Search

Abstract Tissue-derived extracellular vesicles (EVs) are emerging as pivotal players to maintain organ homeostasis, which show promise as a next-generation candidate for medical use with extensive source. However, the detailed function and therapeutic potential of tissue EVs remain insufficiently studied. Here, through bulk and single-cell RNA sequencing analyses combined with ultrastructural tissue examinations, we first reveal that in situ liver tissue EVs (LT-EVs) contribute to the intricate liver regenerative process after partial hepatectomy (PHx), and that hepatocytes are the primary source of tissue EVs in the regenerating liver. Nanoscale and proteomic profiling further identify that the hepatocyte-specific tissue EVs (Hep-EVs) are strengthened to release with carrying proliferative messages after PHx. Moreover, targeted inhibition of Hep-EV release via AAV-shRab27a in vivo confirms that Hep-EVs are required to orchestrate liver regeneration. Mechanistically, Hep-EVs from the regenerating liver reciprocally stimulate hepatocyte proliferation by promoting cell cycle progression through Cyclin-dependent kinase 1 (Cdk1) activity. Notably, supplementing with Hep-EVs from the regenerating liver demonstrates translational potential and ameliorates insufficient liver regeneration. This study provides a functional and mechanistic framework showing that the release of regenerative Hep-EVs governs rapid liver regeneration, thereby enriching our understanding of physiological and endogenous tissue EVs in organ regeneration and therapy.

Abstract Background In recent decades, early rehabilitation after Achilles tendon rupture (ATR) repair has been proposed. The aim of this prospective cohort study was to compare different immobilisation durations in order to determine the optimal duration after open surgery for ATR repair. Methods This study included 1088 patients (mean age, 34.9 ± 5.9 years) who underwent open surgery for acute ATR repair. The patients were categorised into four groups (A, B, C, and D) according to postoperative immobilisation durations of 0, 2, 4, and 6 weeks, respectively. All patients received the same suture technique and a similar rehabilitation protocol after brace removal,; they were clinically examined at 2, 4, 6, 8, 10, 12, 14, and 16 weeks postoperatively, with a final follow-up at a mean of 19.0 months. The primary outcome was the recovery time for the one-leg heel-rise height (OHRH). Secondary outcomes included the time required to return to light exercise (LE) and the recovery times for the range of motion (ROM). Data regarding the surgical duration, complications, the visual analogue scale (VAS) score for pain, the Achilles tendon Total Rupture Score (ATRS), and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale score were also collected. Results The recovery times for OHRH, LE, and ROM were significantly shorter in groups A and B than in groups C and D (P

Abstract Background Aging is a multifaceted process that affects all organ systems. With the increasing trend of population aging, aging-related diseases have resulted in significant medical challenges and socioeconomic burdens. Mesenchymal stromal cells (MSCs), due to their antioxidative stress, immunoregulatory, and tissue repair capabilities, hold promise as a potential anti-aging intervention. Methods In this study, we transplanted MSCs into naturally aged rats at 24 months, and subsequently examined levels of aging-related factors such as β-galactosidase, superoxide dismutase, p16, p21 and malondialdehyde in multiple organs. Additionally, we assessed various aging-related phenotypes in these aged rats, including immune senescence, lipid deposition, myocardial fibrosis, and tissue damage. We also conducted a 16 S ribosomal ribonucleic acid (rRNA) analysis to study the composition of gut microbiota. Results The results indicated that MSCs significantly reduced the levels of aging-associated and oxidative stress-related factors in multiple organs such as the heart, liver, and lungs of naturally aging rats. Furthermore, they mitigated chronic tissue damage and inflammation caused by aging, reduced levels of liver lipid deposition and myocardial fibrosis, alleviated aging-associated immunodeficiency and immune cell apoptosis, and positively influenced the gut microbiota composition towards a more youthful state. This research underscores the diverse anti-aging effects of MSCs, including oxidative stress reduction, tissue repair, metabolic regulation, and improvement of immune functions, shedding light on the underlying anti-aging mechanisms associated with MSCs. Conclusions The study confirms that MSCs hold great promise as a potential anti-aging approach, offering the possibility of extending lifespan and improving the quality of life in the elderly population.

