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Abstract Introduction This study aims to compare sagittal condylar inclination (SCI) measurements derived from three workflows: intraoral scan (IOS) aligned with cone-beam computed tomography (CBCT), IOS aligned with facial scan (FS), and a jaw motion analyzer (JMA) system, in a cohort of young individuals with established normal occlusion. Additionally, the study aims to identify sources contributing to variance in these measurement approaches. Methods Twenty-four healthy individuals exhibiting normal occlusion were enrolled in this clinical trial. The SCI was delineated using a virtual articulator (VA) by aligning IOS with both CBCT and FS, creating two distinct workflows labeled CBCT-IOS and FS-IOS, respectively. Concurrently, SCI measurements were also acquired using a JMA. The normality of data distribution for the difference in bilateral SCI measurements within each workflow was tested using the Shapiro-Wilk test. Depending on the outcomes of this test, we utilized either a paired-sample T-test or Wilcoxon test for bilateral SCI comparisons. The inter-workflow differences were assessed using the Kruskal-Wallis H test. Bland-Altman plots were assess the interchangeability and consistency across each pair of digital methods and to evaluate the aggregate consistency among the trio of digital approaches. Results The analysis revealed that the CBCT-IOS workflow yielded the lowest average SCI measurements, whereas the JMA workflow produced the highest values. No significant differences were found in the SCI measurements between the left and right sides obtained by CBCT-IOS and JMA (P > .05), with the exception of the FS-IOS workflow (P = .002). Additionally, inter-flow comparisons revealed no significant differences in SCI measurements (P > .05), except when contrasting the SCI as measured by CBCT-IOS and JMA (P = .0131). The Bland-Altman plots demonstrated a high degree of consistency and 95% limits of agreement across the three digital workflows. Conclusion SCI measurements obtained from the three digital workflows exhibit a high degree of consistency and are interchangeable, affirming their clinical applicability for precise SCI assessment in young individuals with normal occlusion.

Abstract Higher-order topological insulators (HOTIs) are unique materials hosting topologically protected states, whose dimensionality is at least by 2 lower than that of the bulk. Topological states in such insulators may be strongly confined in their corners which leads to considerable enhancement of nonlinear processes involving such states. However, all nonlinear HOTIs demonstrated so far were built on periodic bulk lattice materials. Here, we demonstrate the first nonlinear photonic HOTI with the fractal origin. Despite their fractional effective dimensionality, the HOTIs constructed here on two different types of the Sierpiński gasket waveguide arrays, may support topological corner states for unexpectedly wide range of coupling strengths, even in parameter regions where conventional HOTIs become trivial. We demonstrate thresholdless spatial solitons bifurcating from corner states in nonlinear fractal HOTIs and show that their localization can be efficiently controlled by the input beam power. We observe sharp differences in nonlinear light localization on outer and multiple inner corners and edges representative for these fractal materials. Our findings not only represent a new paradigm for nonlinear topological insulators, but also open new avenues for potential applications of fractal materials to control the light flow.

ObjectiveTo understand the prevalence of hepatitis C virus (HCV) infection and the genotypes of prevalent HCV among drug users in the Inner Mongolia Autonomous Region (Inner Mongolia). MethodsA cross-sectional survey was conducted from April to June 2022 among all newly admitted drug users (n = 1 659) at AIDS sentinel surveillance sites in four cities of Inner Mongolia. Participants were interviewed and blood samples were collected for relevant information, anti-HCV/HCV nucleic acid detection, and genotyping of HCV RNA-positive specimens. Enumeration data were described by using proportions, and the chi-squared test was taken for comparisons between groups. Multivariate logistic regression analysis was carried out to identify risk factors for HCV infection among drug users. ResultsAmong 1 659 drug users aged 43.67 ± 9.52 years, 98.01% were male; 89.33% were of Han ethnicity; 85.65% had local household registration; 46.05% were married or cohabiting; and 73.54% reported education of junior high school and below. HCV infection was diagnosed in 13.62% of all drug users. The most common HCV genotypes among HCV-infected individuals were 1b, 3a, and 3b, and the majority of infections with different genotypes had intermediate or high HCV RNA viral loads. Multivariate logistic regression analysis showed that injecting and needle-sharing drug users had a significantly increased risk of HCV infection compared with those without the two drug use behaviors, with odds ratios (95% confidence intervals) of 2.994 (2.243 – 3.995) and 8.217 (4.128 – 16.355), respectively. ConclusionThe prevalent HCV genotypes among HCV-infected drug users in Inner Mongolia are 1b and 3a, and genotype 3a HCV infections have higher viral loads. Strengthening drug control, regular testing and treatment of HCV infection among drug users should be implemented to promptly detect and intervene in HCV infection in the population.

