Lumbar Apex Position as an Independent Risk Factor for Adjacent Segment Diseases in Patients Undergoing Short-level Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate whether lumbar apex position had an impact on the development of adjacent segment disease (ASD) following transforaminal lumbar interbody fusion (TLIF). SUMMARY OF BACKGROUND DATA: Previous studies have demonstrated that solely concentrating on lumbar lordosis value is not suitable and neglecting the significance of lumbar apex can lead to mechanical complications. However, the relationship between lumbar apex and ASD is still not well understood. METHODS: In this retrospective study, 234 consecutive patients who underwent L3-5 or L4-5 TLIF for degenerative diseases were reviewed. The study evaluated the associations between sagittal parameters and pelvic incidence (PI). Patients were labeled "matched" when lumbar apex position aligned with the theoretical target, and "mismatched" when it did not. Multivariate analysis was applied to find the independent risk factors of ASD. Additionally, a focused sub-analysis was performed based on the lumbar apex position (ideal match, cranial from ideal, and caudal from ideal). RESULTS: After an average follow-up period of 70.6 months, 68 cases were identified as having ASD. Postoperatively, 64.7% (44 out of 68) of the patients with ASD exhibited a mismatched lumbar apex, compared to 41% (68 out of 166) of those without ASD (p < 0.001). PI correlated significantly with proximal lordosis (PL) and lordosis distribution index (LDI), but not with distal lordosis (DL). Multivariate analysis identified age, L3-5 fusion, postoperative DL, and postoperative mismatched lumbar apex as independent risk factors of ASD. Upon the sub-analysis, it was discovered that there were unique compensatory strategies in the cranial and caudal groups, with notable variations in postoperative DL, PL, and LDI among three groups (all p value<0.05). CONCLUSION: Lumbar apex position significantly influenced the risk of ASD. To restore the lumbar apex to its ideal position, a proper value and distribution of DL should be attained.

Systematic evaluation of integration between China's digital economy and sports industry: Two-stage grey relational analysis and vector autoregressive model.

OBJECTIVES: The development of the digital economy constitutes a key component of China's endeavors to advance towards "Digital China." The sports industry functions as a new catalyst for high-quality economic growth. This study systematically evaluated the integration between these two sectors. METHODS: First, we conducted two levels of grey relational analysis to assess their integration between 2016 and 2021. Second, we conducted a VAR analysis to determine whether their integration between 2009 and 2021 represents a causal relationship. RESULTS: At the macro level, the grey relational analysis reveals that the sports industry (grade = 0.770) ranked second among China's eight key economic sectors in terms of digital economy integration. At the meso level, a wide variation (ranging from 0.606 to 0.789) existed in the grade of integration between the digital economy and the sub-sectors of the sports industry. According to the VAR model, the digital economy does not Granger cause (p = 0.344) the growth of the sports industry. CONCLUSIONS: This study yielded two added values to the existing literature: First, there exists a sectoral imbalance in the digitization process; second, the explosive growth of the sports industry was not primarily caused by the digital economy. Accordingly, the "sports + digital" complex is still in the first wave of technological integration. We propose three policy recommendations, namely, sectoral synergistic development, overtaking via esports IP, and new economy and new regulation. Collectively, these findings provide updated insights for the digital transformation towards "building a leading sports nation" and "Digital China."

Prediction model for low bone mass mineral density in type 2 diabetes: an observational cross-sectional study.

