists refer most patients for clinical indications such as impacted teeth, endodontic issues, and resorptions.

'Zaojiaomi' is a traditional food derived from Gleditsia sinensis or Gleditsia japonica var. delavayi endosperm. However, metabolite profile of Gymnocladus chinensis endosperm and its comparison to the aforementioned species remains understudied. This research employed a UPLC-MS based metabolomics approach to investigate and compare metabolite composition of G. chinensis endosperm with that of G. sinensis and G. japonica endosperm. A total of 1177 metabolites were identified, with 579 and 577 differentially abundant metabolites found between G. chinensis vs. G. japonica and G. chinensis vs. G. sinensis, respectively. They were mainly enriched in pathways related to flavonoid biosynthesis, suggesting potential for enhanced antioxidant activity, compared to G. japonica and G. sinensis. Additionally, G. chinensis endosperm was found to be rich in L-arginine, L-aspartic acid, and zinc elements, which have various health benefits. These findings provide valuable insights into metabolic composition of G. chinensis endosperm and its potential as a functional food source., 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.)

Objectives: The aim of this study was to investigate whether a low-dose cone-beam computed tomography (CBCT) protocol provides diagnostically acceptable image quality for assessing bone healing after alveolar bone grafting., Material and Methods: The study cohort comprised 11 patients (aged 7-14 years) with orofacial clefts who had undergone alveolar bone grafting at Skåne University Hospital in Malmö, Sweden. During the postsurgical follow-up at 6 months, each patient was assessed twice: once with a standard-dose CBCT protocol and once with a low-dose CBCT protocol, which in total corresponds to one CBCT examination made with the exposure settings recommended by the manufacturer. Among others, the assessed parameters included subjective image quality, as well as bone graft height, thickness, and integration., Results: No significant differences were found between the standard- and low-dose protocols for most parameters (p > 0.05). Exceptions included subjective image quality (one observer, p = 0.05) and confidence levels during the assessment (three observers, p = 0.01, 0.01, 0.02)., Conclusions: The low-dose protocol yielded adequate image quality for postoperative CBCT healing assessment in patients who have undergone alveolar bone grafting. However, the confidence level of observers during the assessment with the low-dose protocol was reduced. This study is registered on ClinicalTrials.gov (NCT06395077)., Clinical Trial Registration: This study is registered on ClinicalTrials.gov (NCT06395077)., (© 2024 The Author(s). Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Cobalt has the highest Curie temperature ( T c ) among the elemental ferromagnetic metals and has a hexagonal close-packed (HCP) structure at room temperature. In this study, HCP Co was thinned to the thickness of several ( n ) unit cells along the c -axis and then passivated by halogen atoms, thus being named Co 2 n X 2 (X = F, Cl, Br and I). For Co 2 X 2 and Co 3 X 2 , all of them are not only kinetically but also thermodynamically stable from the viewpoint of the phonon spectra and molecular dynamics. Similar to HCP Co, two-dimensional (2D) Co 2 F 2 , Co 2 Cl 2 and Co 3 X 2 (X = Cl, Br and I) are still ferromagnetic metals within the Stoner model but Co 2 X 2 (X = Br and I) is a ferromagnetic half-metal with the coexistence of the metallic behavior for one spin and the insulating behavior for the other spin. Taking into account the spin-orbital coupling (SOC), the easy-magnetization axis is within the plane where the magnetization is isotropic, making it look like a 2D XY magnet. Applying a critical biaxial strain could lead to an easy-magnetization axis changing from the in-plane to the out-of-plane direction. Finally, we use classical Monte Carlo simulations to estimate the Curie temperature ( T c ) which is as high as 957 and 510 K for Co 2 F 2 and Co 2 Cl 2 , respectively, because of the strong direct exchange interaction. Different from being obtained by mechanical or liquid exfoliation from van der Waals layered structures, our study opens up new possibilities to search for novel 2D ferromagnets from the elemental ferromagnets and provides opportunities for realizing realistic ultra-thin spintronic devices.

Background: Intensive task-oriented training has shown promise in enhancing distal motor function among patients with chronic stroke. A personalized electromyography (EMG)-driven soft robotic hand was developed to assist task-oriented object-manipulation training effectively. Objective. To compare the effectiveness of task-oriented training using the EMG-driven soft robotic hand., Methods: A single-blinded, randomized controlled trial was conducted with 34 chronic stroke survivors. The subjects were randomly assigned to the Hand Task (HT) group (n = 17) or the control (CON) group (n = 17). The HT group received 45 minutes of task-oriented training by manipulating small objects with the robotic hand for 20 sessions, while the CON group received 45 minutes of hand-functional exercises without objects using the same robot. Fugl-Meyer assessment (FMA-UE), Action Research Arm Test (ARAT), Modified Ashworth Score (MAS), Box and Block test (BBT), Maximum Grip Strength, and active range of motion (AROM) of fingers were assessed at baseline, after intervention, and 3 months follow-up. The muscle co-contraction index (CI) was analyzed to evaluate the session-by-session variation of upper limb EMG patterns., Results: The HT group showed more significant improvement in FMA-UE (wrist/hand, shoulder/elbow) compared to the CON group ( P  < .05). At 3-month follow-up, the HT group demonstrated significant improvements in FMA-UE, ARAT, BBT, MAS (finger), and AROMs ( P  < .05). The HT group exhibited a more significant decrease in muscle co-contractions compared to the CON group ( P  < .05)., Conclusions: EMG-driven task-oriented training with the personalized soft robotic hand was a practical approach to improving motor function and muscle coordination., Clinical Trial Registry Name: Soft Robotic Hand System for Stroke Rehabilitation., Clinical Trial Registration-Url: https://clinicaltrials.gov/., Unique Identifier: NCT03286309., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The university encourages knowledge transfer activities, and this robotic hand was licensed by the spin-off company (Hopebotics Limited, Hong Kong SAR, China) in 2021. The authors make every effort to ensure the impartiality, integrity, and scientific rigor of this study. The interpretation of the results and reporting of the findings were conducted objectively and without bias.

Snoring is common in children and is associated with many adverse consequences. One must study the relationships between pharyngeal morphology and snoring physics to understand snoring progression. Although some model studies have provided fluid-structure interaction dynamic descriptions for the correlation between airway size and snoring physics, the descriptions still need to be further investigated in patient-specific airway models. Fluid-structure interaction studies using patient-specific airway structures complement the above model studies. Based on reported cephalometric measurement methods, this study quantified and preset the size of the palatopharynx airway in a patient-specific airway and investigated how the palatopharynx size affects the pharyngeal airflow fluctuation, soft palate vibration, and glossopharynx vibration with the help of a verified FSI method. The results showed that the stenosis anterior airway of the soft palate increased airway resistance and airway resistance fluctuations, which can lead to increased sleep effort and frequent snoring. Widening of the anterior airway can reduce airflow resistance and avoid obstructing the anterior airway by the soft palate vibration. The pharyngeal airflow resistance, mouth inflow proportion, and soft palate apex displacement have components at the same frequencies in all airway models, and the glossopharynx vibration and instantaneous inflow rate have components at the same frequencies, too. The mechanism of this same frequency fluctuation phenomenon can be explained by the fluid-structure interaction dynamics of an ideal coupled model consisting of a flexible plate model and a collapsible tube model. The results of this study demonstrate the potential of FSI in studying snoring physics and clarify to some degree the mechanism of airway morphology affecting airway vibration physics., 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 Ltd. All rights reserved.)