Abstract Background Dietary fiber (DF) consumption was reported to improve insulin sensitivity, change the tryptophan metabolism, and alter the gut microbiota. Herein, this study aimed to investigate the effects of DF consumption on insulin sensitivity, tryptophan metabolism, and gut microbiota composition in sows during late pregnancy, and explore the relationship between tryptophan metabolites and insulin sensitivity regulated by DF supplementation. Results Twelve sows were randomly assigned to two dietary treatment groups (six/group): the low-fiber (LF) group, which was fed a basal diet, and the high-fiber (HF) group, which was fed the basal diet supplemented with 22.60 g/kg inulin and 181.60 g/kg cellulose. During late pregnancy, meal test, glucose tolerance test, and insulin challenge test were used to investigate the insulin sensitivity of sows, using the percutaneous brachiocephalic vein catheterization technique. High DF consumption resulted in improved insulin sensitivity, especially during the second and third trimesters, and promoted serotonin production from tryptophan. Additionally, plasma serotonin concentration was positively correlated with the insulin sensitivity index during late pregnancy. Moreover, DF consumption elevated fecal short-chain fatty acid (SCFA) concentrations, altered fecal microbial diversity, and increased the abundances of Rikenellaceae_RC9_gut_group, Alloprevotella, Parabacteroides, Roseburia, and Sphaerochaeta, which were positively correlated to plasma serotonin concentration. Conclusions DF consumption improved insulin sensitivity during late pregnancy in sows, which improved microbial diversity in fecal samples and increased fecal SCFA concentrations, resulting in a positive correlation with plasma serotonin level.

BackgroundThe continuous emergence and spread of polymyxin-resistant Acinetobacter baumannii pose a significant global health challenge, necessitating the development of novel therapeutic strategies. Aloe, with its long-standing history of medicinal use, has recently been the subject of substantial research for its efficacy against pathogenic infections.MethodsThis study investigates the potential application of anthraquinone components in aloe against polymyxin-resistant A. baumannii by liquid chromatography-mass spectrometry, in vitro activity assessment, and construction of animal infection models.ResultsThe findings demonstrate that aloe emodin, emodin, rhein, and their mixtures in equal mass ratios (EAR) exhibit strain-specific antibacterial activities against polymyxin-resistant A. baumannii. Co-administration of EAR with EDTA synergistically and universally enhanced the antibacterial activity and bactericidal efficacy of polymyxins against polymyxin-resistant A. baumannii, while also reducing the frequency of polymyxin-resistant mutations in polymyxinssensitive A. baumannii. Following toxicity assessment on human hepatic and renal cell lines, the combination therapy was applied to skin wounds in mice infected with polymyxin-resistant A. baumannii. Compared to monotherapy, the combination therapy significantly accelerated wound healing and reduced bacterial burden.ConclusionsThe combination of EAR and EDTA with polymyxins offers a novel therapeutic approach for managing skin infections caused by polymyxinresistant A. baumannii.

Melatonin is a conserved pleiotropic molecule in animals and plants. Melatonin is involved in many development processes and stress responses; thus, exploring its function in plants, particularly in horticultural plants, has become a rapidly developing field. Many studies have revealed that phytomelatonin acts as a plant biostimulant and increase its tolerance to various abiotic stressors, including extreme temperature, drought, osmotic disturbance, heavy metals, and ultraviolet (UV). Melatonin appears to have roles in the scavenging of reactive oxygen species (ROS) and other free radicals, affecting the primary and secondary metabolism of plants, regulating the transcripts of stress-related enzymes and transcription factors, and crosstalk with other hormones under different environmental conditions. This pleiotropy makes phytomelatonin an attractive regulator to improve resistance to abiotic stress in plants. The recent discovery of the potential phytomelatonin receptor CAND2/PMTR1 and the proposition of putative models related to the phytomelatonin signaling pathways makes phytomelatonin a new plant hormone. Based on relevant studies from our laboratory, this review summarizes the phytomelatonin biosynthetic and metabolic pathways in plants and the latest research progress on phytomelatonin in abiotic stress of horticultural plants. This study will provide a reference for elucidating the regulatory mechanism of phytomelatonin affecting the resistance to abiotic stress in plants.

Abstract Recent development of new immune checkpoint inhibitors has been particularly successfully in cancer treatment, but still the majority patients fail to benefit. Converting resistant tumors to immunotherapy sensitive will provide a significant improvement in patient outcome. Here we identify Mi-2β as a key melanoma-intrinsic effector regulating the adaptive anti-tumor immune response. Studies in genetically engineered mouse melanoma models indicate that loss of Mi-2β rescues the immune response to immunotherapy in vivo. Mechanistically, ATAC-seq analysis shows that Mi-2β controls the accessibility of IFN-γ-stimulated genes (ISGs). Mi-2β binds to EZH2 and promotes K510 methylation of EZH2, subsequently activating the trimethylation of H3K27 to inhibit the transcription of ISGs. Finally, we develop an Mi-2β-targeted inhibitor, Z36-MP5, which reduces Mi-2β ATPase activity and reactivates ISG transcription. Consequently, Z36-MP5 induces a response to immune checkpoint inhibitors in otherwise resistant melanoma models. Our work provides a potential therapeutic strategy to convert immunotherapy resistant melanomas to sensitive ones.