PURPOSE: Considering the prevalence of type 2 diabetes (T2D), osteoporosis should be considered a serious complication. However, an effective tool for the assessment of low bone mass mineral density (BMD) in T2D patients is not currently available. Therefore, the aim of our study was to establish a simple-to-use risk assessment tool by exploring risk factors for low BMD in T2D patients. METHODS: This study included 436 patients with a low BMD and 381 patients with a normal BMD. Multiple logistic regression analysis was performed to evaluate risk factors for low BMD in T2D patients. A nomogram was then developed from these results. A receiver operating characteristic (ROC) curve, calibration plot, and goodness-of-fit test were used to validate the nomogram. The clinical utility of the nomogram was also assessed. RESULTS: Multivariate logistic regression indicated that age, sex, education, body mass index (BMI), fasting C-peptide, high-density cholesterol (HDL), alkaline phosphatase (ALP), estimated glomerular filtration rate (eGFR), and type I collagen carboxy terminal peptide (S-CTX) were independent predictors for low BMD in T2D patients. The nomogram was developed from these variables using both the unadjusted area under the curve (AUC) and the bootstrap-corrected AUC (0.828). Calibration plots and the goodness-of-fit test demonstrated that the nomogram was well calibrated. CONCLUSIONS: The nomogram-illustrated model can be used by clinicians to easily predict the risk of low BMD in T2D patients. Our study also revealed that common factors are independent predictors of low BMD risk. Our results provide a new strategy for the prediction, investigation, and facilitation of low BMD in T2D patients.

[Correlation between femoral offset, rotation center and leg length discrepancy after total hip arthroplasty based on digital analysis].

OBJECTIVE: CT scans combined with Mimics software were used to measure femoral offset (FO), rotation center height (RCH) and lower leg length discrepancy (LLD) following total hip arthroplasty (THA), and the relationship between FO, RCH and LLD after THA is discussed. METHODS: Retrospective analysis was performed on 40 patients with unilateral THA who met standard cases from October 2020 to June 2022. There were 21 males and 19 females, 18 patients on the left side and 22 patients on the right side, aged range from 30 to 81 years old, with an average age of (58.90 ±14.13) years old, BMI ranged from 17.3 to 31.5 kg·m-2 with an average of (25.3±3.4) kg·m-2. There were 30 cases of femoral head necrosis (Ficat type Ⅳ), 2 cases of hip osteoarthritis (Tönnis type Ⅲ), 2 cases of developmental hip dislocation combined with end-stage osteoarthritis (Crowe type Ⅲ), and 6 cases of femoral neck fracture (Garden type Ⅳ). Three-dimensional CT reconstruction of pelvis was taken preoperative and postoperative, and three-dimensional reconstruction model was established after processing by Mimics software. FO, RCH and LLD were measured on the model. The criteria for FO reconstruction were as follows:postoperative bilateral FO difference less than 5 mm;the standard for equal length of both lower limbs was as follows:postoperative LLD difference less than 5 mm. RESULTS: Bilateral FO difference was positively correlated with LLD (r=0.744, P<0.001). Chi-square test was performed between the FO reconstructed group and the non-reconstructed eccentricity group:The results showed that the isometric ratio of lower limbs in the FO reconstructed group was significantly higher than that in the FO reconstructed group (χ2=6.320, P=0.012). The bilateral RCH difference was significantly negatively correlated with LLD(r=-0.877, P<0.001). There is a linear relationship between bilateral FO difference and bilateral RCH difference and postoperative LLD, and the linear regression equation is satisfied:postoperative LLD=0.038x-0.099y+0.257(x:postoperative bilateral FO difference, y:postoperative bilateral RCH difference; Unit:cm), F=77.993, R2=0.808, P=0.009. CONCLUSION: After THA, LLD increased with the increase of FO and decreased with the increase of RCH. The effect of lower limb isometric length can be obtained more easily by reconstruction of FO. There is a linear relationship between the bilateral FO difference and the bilateral RCH difference after THA and LLD, and the regression equation can provide a theoretical reference for judging LLD.

Development of an attenuated potato virus Y mutant carrying multiple mutations in helper-component protease for cross-protection.

Tobacco (Nicotiana tabacum) is one of the major cash crops in China. Potato virus Y (PVY), a representative member of the genus Potyvirus, greatly reduces the quality and yield of tobacco leaves by inducing veinal necrosis. Mild strain-mediated cross-protection is an attractive method of controlling diseases caused by PVY. Currently, there is a lack of effective and stable attenuated PVY mutants. Potyviral helper component-protease (HC-Pro) is a likely target for the development of mild strains. Our previous studies showed that the residues lysine at positions 124 and 182 (K124 and K182) in HC-Pro were involved in PVY virulence, and the conserved KITC motif in HC-Pro was involved in aphid transmission. In this study, to improve the stability of PVY mild strains, K at position 50 (K50) in KITC motif, K124, and K182 were separately substituted with glutamic acid (E), leucine (L), and arginine (R), resulting in a triple-mutant PVY-HCELR. The mutant PVY-HCELR had attenuated virulence and did not induce leaf veinal necrosis symptoms in tobacco plants and could not be transmitted by Myzus persicae. Furthermore, PVY-HCELR mutant was genetically stable after six serial passages, and only caused mild mosaic symptoms in tobacco plants even at 90 days post inoculation. The tobacco plants cross-protected by PVY-HCELR mutant showed high resistance to the wild-type PVY. This study showed that PVY-HCELR mutant was a promising mild mutant for cross-protection to control PVY.