Objectives: To determine pre-operative cleft volume and evaluate cleft´s impact on surrounding anatomical structures in children and adolescents with orofacial clefts using cone bean computed tomography (CBCT) imaging., Methods: The present retrospective study retrieved CBCT examinations of 68 patients from a previous study. The examinations had been exposed either before (n = 53) or after (n = 15) alveolar bone grafting. Pre-operative volume of cleft was determined, and type and location were evaluated. Morphological changes on the adjacent anatomical structures, including the incisive foramen, the nasal septum and floor, and the inferior turbinate, were assessed., Results: Mean bilateral cleft volume was 0.76 cm 3 , while mean unilateral cleft volume was 1.08 cm 3 ; the difference was significant (p < 0.001). Variation in cleft volume, however, was large. The incisive foramen was not visible in the majority of cases with bilateral clefts (71%); the difference was significant (p = 0.001). In cases with unilateral clefts, the nasal septum in 87% was curved towards the cleft or graft side. Also, the mean size of the widest part of the inferior turbinate was 8.8 mm on the cleft or graft side and 10.4 mm on the non-cleft side. The difference was significant (p < 0.001)., Conclusions: When required, CBCT is a feasible method for quantitatively illustrating alveolar clefts and their impact on the morphological development of surrounding structures. Variation in cleft volume was large., (© 2024. The Author(s).)

Background: Children born with an alveolar cleft receive bone grafts for improved function and aesthetics. The cleft area is examined radiologically before and after bone graft. Optimizing radiographic examination protocols is essential to protect these patients from possible delayed radiation injury later in life. This study investigates whether image quality of cone-beam computed tomography (CBCT) exposed with an ultra-low-dose (ULD) protocol is comparable to the clinical default protocol, the standard dose (SD) protocol, in visualizing details of importance in bone grafting of alveolar clefts., Methods: In this randomized controlled study, 72 patients with unilateral or bilateral alveolar clefts between 9 and 19 years (mean age, 9.5 years) were randomized 1:1 with either a ULD or an SD CBCT examination protocol. The CBCT scans were conducted with a Planmeca ProMax Mid scanner with an 8 × 5-cm field of view. Two experienced radiologists blindly evaluated the images and visibility of cortical bone border, trabecular bone, tooth anatomy, root development, periodontal space, and cleft width. The visibility was categorized as unacceptable, acceptable, or excellent., Results: Mann-Whitney U test showed no significant differences in structure visibility between ULD and SD protocols regarding anatomical structures of interest: cortical bone border ( P = 0.07), trabecular bone ( P = 0.64), tooth anatomy ( P = 0.09), root development ( P = 0.57), periodontal space ( P = 0.38), and cleft width ( P = 0.44)., Conclusions: ULD and standard CBCT protocols provide comparable image quality in terms of structure visibility in the examination of alveolar clefts. The ULD protocol is preferred to the SD protocol because of the lower radiation dose without compromising diagnostic information of CBCT images., Clinical Question/level of Evidence: Diagnostic, I., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Gleditsia sinensis , commonly known as Chinese Zaojiao, has important economic value and medicinal compounds in its fruits and thorns, making it widely cultivated artificially in China. However, the available literature on the impact of waterlogging on the growth of G. sinensis seedlings and the accumulation of metabolite compounds in its thorns is limited. To address this knowledge gap, G. sinensis seedlings were planted in soil supplemented with pindstrup substrate, which enhances the water-holding capacity of the soil. The analyses of morphological traits and nutrient elements in one-year-old G. sinensis seedlings grown naturally under ambient conditions and metabolite accumulation in its thorns were conducted. The results showed that the waterlogged soil significantly diminished the height, fresh weight, and dry weight of seedling roots and stems ( P  < 0.05). Furthermore, waterlogging hindered the uptake of iron (Fe) and manganese (Mn), as well as the transport of potassium (K). The identified metabolites within the thorns were categorized into 16 distinct groups. Relative to the control soil, fatty acids and derivatives were the most down-regulated metabolites in the waterlogged soil, accounting for 40.58% of the total metabolites, followed by lignans (38.71%), phenolic acids (34.48%), saccharides and alcohols (34.15%), steroids (16.67%), alkaloids (12.24%), flavonoids (9.28%), and glycerophospholipids (7.41%). Conversely, nucleotides and derivatives experienced the greatest up-regulation in the waterlogged soil, accounting for 50.00% of the total metabolites. In conclusion, waterlogging negatively impacted the growth of G. sinensis seedlings and inhibited the accumulation of metabolites. Hence, when considering the accumulation of secondary metabolites such as lignans and phenolic acids, appropriate management of soil moisture levels should be taken into account., Competing Interests: The authors declare there are no competing interests., (©2024 Luo et al.)

rs2736098 is a synonymous polymorphism in TERT (telomerase reverse transcriptase), an enzyme involved in tumor onset of multiple tissues, and should play no roles in carcinogenesis. However, a search in cancer somatic mutation database indicated that the mutation frequency at rs2736098 is much higher than the average one for TERT . Moreover, there are significant H3K4me1 and H3K27Ac signals, two universal histone modifications for active enhancers, surrounding rs2736098. Therefore, we hypothesized that rs2736098 might be within an enhancer region, regulate TERT expression and influence cancer risk. Through luciferase assay, it was verified that the enhancer activity of rs2736098C allele is significantly higher than that of T in multiple tissues. Transfection of plasmids containing TERT coding region with two different alleles indicated that rs2736098C allele can induce a significantly higher TERT expression than T. By chromatin immunoprecipitation, it was observed that the fragment spanning rs2736098 can interact with USF1 (upstream transcription factor 1). The two alleles of rs2736098 present evidently different binding affinity with nuclear proteins. Database and literature search indicated that rs2736098 is significantly associated with carcinogenesis in multiple tissues and count of multiple cell types. All these facts indicated that rs2736098 is also an oncogenic polymorphism and plays important role in cell proliferation., Competing Interests: 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., (© 2024 The Authors.)