Abstract Background This study aimed to evaluate the characteristics of mandibular protrusive condylar trajectory in adolescents with skeletal Class II Division 1 malocclusion and the changes of condylar trajectory during mandibular advancement (MA) treatment using clear functional aligners. Methods This prospective study consisted of a cross-sectional study and a longitudinal study. In cross-sectional study, sixty-one adolescents were divided into two groups: Class I (n = 30) and Class II Division 1 (n = 31). The condylar trajectory was measured and compared using the Mann–Whitney U test. The longitudinal study was the MA treatment group using clear functional aligner and consisted of 16 participants from Class II Division 1group. The condylar trajectory was collected at three-time points: pre-treatment (T1), during MA treatment at approximately 3 months (T2, 105.6 days average), and at the end of MA treatment (T3, 237.6 days average). The changes at T1, T2, and T3, as well as the symmetry between the left and right condyles across all groups, were examined using the Wilcoxon paired test. Results A greater increase in the anteroposterior displacement and space displacement during protrusive movements was observed in the Class II Division 1 group compared with that in the Class I group, with a large difference being observed in the left and right condylar movements. The condylar anteroposterior displacement and space displacement decreased significantly at T2 and increased significantly at T3; however, no significant difference was observed between T1 and T3. A significant difference was observed between the condylar movement on the left and right sides at T1; however, no significant difference was observed at T2 and T3. Conclusions Adolescents with Class II Division 1 malocclusion had higher protrusive capacity than those with Class I. Moreover, their left and right condylar motion was more asymmetric. The range of condyle motion decreased first and then increased during MA therapy, and the left and right condyle movement became more symmetrical, which may be the adaptive response of neuromuscular function to the changes in jaw position.

π modes are unique topological edge states appearing in Floquet systems with periodic modulations of the underlying lattice structure in the evolution variable, such as dynamically modulated Su–Schrieffer–Heeger (SSH) lattices. These edge states are anomalous states usually appearing between Floquet replicas of the same band, even if the standard topological index remains zero for this band. While linear and nonlinear π modes were observed in conservative systems, they have never been studied in the nonlinear regime in the non-Hermitian systems with structured gain and losses. Here, we show that the SSH waveguide array with periodically oscillating waveguide positions in the propagation direction and with the parity-time symmetric refractive index landscape can support π modes that are damped or amplified at different ends of the array. By including nonlinearity and nonlinear absorption into our continuous system, we achieve stable lasing in the π mode at one end of the array. The representative feature of this system is that lasing in it is thresholdless and occurs even at low gain–loss amplitudes. The degree of localization of lasing π modes can be flexibly controlled by the amplitude of transverse waveguide oscillations. This work therefore introduces a new type of topological Floquet laser and a route to manipulate π modes by structured gain and losses.

Understanding the challenges faced by second language (L2) learners in lexical tone perception is crucial for effective language acquisition. This study investigates the impact of exaggerated acoustic properties on facilitating Mandarin tone learning for English speakers. Using synthesized tone stimuli, we systematically manipulated pitch contours through three key modifications: expanding the fundamental frequency (F0), increasing F0 (female voice), and extending the overall duration. Our objectives were to assess the influence of F0 expansion, higher F0, longer duration, and varied syllables on Mandarin tone learning and generalization. Participants engaged in a non-adaptive trial-by-trial tone identification task. Mixed-effects logistic regression modeling was used to analyze accuracy across learning phases, acoustic factors, and tones. Findings reveal improvements in accuracy from training to testing and generalization phases, indicating the effectiveness of perceptual training to tone perception for adult English speakers. Tone 1 emerged as the easiest to perceive, while Tone 3 posed the most challenge, consistent with established hierarchies of tonal acquisition difficulty. Analysis of acoustic factors highlighted tone-specific effects. Expanded F0 was beneficial for the identification of Tone 2 and Tone 3 but posed challenges for Tone 1 and Tone 4. Additionally, longer durations also exhibited varied effects across tones, aiding in the identification of Tone 3 and Tone 4 but hindering Tone 1 identification. The higher F0 was advantageous for Tone 2 but disadvantageous for Tone 3. Furthermore, the syllable ma facilitated the identification of Tone 1 and Tone 2 but not for Tone 3 and Tone 4. These findings enhance our understanding of the role of acoustic properties in L2 tone perception and have implications for the design of effective training programs for second language acquisition.