Low concentrations of TNF-α in vitro transform the phenotype of vascular smooth muscle cells and enhance their survival in a three-dimensional culture system.

BACKGROUND: Vascular smooth muscle cells (VSMCs) are commonly used as seed cells in tissue-engineered vascular constructions. However, their variable phenotypes and difficult to control functions pose challenges. This study aimed to overcome these obstacles using a three-dimensional culture system. METHODS: Calf VSMCs were administered tumor necrosis factor-alpha (TNF-α) before culturing in two- and three-dimensional well plates and polyglycolic acid (PGA) scaffolds, respectively. The phenotypic markers of VSMCs were detected by immunofluorescence staining and western blotting, and the proliferation and migration abilities of VSMCs were detected by CCK-8, EDU, cell counting, scratch, and Transwell assays. RESULTS: TNF-α rapidly decreased the contractile phenotypic markers and elevated the synthetic phenotypic markers of VSMCs, as well as markedly increasing the proliferation and migration ability of VSMCs under two- and three-dimensional culture conditions. CONCLUSIONS: TNF-α can rapidly induce a phenotypic shift in VSMCs and change their viability on PGA scaffolds.

Assessment of interactions between elemental carbon and metals in black carbon: Hydroxyl radical generation and glutathione depletion.

Elemental carbon (EC) and metals are two important parts of atmospheric black carbon (BC). However, little information is available regarding the interaction between them and its impacts on the reactive oxygen species (ROS) formation and physiological antioxidants depletion. In this study, we chose six most frequently detected metals (Cu(Ⅱ), Fe(Ⅲ), Mn(Ⅱ), Cr(Ⅲ), Pb(Ⅱ) and Zn(Ⅱ)) in BC and examined their interactions with EC in the ROS generation and glutathione (GSH) oxidation. Results showed that only Cu(Ⅱ) and EC synergically promoted the GSH oxidation and hydroxyl radical (•OH) generation. Other five metals had negligible effects on the GSH oxidation regardless of the presence or absence of EC. The synergistic interaction between Cu(Ⅱ) and EC could be attributed to the superior electrical conductivity of EC. In the process, EC transferred electrons from the adjacent GSH to Cu(Ⅱ) through its graphitic carbon framework to yield Cu(Ⅰ) and GSH radical. Cu(Ⅰ) further reacted with dioxygen to generate •OH, which eventually led to the oxidation of GSH. Our results revealed a new driving force inducing the ROS formation and GSH depletion as well as provided novel insights into the risk assessment of BC.

Optimal Timing of Starting Growing Rod Treatment for Early-onset Scoliosis.