Background: The etiology of unexplained epilepsy in most patients remains unclear. Variants of FRMPD4 are suggested to be associated with neurodevelopmental disorders. Therefore, we screened for disease-causing FRMPD4 variants in patients with epilepsy., Methods: Trios-based whole-exome sequencing was conducted on a cohort of 85 patients with unexplained epilepsy, their parents, and extended family members. Additional cases with FRMPD4 variants were identified from the China Epilepsy Gene Matching Platform V.1.0. The frequency of variants was analyzed, and their subregional effects were predicted using in silico tools. The genotype-phenotype correlation of the newly defined causative genes and protein stability were analyzed using I-Mutant V.3.0 and Grantham scores., Results: Two novel missense variants of FRMPD4 were identified in two families. Using the gene matching platform, we identified three additional novel missense variants. These variants presented at low or no allele frequencies in the gnomAD database. All the variants were located outside the three FRMPD4 main domains (WW, PDZ, and FERM). In silico analyses revealed that the variants were damaging and were predicted to be the least stable. All patients eventually became seizure-free. Eight of the 21 patients with FRMPD4 variants had epilepsy, of which five (63%) had missense variants located outside the domains, two had deletions involving exon 2, and one had a frameshift variant located outside the domains. Patients with epilepsy caused by missense variants were often free of intellectual disabilities (4/5), whereas patients with epilepsy caused by truncated variants had intellectual disabilities and structural brain abnormalities (3/3)., Conclusions: The FRMPD4 gene is potentially associated with epilepsy. The genotype-phenotype correlation of FRMPD4 variants indicated that differences in variant types and locations of FRMPD4 may explain their phenotypic variation., Competing Interests: Declaration of Competing Interest The authors report no competing interests., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Introduction: Prostate cancer is one of the most common cancer types in males and rs12621278:A > G has been suggested to be associated with this disease by previous genome-wide association studies. One thousand genomes project data analysis indicated that rs12621278:A > G is within two long-core haplotypes. However, the origin, causal variant(s), and molecular function of these haplotypes were remaining unclear., Materials and Methods: Population genetics analysis and functional genomics work was performed for this locus., Results: Phylogeny analysis verified that the rare haplotype is derived from Neanderthal introgression. Genome annotation suggested that three genetic variants in the core haplotypes, rs116108611:G > A, rs139972066:AAAAAAAA > AAAAAAAAA, and rs3835124:ATTTATT > ATT, are located in functional regions. Luciferase assay indicated that rs139972066:AAAAAAAA > AAAAAAAAA and rs116108611:G > A are not able to alter ITGA6 (integrin alpha 6) and ITGA6 antisense RNA 1 expression, respectively. In contrast, rs3835124:ATTTATT > ATT can significantly influence PDK1 (pyruvate dehydrogenase kinase 1) expression, which was verified by expression quantitative trait locus analysis. This genetic variant can alter transcription factor cut like homeobox 1 interaction efficiency. The introgressed haplotype was observed to be subject to positive selection in East Asian populations. The molecular function of the haplotype suggested that Neanderthal should be with lower PDK1 expression and further different energy homeostasis from modern human., Conclusion: This study provided new insight into the contribution of Neanderthal introgression to human phenotypes., (© 2023 University College London (UCL) and John Wiley & Sons Ltd.)

Purpose: The TRAK1 gene is mapped to chromosome 3p22.1 and encodes trafficking protein kinesin binding 1. The aim of this study was to investigate the genotype-phenotype of TRAK1 -associated epilepsy., Methods: Trio-based whole-exome sequencing was performed on a cohort of 98 patients with epilepsy of unknown etiologies. Protein modeling and the VarCards database were used to predict the damaging effects of the variants. Detailed neurological phenotypes of all patients with epilepsy having TRAK1 variants were analyzed to assess the genotype-phenotype correlations., Results: A novel TRAK1 compound heterozygous variant comprising variant c.835C > T, p.Arg279Cys and variant c.2560A > C, p.Lys854Gln was identified in one pediatric patient. Protein modeling and VarCards database analyses revealed that the variants were damaging. The patient received a diagnosis of early infantile epileptic spasms with a developmental disorder; he became seizure-free through valproate and adrenocorticotropic hormone treatment. Further results for six variants in 12 patients with epilepsy indicated that biallelic TRAK1 variants (including homozygous or compound heterozygous variants) were associated with epilepsy with developmental disorders. Among these patients, eight (67%) had epileptic spasms and seven (58%) were intractable to anti-seizure medicines. Moreover, eight patients experienced refractory status epilepticus, of which seven (88%) died in early life. To our knowledge, this is the first reported case of epilepsy caused by TRAK1 compound heterozygous variants., Conclusion: Biallelic TRAK1 variants can cause epilepsy and developmental disorders. In these patients, seizures progress to status epilepticus, suggesting a high risk for poor outcomes and the requirement of early treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Xiong, Pan, Lei, Shu, Shi and Tian.)

Background: Observational studies have suggested a possible association between hypothyroidism and increased risk of ischemic stroke. However, a causal relationship remains unclear., Methods: Data on single nucleotide polymorphisms (SNPs) associated with hypothyroidism and ischemic stroke were sourced from the FinnGens database and the UK Biobank of European descent. Both databases underwent separate two-sample Mendelian randomization (MR) analyses. A subsequent meta-analysis of MR results using a random-effects model was conducted to determine the causal relationship between hypothyroidism and ischemic stroke., Results: All five analyses indicated a positive causal relationship between hypothyroidism and ischemic stroke. MR analysis of the association between hypothyroidism and ischemic stroke yielded a result of the inverse variance weighted (IVW) method at 4.7411 (1.3598-16.5308), p  = 0.0146. The analysis of ischemic stroke (without excluding controls) yielded a result of the IVW method of 4.5713 (1.3570-15.3986), p  = 0.0142. MR analysis with cerebral infarction yielded a result of the IVW method at 1.0110 (1.0006-1.0215), p  = 0.0373. The MR analysis with cerebrovascular disease sequelae yielded an IVW method result of 2.4556 (1.0291-5.8595), p  = 0.0429. Analysis for the sequelae of cerebrovascular disease (without excluding controls) yielded an IVW method result of 2.4217 (1.0217-5.7402), p  = 0.0446. No evidence of heterogeneity or horizontal pleiotropy was found. The meta-analysis of the five MR results was 2.24 (1.18-4.26), p  = 0.025., Conclusion: Our two-sample Mendelian randomization study suggested a causal relationship between hypothyroidism and ischemic stroke, indicating that hypothyroidism could be a risk factor for ischemic stroke. However, further studies are required to elucidate the underlying biological mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Shi, Shui, Liu, Bu, Liu and Yin.)

Alpine Rhododendron species are prominent constituents and renowned ornamental plants in alpine ecosystems. Consequently, evaluating the genetic variation in embolism resistance within the genus Rhododendron and predicting their adaptability to future climate change is important. Nevertheless, the assessment of embolism resistance in Rhododendron species remains limited. This investigation aimed to examine leaf vulnerability to embolism across ten alpine Rhododendron species, which are frequently employed as ornamental species in Rhododendron forests in Southwest China. The study analyzed the correlation between embolism resistance and various morphological traits, while also conducting water control experiments to evaluate the relationship between embolism resistance and drought resistance. The outcomes indicated pronounced variations in leaf vulnerability to embolism among species, as reflected by the water potential at 50% of embolized pixels (P 50 ). Furthermore, the leaf P 50 exhibited a significant positive correlation with vessel diameter (D) (R 2  = 0.44, P = 0.03) and vessel wall span (b) (R 2  = 0.64, P = 0.005), while displaying a significant negative correlation with vessel reinforcement ((t/b) 2 ) (R 2  = 0.67, P = 0.004). These findings underscore the reliability of selecting species based on embolism vulnerability to preserve the diversity of alpine ecosystems and foster resilience to climate change., (© 2024 Scandinavian Plant Physiology Society.)