Objective: Understanding the characteristics of alveolar bone resorption in an East Asian population after maxillary incisor extraction and providing a reference for implant treatment plans. Study design: Cone-beam computerized tomography (CBCT) data of 125 East Asian patients with unilateral extraction of maxillary incisors for 3 months were collected. The alveolar bone width and height in the extraction sites were measured and compared with the corresponding contralateral sites. Results: The differences in alveolar bone width between the extraction site and contralateral site were as follows: 4.11 mm, 2.68 mm, and 2.09 mm (3 mm, 5 mm, 7 mm apical from CEJ of the contralateral tooth). Data are expressed as the median. The horizontal resorption ratio of alveolar bone was 49.94 %, 31.5 %, and 24.46 %. The difference in alveolar bone height was 0.78 mm. The vertical resorption ratio was 7.78 %. The resorption did not differ significantly between sexes and was not significantly affected by tooth positions. Conclusions: In the studied East Asian population, significant horizontal and vertical alveolar bone resorption occurs after natural healing of maxillary incisor extraction for 3 months. The closer to the alveolar ridge crest, the more significant the horizontal resorption, resulting in an “inverted triangle” shape residual alveolar bone.

Abstract Background Despite radiotherapy ability to significantly improve treatment outcomes and survival in triple-negative breast cancer (TNBC) patients, acquired resistance to radiotherapy poses a serious clinical challenge. Protein disulfide isomerase exists in endoplasmic reticulum and plays an important role in promoting protein folding and post-translational modification. However, little is known about the role of protein disulfide isomerase family member 4 (PDIA4) in TNBC, especially in the context of radiotherapy resistance. Methods We detected the presence of PDIA4 in TNBC tissues and paracancerous tissues, then examined the proliferation and apoptosis of TNBC cells with/without radiotherapy. As part of the validation process, xenograft tumor mouse model was used. Mass spectrometry and western blot analysis were used to identify PDIA4-mediated molecular signaling pathway. Results Based on paired clinical specimens of TNBC patients, we found that PDIA4 expression was significantly higher in tumor tissues compared to adjacent normal tissues. In vitro, PDIA4 knockdown not only increased apoptosis of tumor cells with/without radiotherapy, but also decreased the ability of proliferation. In contrast, overexpression of PDIA4 induced the opposite effects on apoptosis and proliferation. According to Co-IP/MS results, PDIA4 prevented Tax1 binding protein 1 (TAX1BP1) degradation by binding to TAX1BP1, which inhibited c-Jun N-terminal kinase (JNK) activation. Moreover, PDIA4 knockdown suppressed tumor growth xenograft model in vivo, which was accompanied by an increase in apoptosis and promoted tumor growth inhibition after radiotherapy. Conclusions The results of this study indicate that PDIA4 is an oncoprotein that promotes TNBC progression, and targeted therapy may represent a new and effective anti-tumor strategy, especially for patients with radiotherapy resistance.

In order to develop non-spheroidizing annealing 12Cr1MoV hot rolled wire rod ， based on deformation induced phase transition mechanism， the finishing rolling temperature of 830 ℃ and laying temperature of 800 ℃ were adopted. By inhibiting deformation austenite grain recovery and recrystallization process，increasing deformation energy storage， thereby promoting austenite decomposed into ferrite and pearlite. Meanwhile in stage controlled cooling was realized with adjusting the air-cooled roller speed， the quenching microstructures were completely eliminated because prolonging the holding time between 630 ℃ and 750 ℃. The test results are that the tensile strength of 12Cr1MoV hot-rolled wire rod was reduced from 576 MPa to 520 MPa， while reduction of area increasing from 66% to 74%.The elimination of quenched microstructure significantly optimizes the deformation ability of wire rod ，and also avoided holes in the cross-section center or draw break which caused by a small or minimal martensite microstructure are unable to cooperate with deformation . Plastic cracking has not occurred after batch use of multiple specifications by users.

Popular religion in China has been very active ever since the late 1970s, with the restoration of temples and statues, a rising numbers of believers, and people’s increasing enthusiasm for religious activities. Folklore, rituals and legends are also ‘borrowed’ to reinvent tradition to fit in the strand of intangible cultural heritage. Therefore, seemingly reviving religions are also going through the process of de-religionization. Based on my ethnographic work in a Chinese county, I attempted to understand religion’s role in constructing local knowledge and how religious practices are affected by urbanization as well as globalization. The revival of institutional religions like Buddhism and Protestantism comes at the cost of popular religion or popular religious practices. Local deities lost the battle of competing with regional deities, which led to the simplification of local religious knowledge, a decrease in the diversity of deities and the tendency of convergence in terms of deities’ functions and believers’ appeals. A once complicated celestial hierarchy mirroring the imperial dynasty has been replaced by a more universal understanding of either bodhi in Buddhism or salvation in Protestantism. Local knowledge is reinterpreted by these religious teachings in the name of a higher cause of morality.