BACKGROUND CONTEXT: Growing rod (GR) systems require periodical surgical intervention and may cause associated complications, as well as worsened sagittal plane deformity. Generally, the risk of complications decreases with increment in age at the time of the index surgery with GR construct placement. However, the optimal timing to begin GR treatment has not reached a consensus yet. PURPOSE: This study was performed to investigate the effect of age at the index GR surgery on the complication rates and formulate clinical guidelines for the optimal timing to begin GR treatment for EOS patients. STUDY DESIGN: Kaplan-Meier analysis was used to determine complication occurrence as a function of the age at the index surgery and to determine the survival rates for the procedures. The receiver operator characteristic (ROC) curve was used to determine optimal cut-off values for the optimal timing of index surgery based on whether complication occurred or not. PATIENT SAMPLE: 54 patients who met the criteria were enrolled in this study. OUTCOME MEASURES: The following spinal parameters were measured: major coronal Cobb angle, global kyphosis (GK), and coronal balance (CB). CB was defined as the horizontal distance from the C7 plumb line to the center sacral vertical line. METHODS: All patients had completed GR treatment and had a minimum 1-year follow-up duration after the final surgical intervention. Patient data were collected as follows: age at the index surgery, gender, diagnosis, type of GR construct, and the number of lengthening procedures. The standing full-spine radiographs were obtained before and after the index surgery, before and after each lengthening procedures, before and after the final surgical intervention, and at the latest follow-up. Complications were categorized as implant, alignment, and general. RESULTS: Kaplan-Meier analysis of complications demonstrated a declining trend in complication rates with increasing age at the index surgery. The absence of perioperative complications was targeted, we constructed the ROC curve and the cut-off value was 71.0 months. Age at the index surgery was therefore categorized into two groups: younger-age group (≤ 71.0 months) and advanced-age group (> 71.0 months). There was a higher complication rate for the younger-age group than versus the advanced-age group (61.5% vs 22.0%, P=0.011). PJK as a major alignment-related complication, was more frequent in the younger-age group than in the advanced-age group (30.8% vs 4.9%, P=0.025). But the advanced-age group exhibited significantly more severe deformities before GR surgery compared to the younger-age group. CONCLUSIONS: This study shows that the elevated risk of complications observed in the younger-age group, which can be attributed to the younger age at the index surgery and the increased number of lengthening procedures during treatment. We suggest deferring the initiation of GR treatment until after the age of six years for EOS patients. We hope it will serve as a basis for GR technique in the treatment of EOS, with the ultimate goal of enhancing treatment outcomes for this challenging disorder.

Association between vertebral endplate defects and patient-reported symptoms: an immunohistochemical study investigating the COX-2/PGE-2/EP-4 axis.

BACKGROUND CONTEXT: Vertebral endplate defects are often implicated in degenerative disc disorders, yet their connection to patient-reported symptoms remains unclear. COX-2 and PGE-2 are known for their roles in inflammation and pain, with EP-4 receptor involvement in pain signaling. Examining their expression in vertebral endplate tissues may provide insights into pathomechanism of low back pain. PURPOSE: To investigate the association between endplate defects and patient-reported symptoms and to further clarify the role of the COX-2/PGE-2/EP-4 axis in the pathogenesis of chronic low back pain. STUDY DESIGN/SETTING: Retrospective study. PATIENT SAMPLE: A total of 71 patients who had undergone single-level L4/5 or L5/S1 modified laminectomy decompression preserving proximal upper laminae and transforaminal lumbar interbody fusion surgery were included in this study, including 18 patients diagnosed with lumbar disc herniation, 19 with lumbar disc herniation accompanied by degenerative lumbar spinal stenosis, and 34 with degenerative spondylolisthesis. OUTCOME MEASURES: Demographic data, Pfirrmann grade, Modic changes, endplate defect score, visual analog scale (VAS) for back and leg pain, and Oswestry Disability Index (ODI) before surgery, 3-month and 6-month follow-up, and the percentage of immune-positive cells (COX-2, PGE-2, and EP-4) in endplate tissue sections. METHODS: Patients were divided into defect and non-defect groups according to endplate morphology on lumbar MR. All intraoperative endplate specimens were immediately fixed in 10% formaldehyde, and then embedded in paraffin 3 days later for tissue sections. The outcome measures were compared between the defect group and non-defect group. Data were analyzed using independent t-tests and χ² tests. Pearson's rank correlation test was used to assess correlations between patient-reported symptoms and the percentage of immune-positive cells in the groups. Multivariable logistic regression models using the forward stepwise likelihood ratio method were used to identify the factors that were independently associated with endplate defects. RESULTS: The age of Defect group was significantly higher than that of non-defect group (52.5±7.7 vs. 57.2±9.1. p=.024). There were no significant differences in gender, diagnosis, BMI, comorbidities, or surgical level between the two groups. Modic changes (Type Ⅱ/Type Ⅲ) were more common in patients of Defect group than non-defect group (38.5% vs. 11.1%, p<.001), and so was disc degeneration (Pfirrmann grade Ⅳ/Ⅴ) (69.2% vs. 33.3%, p<.001). Defect group had significantly higher VAS-Back (6.5±2.0 vs. 4.9±1.6, p<.001) and ODI scores (62.9±10.7 vs. 45.2±14.8, p<.001) than non-defect group, while there was no significant differences between the two groups during the 3 and 6-month follow-up after surgery. Histologically, Defect group was characterized by upregulation of COX-2, PGE-2, and EP-4 in endplate tissue sections. Both in defect and non-defect groups, VAS-Back showed moderate positive correlations with the expressions of COX-2 (r=0.643; r=0.558, p both<0.001), PGE-2 (r=0.611; r=0.640, p both<.001), and EP-4 (r=0.643; r=0.563, p both<.001). Multivariate regression analyses reveled that percentage of COX-2-positive cells was associated with endplate defects (OR=1.509, 95%CI [1.048-2.171], p=0.027), as well as percentage of PGE-2-positive (OR=1.291, 95%CI [1.106-1.508], p=.001) and EP-4-positive cells (OR=1.284, 95%CI [1.048∼2.171], p=.003). CONCLUSIONS: Patients with endplate defects had worse quality of life, more severe disc degeneration and Modic changes, and up-regulated COX-2/PGE-2/EP-4 axis expression in cartilage endplates in patients with defected endplates. Inflammatory factors may significantly contribute to the onset and progression of chronic low back pain in patients with endplate defects, consequently impacting patient-reported symptoms.