Objective: To explore the clinical manifestations, diagnosis, pathological features and treatment of small-cell carcinoma of the prostate (SCCP)., Methods: We conducted a retrospective analysis of the clinical and pathological data of 2 cases of confirmed SCCP treated from November 2017 to March 2018, and reviewed relevant literature., Results: Both the patients had the symptoms of frequent, urgent and difficult urination, with an elevated level of PSA and gradesⅡ－Ⅲ enlargement of the prostate at palpation. One underwent prostate puncture biopsy and the other received transurethral 1470 laser vaporization resection of the tumor. Postoperative pathology indicated prostate adenocarcinoma accompanied by SCCP in both of the cases. One of them was treated by etoposide-platinum (EP) chemotherapy and died of systemic multiple organ failure 20 months after diagnosis, while the other underwent endocrine therapy and has lived with tumor up to the present day., Conclusion: The incidence rate of SCCP is low, its malignancy is high, and its prognosis is poor. The average survival of the patient is about 7 to 10 months after diagnosis. Currently there is no effective management of the dissease, except by relying on the experience of the treatment of small-cell lung cancer, with chemotherapy as the main option.

Objectives: We aimed to map the correlation between thermoluminescent dosimeters (TLDs) and Gafchromic film for measuring absorbed doses and to compare minimum, maximum, and mean absorbed doses over larger regions of interest and at various craniofacial organs and tissues during cone beam computed tomography (CBCT) exposure of the mandibular third molar region., Study Design: We positioned TLDs at 75 measurement points in a head phantom. Gafchromic film was cut to the same shape as the 5 levels of the phantom and was placed on top of the TLDs. Both dosimetry methods thus included the surface of each level simultaneously. CBCT scans were made using a 5 × 5 cm field of view and a rotation angle of 200°. Measurements included absorbed dose distributions, doses at all 75 points, and minimum, maximum, and mean doses within organs and tissues., Results: The correlation of point-dose measurements at all TLD sites with doses measured on film was strong (R 2  = 0.9687), with greatest correlation at lower doses (<2 mGy). Large deviations between TLD and film measurements of minimum and maximum doses and absorbed doses to the organs occurred at all 5 levels. TLD positioning failed to cover several organ sites; for these, only absorbed dose measurements from the film were available., Conclusions: TLDs were unable to sample dose distributions and gradients accurately. The characteristics of Gafchromic LD-V1 film make it a favorable alternative in dental CBCT dosimetry., Competing Interests: Declaration of interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the influential factors of erectile dysfunction (ED) in patients with localized prostate cancer (LPC) after radical surgery., Methods: The clinical data of 150 male patients diagnosed with LPC and normal erectile function (EF) before surgery admitted to the Department of Urology of the Eastern Theatre General Hospital from January 2021 to January 2023 were retrospectively analyzed. The EF status of the patients 6 months after surgery was assessed using the International Erectile Function Index -5(IIEF-5). Age, Gleason score, PSA level, TNM stage, preoperative International prostatic symptom score (IPSS), preoperative prostate volume, smoking index, alcohol consumption index, educational level, comorbidities, operation mode, and psychosexual state were used as influencing factors to analyze their effects on postoperative ED., Results: Of the 150 patients, 88 had ED and 62 had normal EF. Univariate analysis showed that age, preoperative IPSS, preoperative prostate volume, comorbidities and sexual and psychological status were significantly correlated with postoperative ED. Further multivariate logistic regression analysis showed that age, preoperative prostate volume, comorbidities and sexual and psychological status were independent factors influencing the occurrence of ED after RP in LPC patients., Conclusion: The recovery of sexual function of patients with localized prostate cancer after radical surgery is generally poor, and the incidence of ED is high. Its independent influencing factors include age, preoperative prostate volume, comorbidities and sexual psychological state, etc. Correct intervention of different influencing factors is required in clinical work. In order to provide a better diagnosis and treatment scheme for LPC patients undergoing radical treatment, reduce the incidence of postoperative ED and improve the quality of life of patients after surgery.

Objective: To investigate the safety and efficacy of Micro-Percutaneous Nephrolithotomy (Micro-PCNL) combined with flexible ureteroscopic lithotomy (FURL) in the treatment of 1-2 cm symptomatic, refractory lower calyceal stones., Methods: A retrospective analysis was performed concerning the clinical data of 28 patients with 1-2 cm symptomatic, refractory lower calyceal stones. When there was a difficulty in performing FURL in Affiliated Hospital of Hebei University from January 2019 to February 2022, ultrasound-guided F4.8 visual puncture was performed on the lower calyceal stone,with a holmium laser was then used to treat the remaining stones, followed by drainage using a flexible ureteroscopic sheath and postoperative indwelling of the ureteral stent without a nephrostomy tube. The surgery time, intraoperative bleeding and stone-free rate(SFR) were recorded, and the VAS score was used to evaluate the patients' pain status., Results: The surgery was completed successfully in an average of 43.46 ± 10.04 minutes, and the puncture time was 3.46 ± 0.69 minutes. The SFR was 85.71%(24/28) and 92.86%(26/28) at one day and 30 days after surgery, respectively. Two patients with residual stones greater than 0.6 cm in size underwent extracorporeal shock wave lithotripsy four weeks after surgery. Patients were followed up for three months after surgery, and the SFR was revised to 96.43%(27/28). In addition, the VAS scores of all patients decreased significantly from before to after surgery, and the difference was statistically significant(p< 0.05)., Conclusion: Micro-Percutaneous Nephrolithotomy (Micro-PCNL) combined with FURL is safe and effective in the treatment of 1-2 cm symptomatic, refractory lower calyceal stones., Competing Interests: Conflicts of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Objective: To determine the clinical impact of preventive nursing on children with hypospadias and the intervention effect on postoperative complications., Study Design: Comparative study. Place and Duration of the Study: Department of Urology Surgery, Beijing Children's Hospital Affiliated to Capital Medical University Baoding Hospital, Hebei, China, from August 2019 to July 2021., Methodology: Children with hypospadias who received elective surgery were randomly divided into two groups of forty cases each. The control group received traditional specialised nursing care during the perioperative period, the study group administered preventive care on the control basis. The postoperative rehabilitation, VAS, anxiety and depression score, postoperative complications, and nursing satisfaction were compared between the two groups., Results: The time of first bowel movement, extubation, and hospitalisation in the study group were significantly shorter than in the control group, with statistically significant value (p<0.001). After intervention, the SAS and SDS in the study group were significantly lower than those in the control group, and the difference was statistically significant (p<0.05). The incidence of complications in the study group was 7.50%, lower than the 25% of control group (p = 0.034). The postoperative VAS scores of the study group were significantly lower than those of control group at 6 and 24 hours (p<0.05). Besides, nursing satisfaction in the study group was 97.50%, higher than the 82.50% of the control group (p = 0.025)., Conclusion: Preventive nursing had a reliable nursing effect on children undergoing hypospadias surgery, which can reduce postoperative complications, alleviate postoperative pain, improve postoperative anxiety and depression, enhance nursing experience, and promote postoperative recovery., Key Words: Preventive care, Hypospadias in male children, Urethroplasty, Complication, Clinical effect.