ObjectiveTo examine iodine nutrition status among pregnant women in Ji'nan city, Shandong province for providing evidence to effective improvement of iodine nutrition in pregnant women. MethodsA monitoring survey was conducted among 4 992 pregnant women recruited in 12 districts/counties of Ji′nan municipality, Shandong province during 2018 – 2021; each of the districts/counties was divided into 5 geographical regions and 20 pregnant women were selected from one subdistrict/town in each of the 5 regions. Table salt samples were collected from households of the pregnant women and urine samples of the pregnant women were also collected. Iodine content of table salt samples was measured with direct titration listed in the General Test Method for Salt Industry: Determination of Iodine (GB/T13025.7) and that of well salt and other fortified table salt samples was determined with arbitration method. Urinary iodine was detected using arsenic cerium catalytic spectrophotometry stated in WS/T107 issued by National Health and Family Planning Commission. Year- and trimester-specific urinary iodine were analyzed. ResultsThe median ( 25% percentile [P25], 75% percentile [P75]) of iodine content was 22.31 (18.18, 25.59) mg/kg for all the 4 992 table salt samples. The coverage rate of iodized table salt was 88.92% (4 439 samples) and the usage rate of qualified iodized table salt was 72.96% (3 642 samples). There were significant yearly and regional differences in iodized salt coverage (χ2 = 72.54, χ2 = 271.04; both P < 0.05) and qualified iodized table salt usage rate (χ2 = 43.03, χ2 = 492.25, both P < 0.05); but the iodized salt coverage and qualified iodized table salt usage rate were not significantly different among the pregnant women in various trimesters of pregnancy (χ2 = 1.07, χ2 = 0.97; both P > 0.05). The median ( P25, P75) of urinary iodine was 145.70 (87.70, 216.00) μg/L for the 4 992 pregnant women. The urinary iodine concentration differed significantly among the pregnant women surveyed in different years (H = 21.97), from various districts/towns (H = 348.78), during various trimesters of pregnancy (H = 41.18), and consuming table salt with different iodine content (H = 13.23) (P < 0.05 for all). ConclusionMild iodine deficiency existed among pregnant women in Ji'nan city during 2018 − 2021, suggesting that relevant measures should be taken to prevent iodine deficiency in the pregnant women.

Abstract Background Lines of evidence indicated that, immune checkpoints (ICs) inhibitors enhanced T cell immune response to exert anti-tumor effects. However, T cell exhaustion has been so far a major obstacle to antitumor immunotherapy in colorectal cancer patients. Our previous studies showed that ginseng-derived nanoparticles (GDNPs) inhibited the growth of various tumors by reprograming tumor-associated macrophages (TAMs) and downregulated the ICs expression on T cells in tumor microenvironment (TME), but the underlying effector mechanisms remained unclear. Methods The correlation between arginase-1 (ARG1) and T cells was computed based on the colorectal cancer patients in TCGA database. In vitro, we observed that GDNPs reprogrammed TAMs inhibited ARG1 release and ultimately ameliorated T cell exhaustion according to several techniques including WB, PCR, ELISA and flow cytometry. We also used an in vivo MC38 tumor-bearing model and administered GDNPs to assess their anti-tumor effects through multiple indices. The mechanism that GDNPs improved T cell exhaustion was further clarified using the bioinformatics tools and flow cytometry. Results GDNPs reprogramed TAMs via reducing ARG1 production. Moreover, normalized arginine metabolism ameliorated T cell exhaustion through mTOR-T-bet axis, resulting in reduced ICs expression and enhanced CD8+ T cells expansion. Conclusions By regulating the mTOR-T-bet axis, GDNPs reprogramed macrophages to regulate ARG1 release, which further ameliorated T cell exhaustion in TME. These findings provided new insights into comprehending the mechanisms underlying the mitigation of T cell exhaustion, which may facilitate the development of innovative therapeutic strategies in the field of cancer treatment.

The excavation of pits will induce the vertical displacement of tunnels and lead to engineering problems. The shape as well as size of a pit, and the complex spatial position relationship between the pit and tunnel will induce different deformation responses of tunnel structures; however, the degree to which each factor influences tunnel structure deformation is still unclear. This paper studied the impact of excavation on the deformation of tunnels via a combination of numerical simulation and orthogonal tests. The deformation of tunnels induced by excavation was studied using a numerical method, after which the sensitivity of influencing factors to tunnel deformation was studied by means of range and variance analyses through a four-factor and three-level orthogonal test. The results show that, for a foundation pit with a long side perpendicular to the tunnel longitude, the excavation has the least influence on tunnel deformation. Tunnel deformation increased with an increase in the excavation depth and decreased with an increase in tunnel–pit vertical and horizontal distance. As the plane shape of the foundation pit is 20 m × 45 m, the depth of excavation is 4 m, the pit tunnel vertical distance is 13 m, and the pit tunnel horizontal distance is 28 m, the tunnel has the least deformation. Based on the results of this study, the position relationship between the pit and the tunnel can be optimized in terms of design and construction, and the aim of controlling tunnel deformation can be achieved.