The association between albumin-corrected calcium and prognosis in patients with cardiac arrest: a retrospective study based on the MIMIC-IV database.

BACKGROUND: Cardiac arrest (CA) is one of the leading causes of death globally, characterized by high incidence and mortality. It is of particular significance to determine the prognosis of patients with CA early and accurately. Therefore, we aim to investigate the correlation between albumin-corrected calcium (ACC) and the prognosis in patients diagnosed with CA. METHODS: We retrospectively collected data from medical information mart for intensive care IV database. Patients were divided into two groups (survival and non-survival groups), according to the 90-day prognosis. In the Restricted cubic spline (RCS) analysis, the cut-off values (8.86 and 10.32) were obtained to categorize patients into three groups: low ACC group (< 8.86), moderate ACC group (8.86-10.32), and high ACC group (> 10.32). The least absolute shrinkage and selection operator with a ten-fold cross-validation regression analysis was performed to identify variables linked to the mortality. The inverse probability treatment weighting (IPTW) was used to address the confounding factors, and a weighted cohort was generated. RCS, Kaplan-Meier curve, and Cox regression analyses were used to explore the relationship between ACC and the mortality. Sensitivity analysis was employed to validate the stability of the results. RESULTS: Cut-off values for ACC of 8.86 and 10.32 were determined. RCS analyses showed that there was an overall non-linear trend relationship between ACC and the risk of 90-day and 360-day mortalities. After IPTW adjustment, compared to the moderate ACC group, the 90-day and 360-day mortalities in the high ACC group were higher (P < 0.05). The Cox analyses before and after IPTW adjustment showed that both low ACC and high ACC group were independent risk factors for 90-day and 360-day all-cause mortality in patients with CA (P < 0.05). The results obtained from sensitivity analyses indicated the stability of the findings. The Kaplan-Meier survival curves indicated that 90- and 360-day cumulative survival rates in the low ACC and high ACC groups were lower than that in the moderate ACC group (χ2 = 11.350, P = 0.003; χ2 = 14.110, P = 0.001). CONCLUSION: Both low ACC (< 8.86) and high ACC groups (> 10.32) were independent risk factors for 90-day and 360-day all-cause mortality in patients with CA (P < 0.05). For those CA patients with high and low ACC, it deserved the attention of clinicians.

Carrageenan maintains the contractile phenotype of vascular smooth muscle cells by increasing macromolecular crowding in vitro.