Purpose: Pancreatic cancer is one of the most aggressive malignant tumors with poor prognosis. High-intensity focused ultrasound (HIFU) is an effective and safe treatment option for advanced pancreatic cancer, however, the survival time of patients after the treatment was different. So, the purpose of this study was to evaluate the relationship between the high-risk characteristics and prognosis of unresectable pancreatic cancer after HIFU treatment., Patients and Methods: This prospective study included 30 patients with unresectable pancreatic cancer who received HIFU at Beijing Friendship Hospital. Data on patients' tumor size, pain scores, peripheral blood lymphocyte subsets, CA19-9 and contrast enhanced ultrasound (CEUS) features were collected to assess the relationship with overall survival (OS) after HIFU., Results: The median OS from the start of HIFU treatment was 159 days, 95% confidence interval (95% CI): 108-210. The levels of pain were determined by visual analogue scale (VAS) score, and the quartile of the score decreased from 6 (2, 7) to 4 (2, 5) immediately after one session of the treatment (p = 0.001). The diagnostic model showed that high post VAS score and decreasing of peripheral CD4 + T cells were significantly correlated with poor prognosis (p < 0.05), and showed good discrimination ability (AUC = 0.848, 95% CI = 0.709-0.987)., Conclusion: HIFU can effectively relieve pain in patients with unresectable pancreatic cancer. Post treatment VAS and change of peripheral CD4 + T cells are independent risk factors affecting the prognosis in patients with unresectable pancreatic cancer after HIFU treatment., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To compare the efficacy and complications of radical surgery (RP) and radical radiotherapy (RRT)., Methods: The clinical data of patients diagnosed with localized prostate cancer in General Hospital of Eastern Theater Command with RP and RRT from January 2015 to December 2019, Observed and recorded patient preoperative and postoperative PSA levels, biochemical Relapse-free Survival and clinical Relapse-free Survival,and the occurrence of hematuria, urinary incontinence, erectile dysfunction, ankylurethria, diarrhea, hemoproctia and radiocystitis., Results: A total of 150 patients with localized prostate cancer were included in this study, including 105 patients with RP and 45 patients undergoing RRT. There was no significant difference between the complication rates of hematuria, urinary incontinence, erectile dysfunction and ankylurethria(P>0.05).Patients in the RRT group had higher rates of diarrhea(20.00% vs 2.86%), hemoproctia(15.56% vs 1.90%) and radiocystitis(13.33% vs 0%) than those in the RP group, with significant differences (P<0.05). The 5-year bRFS was lower than that in the RP group (95.1% vs 90.7%), with no statistical significance (P=0.832); the 5-year cRFS in the RP group was lower than that in the RRT group (91.2% vs 89.6%), with no significant difference (P=0.971)., Conclusion: The incidence of diarrhea, hemoproctia and radiocystitis was lower in the RP group than in the RRT group, and the recurrence-free survival was not significantly different between the two groups.

Background: The aim of the study was to evaluate the cost-effectiveness of nivolumab plus chemotherapy as first-line treatment for patients with advanced gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma from the perspective of Chinese and US society., Methods: To conduct the analysis, a state-transitioned Markov model, which included three mutually exclusive health states (progression-free survival (PFS), progressive disease (PD), and death), was developed. Cycle length was set at 3 weeks and lifetime horizon was set at 10 years. Costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated in the analysis. Willingness-to-pay (WTP) thresholds in the model were set at $37,653.00/QALY in China and $100,000.00/QALY in the US, respectively. Meanwhile, one-way sensitivity analyses and probabilistic sensitivity analyses were conducted to investigate the robustness of the model., Results: Over a lifetime horizon, the ICERs of nivolumab plus chemotherapy versus chemotherapy alone were $430,185.04/QALY and $944,089.78/QALY in China and the US, respectively. Cost of nivolumab and utility for the PFS state had the most significant impact on ICERs both in the US and China based on the results of the one-way sensitivity analyses. In the probabilistic sensitivity analyses, the proportions of nivolumab plus chemotherapy being cost-effective compared with chemotherapy alone were 0%., Conclusions: In conclusion, nivolumab plus chemotherapy is unlikely to be a cost-effective treatment option compared with chemotherapy alone in the first-line setting of advanced gastric, GEJ, or esophageal adenocarcinoma., (© 2023. BioMed Central Ltd., part of Springer Nature.)

We demonstrate that two-dimensional crystals made of active particles can experience extremely large spontaneous deformations without melting. Using particles mostly interacting via pairwise repulsive forces, we show that such active crystals maintain long-range bond order and algebraically decaying positional order, but with an exponent η not limited by the 1/3 bound given by the (equilibrium) KTHNY theory. We rationalize our findings using linear elastic theory and show the existence of two well-defined effective temperatures quantifying respectively large-scale deformations and bond-order fluctuations. The root of these phenomena lies in the sole time-persistence of the intrinsic axes of particles, and they should thus be observed in many different situations.

Objective: To investigate the clinical effect and safety of transurethral 1470 nm semiconductor laser vaporization and cutting in the treatment of super high age and high risk benign prostatic hyperplasia., Methods: The clinical data of 38 patients with super-high-risk prostate who underwent transurethral surgery in our hospital from April 2016 to December 2017 were retrospectively analyzed. All patients had obvious progressive dysuria. The diagnosis of benign prostatic hyperplasia was confirmed by urinary color Doppler ultrasound, anal finger examination, PSA, prostate biopsy, etc., and prostate cancer was excluded. Each patient was aged ≥85 years old and combined with one or more types. Senile basic diseases such as diabetes, hypertension, coronary heart disease, emphysema, sequelae of cerebral infarction, etc. The patients were randomly divided into two groups. The observation group was treated with transurethral 1470 nm semiconductor laser vaporization and the control group was treated with transurethral plasma electrotomy. To observe the changes of vital signs, bleeding, duration of surgery, postoperative bladder irrigation time, urinary catheter retention time, and changes of hemoglobin before and after surgery. Surgical safety. The international prostate symptom score (IPSS), quality of life score (QoL), maximum urinary flow rate (Qmax), and post-void residual urine volume (PVR) were evaluated 2 months after surgery and compared with preoperative evaluation to evaluate the surgical outcome., Results: All 38 operations were successfully completed.The vital signs of the patients were stable during the operation. The average operation time of the observation group and the control group was (79.6±24.7 vs 69.5±19.8) min, P>0.05. The hemoglobin decreased by (6.9±3.0) g/L vs (13.2±4.0) g/L， after operation.P<0.05; postoperative bladder irrigation time (14.7±2.8 vs 23.5±5.3)h, P<0.05; average postoperative urinary catheter retention time (3.8±0.4 vs 5.7±0.9)d, P<0.05; average postoperative hospital stay (5.3±1.1 vs 7.2±1.9)d, P<0.05; all patients were followed up for 2 months, IPSS, QoL, Qmax, PVR and other indicators were significantly improved compared with preoperative, no major bleeding, urinary incontinence, cardiopulmonary failure and Significant urinary tract irritation symptoms occur., Conclusion: Compared with plasma electric resection, transurethral 1470 nm semiconductor laser treatment of benign prostatic hyperplasia has the advantages of high safety and remarkable effect, especially suitable for patients with high age and high risk.