Nasal administration is a non-invasive method of drug delivery that offers several advantages, including rapid onset of action, ease of use, no first-pass effect, and fewer side effects. On this basis, nose-to-brain delivery technology offers a new method for drug delivery to the brain and central nervous system, which has attracted widespread attention. In this paper, the development status and trends of nasal drug delivery and nose-to-brain delivery technology are deeply analyzed through multiple dimensions: literature research, questionnaire surveys, and patent analysis. First, FDA-approved nasal formulations for nose-to-brain delivery were combed. Second, we collected a large amount of relevant information about nasal drug delivery through a questionnaire survey of 165 pharmaceutical industry practitioners in 28 provinces and 161 different organizations in China. Third, and most importantly, we conducted a patent analysis of approximately 700+ patents related to nose-to-brain delivery, both domestically and internationally. This analysis was conducted in terms of patent application trends, technology life cycle, technology composition, and technology evolution. The LDA topic model was employed to identify technological topics in each time window (1990–2023), and the five key major evolution paths were extracted. The research results in this paper will provide useful references for relevant researchers and enterprises in the pharmaceutical industry, promoting the further development and application of nasal drug delivery and nose-to-brain delivery technology.

Amidst population aging and lifestyle shifts, the incidence of neurological disorders such as stroke and Alzheimer’s disease is increasing, profoundly affecting patients’ cognitive functions and everyday life. Conventional cognitive rehabilitation approaches often necessitate substantial time and manpower, yet their outcomes remain uncertain. Although computer-assisted cognitive rehabilitation offers convenience, it can be somewhat monotonous in its experience. Virtual reality (VR) technology has introduced a novel pathway for cognitive rehabilitation, enhancing personalization and outcome assessment through tailored immersive environments and real-time data recording. This paper aims to survey the application of VR in cognitive rehabilitation, examining its impact on improving memory, attention, motor function, and social skills. A systematic review methodology was employed, following PRISMA guidelines, to identify and analyze relevant studies from 2010 to 2023. Recognizing that patients with different conditions have varying needs for the immersive and social aspects of VR, we propose the Multi-Dimensional VR Cognitive Rehabilitation Theory Model (MD-VRCRTM). This model categorizes cognitive rehabilitation technologies into six primary types: individual immersive, individual semi-immersive, individual non-immersive, multiplayer immersive, multiplayer semi-immersive, and multiplayer non-immersive rehabilitation systems. This categorization aims to cater to the specific requirements of various patients. For instance, individuals with autism spectrum disorder (ASD) may benefit more from multiplayer VR applications to enhance social skills; those with Parkinson’s disease (PD) might profit from immersive VR to facilitate motor function recovery; stroke and traumatic brain injury (TBI) patients may require highly immersive VR experiences to boost concentration and treatment efficacy; and Alzheimer’s disease (AD) patients may be better suited to non-immersive or semi-immersive VR to minimize cognitive load and receive cognitive stimulation.

Abstract Background Forkhead box (FOX) proteins belong to one of the largest transcription factor families and play crucial roles in the initiation and progression of cancer. Prior research has linked several FOX genes, such as FOXA1 and FOXM1, to the crucial process of carcinogenesis. However, the overall picture of FOX gene family across human cancers is far from clear. Methods To investigate the broad molecular signatures of the FOX gene family, we conducted study on multi‐omics data (including genomics, epigenomics and transcriptomics) from over 11,000 patients with 33 different types of human cancers. Results Pan‐cancer analysis reveals that FOX gene mutations were found in 17.4% of tumor patients with a substantial cancer type‐dependent pattern. Additionally, high expression heterogeneity of FOX genes across cancer types was discovered, which can be partially attributed to the genomic or epigenomic alteration. Co‐expression network analysis reveals that FOX genes may exert functions by regulating the expression of both their own and target genes. For a clinical standpoint, we provided 103 FOX gene‐drug target‐drug predictions and found FOX gene expression have potential survival predictive value. All of the results have been included in the FOX2Cancer database, which is freely accessible at http://hainmu‐biobigdata.com/FOX2Cancer. Conclusion Our findings may provide a better understanding of roles FOX genes played in the development of tumors, and help to offer new avenues for uncovering tumorigenesis and unprecedented therapeutic targets.

Abstract This study aimed to evaluate the potential of exosomes from cancer cells to predict chemoresistance in pancreatic cancer (PC) and explore the molecular mechanisms through RNA-sequencing and mass spectrometry. We sought to understand the connection between the exosomal Medium-chain acyl-CoA dehydrogenase (ACADM) level and the reaction to gemcitabine in vivo and in patients with PC. We employed loss-of-function, gain-of-function, metabolome mass spectrometry, and xenograft models to investigate the effect of exosomal ACADM in chemoresistance in PC. Our results showed that the molecules involved in lipid metabolism in exosomes vary between PC cells with different gemcitabine sensitivity. Exosomal ACADM (Exo-ACADM) was strongly correlated with gemcitabine sensitivity in vivo, which can be used as a predictor for postoperative gemcitabine chemosensitivity in pancreatic patients. Moreover, ACADM was found to regulate the gemcitabine response by affecting ferroptosis through Glutathione peroxidase 4 (GPX4) and mevalonate pathways. It was also observed that ACADM increased the consumption of unsaturated fatty acids and decreased intracellular lipid peroxides and reactive oxygen species (ROS) levels. In conclusion, this research suggests that Exo-ACADM may be a viable biomarker for predicting the responsiveness of patients to chemotherapy.