BACKGROUND: The contractile phenotype of vascular smooth muscle cells (VSMCs) results in good diastolic and contractile capacities, and its altered function is the main pathophysiological basis for diseases such as hypertension. VSMCs exist as a synthetic phenotype in vitro, making it challenging to maintain a contractile phenotype for research. It is widely recognized that the common medium in vitro is significantly less crowded than in the in vivo environment. Additionally, VSMCs have a heightened sense for detecting changes in medium crowding. However, it is unclear whether macromolecular crowding (MMC) helps maintain the VSMCs contractile phenotype. PURPOSE: This study aimed to explore the phenotypic, behavioral and gene expression changes of VSMCs after increasing the crowding degree by adding carrageenan (CR). METHODS: The degree of medium crowding was examined by a dynamic light scattering assay; VSMCs survival and activity were examined by calcein/PI cell activity and toxicity and CCK-8 assays; VSMCs phenotypes and migration were examined by WB and wound healing assays; and gene expression was examined by transcriptomic analysis and RT-qPCR. RESULTS: Notably, 225 µg/mL CR significantly increased the crowding degree of the medium and did not affect cell survival. Simultaneously, CR significantly promoted the contraction phenotypic marker expression in VSMCs, shortened cell length, decreased cell proliferation, and inhibited cell migration. CR significantly altered gene expression in VSMCs. Specifically, 856 genes were upregulated and 1207 genes were downregulated. These alterations primarily affect the cellular ion channel transport, microtubule movement, respiratory metabolism, amino acid transport, and extracellular matrix synthesis. The upregulated genes were primarily involved in the cytoskeleton and contraction processes of VSMCs, whereas the downregulated genes were mainly involved in extracellular matrix synthesis. CONCLUSIONS: The in vitro study showed that VSMCs can maintain the contractile phenotype by sensing changes in the crowding of the culture environment, which can be maintained by adding CR.

Interfacial charge transfer in sheet Ni2P-FePx heterojunction to promote the study of electrocatalytic oxygen evolution.

The substantial expense associated with catalysts significantly hampers the progress of electrolytic water-based hydrogen production technology. There is an urgent need to find non-precious metal catalysts that are both cost-effective and highly efficient. Here, the porous Ni2P-FePx nanomaterials were successfully prepared by hydrothermal method, nickel foam as the base, iron nitrate solution as the caustic agent and iron source, and finally phosphating at low temperature. The obtained porous Ni2P-FePx nanosheets showed excellent catalytic activity under alkaline PH = 14, and an overpotential of merely 241 mV was required to achieve a current density of 50 mA cm-2. The morphology of the nanosheet can still be flawlessly presented on the screen after 50 h of working at high current density.

Hyperforin ameliorates neuroinflammation and white matter lesions by regulating microglial VEGFR2 /SRC pathway in vascular cognitive impairment mice.

AIM: To explore the neuroprotective potential of hyperforin and elucidate its underlying molecular mechanisms involved in its therapeutic effects against vascular cognitive impairment (VCI). METHODS: The active compounds and possible targets of Hypericum perforatum L. that may be effective against VCI were found by network pharmacology in this research. We utilized bilateral common carotid artery occlusion (BCCAO) surgery to induce a VCI mouse model. Morris water maze (MWM) and Y-maze tests were used to assess VCI mice's cognitive abilities following treatment with hyperforin. To evaluate white matter lesions (WMLs), we utilized Luxol fast blue (LFB) stain and immunofluorescence (IF). Neuroinflammation was assessed using IF, western blot (WB), and enzyme-linked immunosorbent assay (ELISA). The effects of hyperforin on microglia were investigated by subjecting the BV2 microglial cell line to oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The expressions of VEGFR2 , p-SRC, SRC, VEGFA, and inflammatory markers including IL-10, IL-1ß, TNF-α, and IL-6 were subsequently assessed. RESULTS: The VEGFR2 /SRC signaling pathway is essential for mediating the protective properties of hyperforin against VCI according to network pharmacology analysis. In vivo findings demonstrated that hyperforin effectively improved BCCAO-induced cognitive impairment. Furthermore, staining results showed that hyperforin attenuated WMLs and reduced microglial activation in VCI mice. The hyperforin treatment group's ELISA results revealed a substantial decrease in IL-1ß, IL-6, and TNF-α levels. According to the results of in vitro experiments, hyperforin decreased the release of pro-inflammatory mediators (TNF-α, IL-6, and IL-1ß) and blocked microglial M1-polarization by modulating the VEGFR2 /SRC signaling pathway. CONCLUSION: Hyperforin effectively modulated microglial M1 polarization and neuroinflammation by inhibiting the VEGFR2 /SRC signaling pathways, thereby ameliorating WMLs and cognitive impairment in VCI mice.