Objective: To compare and analyze the clinical effects of microscopic surgery and conventional surgery in children with penile hypospadias and the differences in postoperative urodynamic indexes., Methods: It was a clinical comparative study. A total of 80 children with penile hypospadias admitted to Beijing Children's Hospital Affiliated to Capital Medical University Baoding Hospital from July 2018 to September 2022 were selected and randomly divided into two group. The experimental group were treated with microscopic urethroplasty, while the control group were treated with traditional urethroplasty. The operative effect, operation time, total intraoperative blood loss, postoperative hospital stay and incidence of surgical complications were compared and analyzed between the two groups. All the children were followed up for two years, and the changes in urodynamic parameters including maximum urine flow rate (Qmax), average urine flow rate (Qavc), urine flow time (FT), peak time (TQmax) and residual urine (PVR) were compared before, two weeks after, six months after and two years after surgery., Results: The efficacy of the experimental group was significantly higher than that of the control group (p=0.013). The intraoperative blood loss and postoperative hospital stay in the experimental group were significantly better than those in the control group (p=0.000). The incidences of urinary leakage and urethral stricture in the experimental group were lower than those in the control group (p<0.05). The Qmax level in the experimental group was higher than that in the control group at six months and two years after surgery, while the FT level was lower than that of the control group (p<0.05)., Conclusion: Microscopic surgery is a method with significant clinical value in the treatment of penile hypospadias., Competing Interests: Conflicts of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

In recent years, petal blight disease caused by pathogens has become increasingly epidemic in Rhododendron . Breeding disease-resistant rhododendron is considered to be a more environmentally friendly strategy than is the use of chemical reagents. In this study, we aimed to investigate the response mechanisms of rhododendron varieties to petal blight, using transcriptomics and metabolomics analyses. Specifically, we monitored changes in gene expression and metabolite accumulation in Rhododendron 'Xiaotaohong' petals infected with the Alternaria sp. strain (MR-9). The infection of MR-9 led to the development of petal blight and induced significant changes in gene transcription. Differentially expressed genes (DEGs) were predominantly enriched in the plant-pathogen interaction pathway. These DEGs were involved in carrying out stress responses, with genes associated with H 2 O 2 production being up-regulated during the early and late stages of infection. Correspondingly, H 2 O 2 accumulation was detected in the vicinity of the blight lesions. In addition, defense-related genes, including PR and FRK, exhibited significant up-regulated expression during the infection by MR-9. In the late stage of the infection, we also observed significant changes in differentially abundant metabolites (DAMs), including flavonoids, alkaloids, phenols, and terpenes. Notably, the levels of euscaphic acid, ganoderol A, (-)-cinchonidine, and theophylline in infected petals were 21.8, 8.5, 4.5, and 4.3 times higher, respectively, compared to the control. Our results suggest that H 2 O 2 , defense-related genes, and DAM accumulation are involved in the complex response mechanisms of Rhododendron 'Xiaotaohong' petals to MR-9 infection. These insights provide a deeper understanding of the pathogenesis of petal blight disease and may have practical implications for developing disease-resistant rhododendron varieties.

Asthma is a complex disease, often with evident genetic predisposition; for example, the single-nucleotide polymorphism (SNP) rs7130588 was significantly associated with asthma by genome-wide association study (GWAS). Analysis of 1000 Genomes Project data suggests that there is another SNP, rs6592645, in complete linkage disequilibrium with rs7130588 and should present the same signal in GWAS. However, the causal SNP and the mechanism for the association between rs7130588 and asthma remain to be elucidated. In the presents study, results from dual-luciferase assays indicated that the A/G alleles of rs7130588 failed to present significantly different reporter gene expression. By contrast, A allele of rs6592645 presented a significant increase in relative luciferase activity than G allele, thus suggesting that rs6592645 may be a causal SNP. Using chromosome conformation capture, the enhancer region containing rs6592645 was observed to interact with promoter region of leucine-rich repeat-containing 32 ( LRRC32) . Gene expression quantification suggested that LRRC32 expression is significantly increased in lung tissue of patients with asthma and is dependent on the genotype of this locus, thus verifying that LRRC32 may be involved in asthma onset and that rs6592645 can regulate LRRC32 expression. Through chromatin immunoprecipitation, transcription factor 3 (TCF3) was identified to bind to rs6592645 surrounding region and the interaction between TCF3 and rs6592645 surrounding region was investigated. Results from the present study may improve our understanding of the mechanism by which the genetic variation in this locus might influence asthma susceptibility., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

The rational design of the directional charge transfer channel represents an important strategy to finely tune the charge migration and separation in photocatalytic CO 2 -to-fuel conversion. Despite the progress made in crafting high-performance photocatalysts, developing elegant photosystems with precisely modulated interfacial charge transfer feature remains a grand challenge. Here, a facile one-pot method is developed to achieve in situ self-assembly of Pd nanocrystals (NYs) on the transition metal chalcogenide (TMC) substrate with the aid of a non-conjugated insulating polymer, i.e., branched polyethylenimine (bPEI), for photoreduction of CO 2 to syngas (CO/H 2 ). The generic reducing capability of the abundant amine groups grafted on the molecular backbone of bPEI fosters the homogeneous growth of Pd NYs on the TMC framework. Intriguingly, the self-assembled TMCs@bPEI@Pd heterostructure with bi-directional spatial charge transport pathways exhibit significantly boosted photoactivity toward CO 2 -to-syngas conversion under visible light irradiation, wherein bPEI serves as an efficient hole transfer mediator, and simultaneously Pd NYs act as an electron-withdrawing modulator for accelerating spatially vectorial charge separation. Furthermore, in-depth understanding of the in situ formed intermediates during the CO 2 photoreduction process are exquisitely probed. This work provides a quintessential paradigm for in situ construction of multi-component heterojunction photosystem for solar-to-fuel energy conversion., (© 2023 Wiley-VCH GmbH.)

Objective: To explore the safety and effectiveness of the "scarless" circumcision technique (a modified sleeve-style circumcision method) that preserves the original appearance, providing a more suitable surgical option for patients with redundant prepuce., Methods: Clinical data of patients who underwent "scarless" circumcision at the Eastern Theater Command General Hospital from April 2022 to March 2023 were collected, with patients who underwent conventional circumcision (single-use stapler method) during the same period serving as the control group. The two groups were compared in terms of operation time, postoperative recovery time, incidence of postoperative complications, and patient satisfaction rates after surgery., Results: The operation time for the study group was significantly longer than that of the control group; there was no significant difference in pain scores on the day of surgery between the two groups, but the pain scores on postoperative days 1, 3, and 7 were lower in the study group than in the control group; the postoperative recovery time was significantly shorter in the study group than in the control group; regarding postoperative complications: the control group had higher rates of edema, incision infection, and wound dehiscence than the study group. A satisfaction survey conducted 30 days postoperatively showed higher satisfaction in the study group than in the control group., Conclusion: The "scarless" circumcision technique that preserves the original appearance is safe and effective for patients with simple redundant prepuce and is a new surgical method with value for widespread adoption.