Frozen dough technology is widely used in the industrial production of flour products, however, frozen dough technology in the application process will still be flawed, resulting in frozen dough and final product quality deterioration. In this study, differential scanning calorimetry (DSC) was used to analyze the changes of thermal characteristics during dough freezing. The effects of different freezing temperatures and freezing center temperatures on the quality of frozen dough and final noodles were studied to determine the optimal freezing temperature and freezing center temperature. The results showed that compared with −20 ℃, the freezing rates of −30 and −40 ℃ were −0.44 and −0.51 ℃·min−1, respectively, with faster freezing rates, shorter freezing time for the central temperature to drop to −18 ℃, shortest time to pass through the maximum ice crystal generation zone, and smaller and more uniform ice crystal volume formed. The frozen water content of dough and the cooking loss rate of noodles decreased to the lowest at −30 ℃. Under the freezing conditions of −30 and −40 ℃, there was no significant difference in water absorption and sensory score (P>0.05). The shear force, hardness, elasticity and chewiness of noodles reached the maximum at −30 ℃ with the decrease of freezing temperature, while there was no significant difference in adhesion (P>0.05). At the freezing center temperature of −18 ℃, the frozen water content of frozen dough was the least, the cooking loss rate, water absorption rate of frozen dough noodles were the lowest, the texture characteristics were the best, and the sensory score was the highest. This study would provide a reference for improving the quality of frozen noodle dough in industry.

Abstract Background To evaluate the quantity and quality of bone in the newly formed edentulous area produced by the orthodontic implant site-switching technique. Methods The bilateral maxillary first premolars of five beagle dogs were extracted and bone defects were created. The right and left sides of the maxilla were randomly divided into control and experimental sides. On the experimental side, the maxillary second premolar was mesially moved into the position of the missing first premolar. On the control side, the second maxillary premolar was extracted. Six months later, the beagles were euthanized. Microcomputer tomography was used to analyze bone microstructure parameters, alveolar bone height and alveolar bone width of the regenerated bone. Histological analysis was performed by staining tissue sections with toluidine blue. Results Median BV/TV values in the experimental group (81.78%) were significantly larger than those in the control group (35.67%; p = 0.04). Median Tb.Sp values in the experimental group (0.14 mm) were significantly lower than those in the control group (0.54 mm; p = 0.04). Median Tb.Th values in the experimental group (0.48 mm) were significantly higher than those in the control group (0.21 mm; p = 0.04). Median Tb.Pf values in the experimental group (0.65/mm) were significantly lower than those in the control group (3.15/mm; p = 0.04). There was no significant difference in the trabecular number (Tb.N) between the two groups (p = 0.23). The median alveolar bone height values in the experimental group (-0.81 mm) were significantly higher than those in the control group (-2.11 mm; p = 0.04) at a distance 5 mm from the mesial CEJ of the third premolar. The median alveolar bone height values in the experimental group (0.45 mm) were significantly higher than those in the control group (-1.70 mm; p = 0.04) at a distance 6 mm from the mesial CEJ of the third premolar. There was no significant difference in alveolar bone width when compared between the two groups (p > 0.05). Conclusions The newly formed edentulous area created by orthodontic treatment had more compact and thicker trabeculae than the extraction socket. Furthermore, the newly formed edentulous area had a greater alveolar bone height available for the placement of implants.

Abstract Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and heterogeneous neurodevelopmental disorder in children and has a high chance of persisting in adulthood. The development of individualized, efficient, and reliable treatment strategies is limited by the lack of understanding of the underlying neural mechanisms. Diverging and inconsistent findings from existing studies suggest that ADHD may be simultaneously associated with multivariate factors across cognitive, genetic, and biological domains. Machine learning algorithms are more capable of detecting complex interactions between multiple variables than conventional statistical methods. Here we present a narrative review of the existing machine learning studies that have contributed to understanding mechanisms underlying ADHD with a focus on behavioral and neurocognitive problems, neurobiological measures including genetic data, structural magnetic resonance imaging (MRI), task-based and resting-state functional MRI (fMRI), electroencephalogram, and functional near-infrared spectroscopy, and prevention and treatment strategies. Implications of machine learning models in ADHD research are discussed. Although increasing evidence suggests that machine learning has potential in studying ADHD, extra precautions are still required when designing machine learning strategies considering the limitations of interpretability and generalization.