Seeing Your Stories: Visualization for Narrative Medicine.

Importance: Narrative medicine (NM), in which patient stories play a crucial role in their diagnosis and treatment, can potentially support a more holistic approach to patient care than traditional scientific ones. However, there are some challenges in the implementation of narrative medicine, for example, differences in understanding illnesses between physicians and patients and physicians' increased workloads and overloaded schedules. This paper first presents a review to explore previous visualization research for narrative medicine to bridge the gap between visualization researchers and narrative medicine experts and explore further visualization opportunities. Highlights: The review is conducted from 2 perspectives: (a) the contexts and domains in which visualization has been explored for narrative medicine and (b) the forms and solutions applied in these studies. Four applied domains are defined, including understanding patients from narrative records, medical communication, medical conversation training in education, and psychotherapy and emotional wellness enhancement. Conclusions: A future work framework illustrates some opportunities for future research, including groups of specific directions and future points for the 4 domains and 3 technological exploration opportunities (combination of narrative and medical data visualization, task-audience-based visual storytelling, and user-centered interactive visualization). Specifically, 3 directions of future work in medical communication (asynchronous online physician-patient communication, synchronous face-to-face medical conversation, and medical knowledge dissemination) were concluded.

miR-101-3p-mediated role of PDZK1 in hepatocellular carcinoma progression and the underlying PI3K/Akt signaling mechanism.

BACKGROUND: The molecular targets and associated mechanisms of hepatocellular carcinoma (HCC) have been widely studied, but the roles of PDZK1 in HCC are unclear. Therefore, the aim of this study is to explore the role and associated mechanisms of PDZK1 in HCC. RESULTS: It was found that the expression of PDZK1 in HCC tissues was higher than that in paired paracancerous tissues. High expression of PDZK1 was associated with lymph node metastasis, degree of differentiation, and clinical stage. Upregulation of PDZK1 in HCC cells affected their proliferation, migration, invasion, apoptosis, and cell cycle, and also induced PI3K/AKT activation. PDZK1 is a downstream target gene of miR-101-3p. Accordingly, increase in the expression of miR-101-3p reversed the promotive effect of PDZK1 in HCC. Moreover, PDZK1 was found to accelerate cell proliferation and promote the malignant progression of HCC via the PI3K/AKT pathway. CONCLUSION: Our study indicated that the miR-101-3p/PDZK1 axis plays a role in HCC progression and could be beneficial as a novel biomarker and new therapeutic target for HCC treatment.

Light-Induced Dynamic Manipulation of Liquid Metal Droplets in the Ambient Atmosphere.

Dynamic manipulation of liquid metal (LM) droplets, a material combining metallicity and fluidity, has recently revealed tremendous potential in developing unconstrained microrobots. LM manipulating techniques based on magnetic fields, electric fields, chemical reactions, and ion concentration gradients in liquid environments have advanced considerably, but dynamic manipulation in air remains a challenge. Herein, a photoresponsive pyroelectric superhydrophobic (PPS) platform is proposed for noncontact, flexible, and controllable manipulation in the ambient atmosphere. The PPS can generate additional free charges when illuminated by light, thus generating the driving force to manipulate liquid metal droplets. By using the synergistic effect of dielectrophoretic and electrostatic forces generated under light navigation, liquid metal droplets can achieve a series of complex motion behaviors, such as climbing slopes, going over steps, avoiding obstacles, crossing mazes, etc. We further extend the light control of liquid metal droplets to robots applied in electronic circuits, including circuit switching robots and circuit welding robots. This light strategy for manipulating liquid metal droplets provides insights into the development of intelligent, responsive interfaces and simultaneously provides possibilities for the application of liquid metals.

DNA damage-regulated autophagy modulator 1 prevents glioblastoma cells proliferation by regulating lysosomal function and autophagic flux stability.