Objective: Optimization of radiographic examinations is essential for radiation protection. The objective of the study was to investigate the clinical applicability of a low-dose CBCT protocol as compared to the default for pre-surgical evaluation of mandibular third molars., Material & Methods: Forty-eight patients (62 teeth) referred for pre-surgical mandibular third molar investigation were recruited after justification for CBCT. Two CBCT scans of each site were made using a default protocol and a low-dose protocol (Veraviewepocs 3D F40, J Morita Corp, Kyoto, Japan). The low-dose protocol had the same tube potential (90 kV) and exposure time (9.4 s) as the default, but with reduced tube current, from 5 mA to 2 mA. Four observers evaluated the visibility of five relevant anatomical variables. Image quality was ranked on a 3-point scale as diagnostically acceptable, doubtful, or unacceptable. The Wilcoxon signed-rank test compared differences between the two protocols. The significance level was set at p ≤ .05., Results: No significant differences were found between the two protocols for any observer regarding the visibility of the relationship and proximity between the roots and the mandibular canal; root morphology; and possible root resorption of the second molar. The periodontal ligament differed significantly in visibility between the two protocols ( p ≤ .05)., Conclusions: This study indicates that a low-dose CBCT protocol with a 60% reduction of the tube current provides, in most cases, acceptable image quality for pre-surgical assessment of mandibular third molars. Optimization of CBCT protocols should be a priority according to recommended guidelines.

Purpose: Lung cancer is a malignant tumor with obvious genetic predisposition. Association studies have proposed that rs2853677, a SNP localizing at intron region of TERT (telomerase reverse transcriptase), is significantly associated with TERT expression, telomere length and eventually lung cancer risk. However, functional genomics work indicates that rs2853677 is not with the ability to alter gene expression. All these facts make us hypothesize that some other genetic variation(s) are in linkage disequilibrium (LD) with rs2853677 and influence TERT expression., Methods: LD pattern in rs2853677 nearby region was analyzed based on 1000 genomes data for three representative populations in the world and functional genomics research was performed for this locus., Results: Only one SNP, rs2736099, is in strong LD with rs2853677 in East Asian. Dual-luciferase reporter assay verifies that rs2736099 can regulate gene expression and should be the causal SNP for this disease. Through chromosome conformation capture assay, it is disclosed that the enhancer surrounding rs2736099 can interact with TERT promoter. Through chromatin immunoprecipitation, the transcription factor SP1 (Sp1 transcription factor) is recognized for the chromatin segment spanning rs2736099., Conclusions: Our results provide the missing piece between genetic variation at this locus and lung cancer risk, which is also applied to tumorigenesis in other tissues and cell proliferation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Circumcision is the simplest, most commonly used and most effective treatment for male prepuce overlength, phimosis and other diseases. There has also been a shift from traditional circumcision to simpler, faster, less invasive, instrument-based methods. This paper reviews the surgical methods of circumcision(Traditional circumcision、Electrosurgical circumcision、Laser circumcision、Sleeve circumcision, Dermotomy at the base of penis, Shangring, Gomco, Mogen, PlastiBell, PrePex, Alisklamp and Disposable circumcision suture apparatus), hoping to provide reference for clinicians to choose the appropriate circumcision methods for patients.

Objective: To investigate the clinical efficacy of posterior cervical pedicle screw short-segment internal fixation for the treatment of atlantoaxial fracture and dislocation., Methods: The clinical data of 60 patients with atlantoaxial vertebral fracture and dislocation underwent surgery between January 2015 and January 2018 were retrospectively analyzed. The patients were divided into study group and control group according to different surgical methods. There were 30 patients in study group, including 13 males and 17 females, with an average age of (39.32±2.85) years old, were underwent short-segment internal fixation with posterior cervical pedicle screws. There were 30 patients in control group, including 12 males and 18 females, with an average age of (39.57±2.90) years old, were underwent posterior lamina clip internal fixation of the atlas. The operation time, intraoperative blood loss, postoperative ambulation time, hospitalization time and complications between two groups were recorded and compared. The pain visual analogue scale(VAS), Japanese Orthopedic Association(JOA) score of neurological function, and fusion status were evaluated between two groups., Results: All patients were followed up for at least 12 months. The study group was better than control group in operation time, intraoperative blood loss, postoperative off-bed activity time, and hospital stay ( P =0.000). One case of respiratory tract injury occurred in study group. In control group, 2 cases occurred incision infection, 3 cases occurred respiratory tract injury, and 3 cases occurred adjacent segmental joint degeneration. The incidence of complications in study group was lower than that in control group ( χ 2 =4.705, P =0.030). At 1, 3, 7 days after operation, VAS of study group was lower than that of control group( P =0.000). At 1, 3 months after operation, JOA score of study group was higher than that of control group( P =0.000). At 12 months after operation, all the patients in the study group achieved bony fusion. In control group, there were 3 cases of poor bony fusion and 3 cases of internal fixation fracture, the incidence rate was 20.00%(6/30). The difference between two groups was statistically significant ( χ 2 =4.629, P =0.031)., Conclusion: Posterior cervical short-segment pedicle screw fixation for atlantoaxial fracture and dislocation has the advantages of less trauma, shorter operation time, fewer complications, and less pain, and can promote the recovery of nerve function as soon as possible.

Background: Mycoplasma pneumoniae (MP) is a commonly occurring pathogen causing community-acquired pneumonia (CAP) in children. The global prevalence of macrolide-resistant MP (MRMP) infection, especially in Asian regions, is increasing rapidly. However, the prevalence of MRMP and its clinical significance during the COVID-19 pandemic is not clear., Methods: This study enrolled children with molecularly confirmed macrolide-susceptible MP (MSMP) and MRMP CAP from Beijing Children's Hospital Baoding Hospital, Capital Medical University between August 2021 and July 2022. The clinical characteristics, laboratory findings, chest imaging presentations, and strain genotypes were compared between patients with MSMP and MRMP CAP., Results: A total of 520 hospitalized children with MP-CAP were enrolled in the study, with a macrolide resistance rate of 92.7%. Patients with MRMP infection exhibited more severe clinical manifestations (such as dyspnea and pleural effusion) and had a longer hospital stay than the MSMP group. Furthermore, abnormal blood test results (including increased LDH and D-dimer) were more common in the MRMP group (P<0.05). Multilocus variable-number tandem-repeat analysis (MLVA) was performed on 304 samples based on four loci (Mpn13-16), and M3562 and M4572 were the major types, accounting for 74.0% and 16.8% of the strains, respectively. The macrolide resistance rate of M3562 strains was up to 95.1%., Conclusion: The prevalence of MRMP strains in hospitalized CAP patients was extremely high in the Baoding area, and patients infected with MRMP strains exhibited more severe clinical features and increased LDH and D-dimer. M3562 was the predominant resistant clone., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Sun, Wang, Qi, Tang, Wang, Han, Shi, Bi, Jiao and Shen.)