Objectives: This study examined and compared the effects of functional and running high-intensity interval training (HIIT) on body composition, cardiorespiratory fitness, and muscular fitness of young adults with overweight or obesity.Methods: Forty-five participants (22.1 ± 2.1 years, BMI = 25.2 ± 1.0 kg/m2) were assigned to functional HIIT (HIIT-F; n = 15), running HIIT (HIIT-R; n = 15), or non-training control group (CON; n = 15). Participants in HIIT-F and HIIT-R performed functional exercise based-HIIT (four sets of all-out whole-body exercises including jumping jacks, squats, twist jumps and mountain climbers, et al.) and running HIIT (four sets of running on a treadmill) for 12 weeks, respectively. Body composition, muscular fitness, and cardiorespiratory fitness were assessed pre and post intervention.Results: Both HIIT-F and HIIT-R significantly improved the body composition and cardiorespiratory fitness, with HIIT-F induced greater improvements in lean mass (+1.623 vs. −1.034 kg, p < 0.001), back strength (+6.007 vs. +3.333 kg, p < 0.01), and push-ups (+5.692 vs. 1.923 reps, p < 0.001) than that in HIIT-R. HIIT-R reduced more visceral fat area (VFA) (−11.416 vs. −4.338 cm2, p = 0.052) and induced similar improvement in cardiorespiratory fitness (VO2max, +2.192 vs. +2.885 mL/kg/min, p = 0.792) with HIIT-F.Conclusion: Twelve weeks of HIIT-R or HIIT-F improved physical fitness among young adults with overweight or obesity. Despite the similar impact on cardiorespiratory fitness, HIIT-F generates a better positive effect on muscular fitness relative to HIIT-R, which could be partly explained by the greater increase in lean mass after HIIT-F intervention.

Background. Growing evidence has revealed that m6A modification of long noncoding RNAs (lncRNAs) dynamically controls tumor stemness and tumorigenesis-related processes. However, the prognostic significance of m6A-related lncRNAs and their associations with stemness in low-grade glioma (LGG) remain to be clarified. Methods. A multicenter transcriptome analysis of lncRNA expression in 1,247 LGG samples was performed in this study. The stemness landscape of LGG tumors was presented and associations with clinical features were revealed. The m6A-related lncRNAs were identified between stemness groups and were further prioritized via least absolute shrinkage and selection operator Cox regression analysis. A risk score model based on m6A-related lncRNAs was constructed and validated in external LGG datasets. Results. Based on the expression of LINC02984, PFKP-DT, and CRNDE, a risk model and nomogram were constructed; they successfully predicted the survival of patients and were extended to external datasets. Significant correlations were observed between the risk score and tumor stemness. Moreover, patients in different risk groups exhibited distinct tumor immune microenvironments and immune signatures. We finally provided several potential compounds suitable for specific risk groups, which may aid in LGG treatment. Conclusions. This novel signature presents noteworthy value in the prediction of prognosis and stemness status for LGG patients and will foster future research on the development of clinical regimens.

The aim of this study was to establish a new method for the determination of homoisoflavanones (Ⅲ, Ⅳ, V) in polygonatum odoratum(POD) by combination of thin layer chromatography (TLC) and chemical derivative resonance Raman spectroscopy (RRS). The twice chromatography method of TLC was used to improve the specificity of the component to be tested; the method of the relative Rf was used to reduce the use of the reference substance of the component to be tested; the chemical derivatization method was used to improve the signal intensity of Raman spectrum for the component to be tested in POD, so as to obtain a trace amount fingerprint structure information of the measured component. The method exhibits robust specificity, high sensitivity, and reliable stability, there by offering a novel reference approach for the identification and evaluation of homoisoflavanones (Ⅲ, Ⅳ, V) in POD.

Abstract To investigate the effect of pentoxifylline (PTX) on Chlorine (Cl2)-induced acute lung injury (ALI) by single-cell RNA sequencing (scRNA-seq). Female BALB/c mice were exposed to Cl2 at 400 ppm for 15 min. H&E staining was used to observe the degree of lung injury. scRNA-seq was conducted to analysis of normal and Cl2-exposed mice lung tissues. Immunofluorescence was used to observe genes of interest. Thirty-two mice were randomly divided into four groups: Control, Cl2, Cl2+Fer-1, Cl2+PTX. TEM, WB and ELISA were used to detect ferroptosis-related indicators. The 5, 8, 10, 12, 16, 20 clusters were epithelial cells and 4, 15, 18, 19, 21 clusters were endothelial cells. Pseudo-time analysis revealed the differentiation trajectory of epithelial cells and key regulatory genes (Gclc, Bpifa1, Dnah5 and Dnah9) during the process of injury. Cell–cell communication analysis identified several important receptor–ligand complexes (Nrp1-Vegfa, Nrp2-Vegfa, Flt1-Vegfa and Flt4-Vegfa). Ferroptosis were found up-regulated in epithelial and endothelial cells by GSVA analysis. Highly expressed genes to which closely related ferroptosis were found by SCENIC analysis. PTX could significantly decrease the levels of MDA and abnormal high expression of solute carrier family 7 member 11 (SLC7A11, the key transporter of cystine) as well as increase the expression of GSH/GSSG and glutathione peroxidase 4 (GPX4) (p