Glioblastoma (GBM) is the most aggressive and life-threatening brain tumor, characterized by its highly malignant and recurrent nature. DNA damage-regulated autophagy modulator 1 (DRAM-1) is a p53 target gene encoding a lysosomal protein that induces macro-autophagy and damage-induced programmed cell death in tumor growth. However, the precise mechanisms underlying how DRAM-1 affects tumor cell proliferation through regulation of lysosomal function and autophagic flux stability remain incompletely understood. We found that DRAM-1 expressions were evidently down-regulated in high-grade glioma and recurrent GBM tissues. The upregulation of DRAM-1 could increase mortality of primary cultured GBM cells. TEM analysis revealed an augmented accumulation of aberrant lysosomes in DRAM-1-overexpressing GBM cells. The assay for lysosomal pH and stability also demonstrated decreasing lysosomal membrane permeabilization (LMP) and impaired lysosomal acidity. Further research revealed the detrimental impact of lysosomal dysfunction, which impaired the autophagic flux stability and ultimately led to GBM cell death. Moreover, downregulation of mTOR phosphorylation was observed in GBM cells following upregulation of DRAM-1. In vivo and in vitro experiments additionally illustrated that the mTOR inhibitor rapamycin increased GBM cell mortality and exhibited an enhanced antitumor effect.

Engineering and application of LacI mutants with stringent expressions.

Optimal transcriptional regulatory circuits are expected to exhibit stringent control, maintaining silence in the absence of inducers while exhibiting a broad induction dynamic range upon the addition of effectors. In the Plac /LacI pair, the promoter of the lac operon in Escherichia coli is characterized by its leakiness, attributed to the moderate affinity of LacI for its operator target. In response to this limitation, the LacI regulatory protein underwent engineering to enhance its regulatory properties. The M7 mutant, carrying I79T and N246S mutations, resulted in the lac promoter displaying approximately 95% less leaky expression and a broader induction dynamic range compared to the wild-type LacI. An in-depth analysis of each mutation revealed distinct regulatory profiles. In contrast to the wild-type LacI, the M7 mutant exhibited a tighter binding to the operator sequence, as evidenced by surface plasmon resonance studies. Leveraging the capabilities of the M7 mutant, a high-value sugar biosensor was constructed. This biosensor facilitated the selection of mutant galactosidases with approximately a seven-fold improvement in specific activity for transgalactosylation. Consequently, this advancement enabled enhanced biosynthesis of galacto-oligosaccharides (GOS).

The associations between peripheral inflammatory and lipid parameters, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events.

BACKGROUND: The global prevalence of VCI has increased steadily in recent years, but diagnostic biomarkers for VCI in patients with non-disabling ischemic cerebrovascular incidents (NICE) remain indefinite. The primary objective of this research was to investigate the relationship between peripheral serological markers, white matter damage, and cognitive function in individuals with NICE. METHODS: We collected clinical data, demographic information, and medical history from 257 patients with NICE. Using the MoCA upon admission, patients were categorized into either normal cognitive function (NCF) or VCI groups. Furthermore, they were classified as having mild white matter hyperintensity (mWMH) or severe WMH based on Fazekas scores. We then compared the levels of serological markers between the cognitive function groups and the WMH groups. RESULTS: Among 257 patients with NICE, 165 were male and 92 were female. Lymphocyte count (OR = 0.448, P < 0.001) and LDL-C/HDL-C (OR = 0.725, P = 0.028) were protective factors for cognitive function in patients with NICE. The sWMH group had a higher age and inflammation markers but a lower MoCA score, and lymphocyte count than the mWMH group. In the mWMH group, lymphocyte count (AUC = 0.765, P < 0.001) and LDL-C/HDL-C (AUC = 0.740, P < 0.001) had an acceptable diagnostic value for the diagnosis of VCI. In the sWMH group, no significant differences were found in serological markers between the NCF and VCI groups. CONCLUSION: Lymphocyte count, LDL-C/HDL-C were independent protective factors for cognitive function in patients with NICE; they can be used as potential biological markers to distinguish VCI in patients with NICE and are applicable to subgroups of patients with mWMH.