Snoring is a common condition in the general population, and the management of snoring requires a better understanding of its mechanism through a fluid-structure interaction (FSI) perspective. Despite the recent popularity of numerical FSI techniques, outstanding challenges are accurately predicting airway deformation and its vibration during snoring due to complex airway morphology. In addition, there still needs to be more understanding of snoring inhibition when lying on the side, and the possible effect of airflow rates, as well as nose or mouth-nose breathing, on snoring remains to be investigated. In this study, an FSI method verified against in vitro models was introduced to predict upper airway deformation and vibration. The technique was applied to predict airway aerodynamics, soft palate flutter, and airway vibration in four sleep postures (supine, left/right lying, and sitting positions) and four breathing patterns (mouth-nose, nose, mouth, and unilateral nose breathing). It was found that, at given elastic properties of soft tissues, the evaluated flutter frequency of 19.8 Hz in inspiration was in good agreement with the reported frequency of snoring sound in literature. Reduction in flutter and vibrations due to the mouth-nose airflow proportion changes were also noticed when having side-lying and sitting positions. Breathing through the mouth results in larger airway deformation than breathing through the nose or mouth-nose. These results collectively demonstrate the potential of FSI for studying the physics of airway vibration and clarify to some degree the reason for snoring inhibition during sleep postures and breathing patterns., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [All methods of this study were carried out by the declaration of research involving human subjects and the regional ethical and scientific guidelines in Dalian, China. The study was approved by the regional ethics review boards in Dalian, China (DLKQLL201604). The data were retrospectively collected at the Department of Orthodontics (Stomatological hospital, Dalian, China) in 2016. Informed consent was obtained from all patients or their legal guardians.]., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: The absence of proper pathogen treatment in the early stages can result in missing out on treatment chances or the overuse of antibiotics, both of which are the primary factors behind fatalities caused by lung infections. In this study, we aimed to investigate the efficacy of metagenomic next-generation sequencing (mNGS) in comparison to conventional detection methods in detecting infectious pathogens., Patients and Methods: In this retrospective study, the infection pathogens of 104 patients were examined, and 86 bronchoalveolar lavage fluid (BALF), eight pleural effusions, and ten sputum samples were collected. The conventional detection approaches and mNGS analysis were used to determine the infection pathogen profiles and their detection rates were analyzed., Results: Our study showed that mNGS was more sensitive (89.42%) than the conventional detection methods (56.73%) (p < 0.001), with a 32.69% improvement in sensitivity. The efficacy of mNGS in detecting mixed infections was significantly higher than that of conventional detection methods, with a detection rate of 85.29% compared to 17.65% (p < 0.001). The study demonstrated that mNGS had a higher sensitivity than the conventional detection methods when it came to diagnosing pulmonary infections, making it a potentially useful tool for clinical diagnosis., Conclusions: Combining mNGS with other pathogenic detection techniques can be an effective way to increase the rate of detecting pulmonary infections, as well as to provide guidance for treatment adjustments. Furthermore, the timing of sample collection and antibiotic administration can influence the effectiveness of mNGS when used on BALF specimens.

Lung cancer is a malignant tumor with high rates of mortality and shows significant hereditary predisposition. Previous genome-wide association studies suggest that rs748404, located at promoter of TGM5 (transglutaminase 5), is associated with lung carcinoma. By analysis of 1000 genomes project data for three representative populations in the world, another five SNPs are identified to be in strong linkage disequilibrium with rs748404, thus suggesting that they may also be associated with lung carcinoma risk. However, it is ambiguous about the actually causal SNP(s) and the mechanism for the association. Dual-luciferase assay indicates that the functional SNPs are not rs748404, rs12911132 or rs35535629 but another three SNPs (rs66651343, rs12909095 and rs17779494) in lung cell. By chromosome conformation capture, it is disclosed that the enhancer encompassing the two SNPs, rs66651343 and rs12909095, can interact with the promoter of CCNDBP1 (cyclin D1 binding protein 1). RNA-seq data analysis indicates that CCNDBP1 expression is dependent on the genotype of these two SNPs. Chromatin immunoprecipitation assay suggests that the fragments spanning rs66651343 and rs12909095 can bind with the transcription factors, cut like homeobox 1 and SRY-box transcription factor 9, respectively. Our results establish the connection between genetic variations at this locus and lung cancer susceptibility., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Drug-resistant advanced lung adenocarcinoma (LUAD) is an aggressive malignancy with limited treatment options. A therapeutic strategy for drug-resistant LUAD is to target the tumor associated macrophages (TAMs), because they play an important role in tumor immune escape, progression and metastasis. In this study, we conducted in vivo and in vitro investigation of the inhibitory effect of arsenic trioxide (ATO) on polarization of TAMs educated by LUAD. We found that ATO at a concentration of 4 μM disrupted the Notch-dependent positive feedback loop between LUAD and TAMs. In this loop, ATO inhibited the expression of Jagged1 and Notch1 in LUAD and suppressed M2 polarization via down-regulating Notch-dependent paracrine of CCL2 and IL1β. As a result, the secretion of M2-derived TGF-β1 decreased, thus inducing inhibitions of LUAD proliferation, migration, invasion, colony formation and epithelial-mesenchymal transition. In xenograft mouse models, ATO significantly inhibited tumor growth and down-regulated infiltration of M2-like TAMs in tumor tissues. In clinical LUAD biopsy samples, high Jagged1/Notch1 expression positively correlated with tumor-infiltrated M2-like TAMs, leading to poor prognosis. In conclusion, our results identified a novel tumor immunomodulating function for ATO, which can inhibit the polarization of M2-type TAMs to exert anti-tumor effects in the tumor microenvironment. Our results demonstrated the translational potential of repurposing ATO to target TAMs for lung adenocarcinoma treatment., 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 © 2023 Elsevier B.V. All rights reserved.)

Our previous work identified one region upstream human UGT2B4 (UDP glucuronosyltransferase family 2 member B4) which is associated with breast cancer and under balancing selection. However, the distribution, functional variation and molecular mechanism underlying breast cancer and balancing selection remain unclear. In current study, the two haplotypes with deep divergence are described by analyzing 1000 genomes project data and observed to be with high frequencies in all human populations. Through population genetics analysis and genome annotation, the potential functional region is identified and verified by reporter gene assay. Further mutagenesis indicates that the functional mutations are rs66862535 and rs68096061. Both SNPs can alter the interaction efficiency of transcription factor POU2F1 (POU class 2 homeobox 1). Through chromosome conformation capture, it is identified that the enhancer containing these two SNPs can interact with UGT2B4 promoter. Expression quantitative trait loci analysis indicates that UGT2B4 expression is dependent on the genotype of this locus. The common haplotype in human is lost in four genomes of archaic hominins, which suggests that Neanderthal and Denisovan should present relatively lower UGT2B4 expression and further higher steroid hormone level. This study provides new insight into the contribution of ancient population structure to human phenotypes., (© 2023. The Author(s).)

The uvula flapping is one of the most distinctive features of snoring and is critical in affecting airway aerodynamics and vibrations. This study aimed to elucidate the mechanism of pharyngeal vibration and pressure fluctuation due to uvula flapping employing fluid-structure interaction simulations. The followings are the methodology part: we constructed an anatomically accurate pediatric pharynx model and put attention on the oropharynx region where the greatest level of upper airway compliance was reported to occur. The uvula was assumed to be a rigid body with specific flapping frequencies to guarantee proper boundary conditions with as little complexity as possible. The airway tissue was considered to have a uniform thickness. It was found that the flapping frequency had a more significant effect on the airway vibration than the flapping amplitude, as the flapping uvula influenced the pharyngeal aerodynamics by altering the jet flow from the mouth. Breathing only through the mouth could amplify the effect of flapping uvula on aerodynamic changes and result in more significant oropharynx vibration., (© 2023. The Author(s).)