Abstract Background Multidrug-resistant organisms (MDRO) pose a significant threat to public health. Intensive Care Units (ICU), characterized by the extensive use of antimicrobial agents and a high prevalence of bacterial resistance, are hotspots for MDRO proliferation. Timely identification of patients at high risk for MDRO can aid in curbing transmission, enhancing patient outcomes, and maintaining the cleanliness of the ICU environment. This study focused on developing a machine learning (ML) model to identify patients at risk of MDRO during the initial phase of their ICU stay. Methods Utilizing patient data from the First Medical Center of the People’s Liberation Army General Hospital (PLAGH-ICU) and the Medical Information Mart for Intensive Care (MIMIC-IV), the study analyzed variables within 24 h of ICU admission. Machine learning algorithms were applied to these datasets, emphasizing the early detection of MDRO colonization or infection. Model efficacy was evaluated by the area under the receiver operating characteristics curve (AUROC), alongside internal and external validation sets. Results The study evaluated 3,536 patients in PLAGH-ICU and 34,923 in MIMIC-IV, revealing MDRO prevalence of 11.96% and 8.81%, respectively. Significant differences in ICU and hospital stays, along with mortality rates, were observed between MDRO positive and negative patients. In the temporal validation, the PLAGH-ICU model achieved an AUROC of 0.786 [0.748, 0.825], while the MIMIC-IV model reached 0.744 [0.723, 0.766]. External validation demonstrated reduced model performance across different datasets. Key predictors included biochemical markers and the duration of pre-ICU hospital stay. Conclusions The ML models developed in this study demonstrated their capability in early identification of MDRO risks in ICU patients. Continuous refinement and validation in varied clinical contexts remain essential for future applications.

ABSTRACTThe sweet aromas of red jujube extracts and caramel products are similar, and their reactions could bring synergistic flavors. However, the reaction conditions and the characteristic flavor compounds involved are not well known. In this study, the Maillard reaction was performed using red jujube extracts and glucose caramel products. The reaction factors, such as reaction temperature, reaction time, initial pH, and sample-to-solvent ratio, were optimized by the analysis of sensory scores, total flavor compound (TFC) content, and UV absorption at 420 nm. The optimization of the above factors was further performed by response surface methodology, and antioxidant activities were investigated. Single-factor optimization suggested that the preferred conditions for the Maillard reaction were a temperature of 120°C, a reaction duration of 80 min, an initial pH of 8.0, and a sample-to-solvent ratio of 7:1 (jujube extract: caramel product = 7:1). According to the response surface model, the influence of four factors on the TFC content decreased in the following order: reaction temperature > reaction time > sample-to-solvent ratio > initial pH. The optimal conditions were further established according to the response surface model. GC-MS analysis suggested that the TFC content of Maillard products under the optimized conditions increased by 30.8% compared with those of the unreacted samples. The characteristic flavor compounds in the Maillard products were furfuryl alcohol, 3,5-dihydroxy-2-methyl-4H-pyran-4-one (DDMP), and 5-hydroxymethylfurfural (5-HMF), with the contents of 44.68, 176.26, and 139.75 µg/g, respectively. Moreover, the reaction products exhibited potent antioxidant effects.

This study explored the factors influencing cooperative innovation in environmentally friendly agricultural biotechnology in China. First, we constructed an evolutionary game model comprising the factors of net income of cooperative innovation, net income of independent innovation, market constraints, and government subsidies. Using MATLAB simulation, we assigned different values to the aforementioned variables to explore the evolutionary trend of innovators’ willingness to cooperate. Results showed that when the values of net income of cooperative innovation, net income of independent innovation, market constraints, and government subsidies exceeded the threshold, innovators’ willingness to cooperate was significantly enhanced. Furthermore, the proportion of innovators who cooperated with others gradually increased to 100%; otherwise, it gradually decreased to 0%. Comparing the simulation curve with the real evolution curve of cooperative innovation in agricultural biotechnology in China, we found that the gradual decline in the willingness to cooperate could be due to insufficient subsidies for cooperative innovation, low income from cooperative innovation, weak profitability of innovators, and weak market constraints.

Although characterized by high reactive oxygen species (ROS) generation, cancer cells maintain redox homeostasis to avoid severe damage (e.g., DNA, protein, and plasma membrane dysfunction) and facilitate cancer progression. Emerging evidence has indicated that targeting the regulation of redox homeostasis to amplify oxidative stress is of value in cancer therapy. However, therapeutic agents like nucleic acids, small molecular inhibitors, and chemotherapeutic drugs fail to exert effective cancer inhibition due to their low bioavailability, susceptibility to serum enzymes, and inefficiency in cell membrane penetrating. Therefore, specific delivery vectors are required to facilitate the intracellular delivery of anti-tumor drugs. In the past few decades, various engineered nanomaterials have been designed and developed for drug delivery. In particular, rational nanoparticles (NPs) have garnered more attention due to their splendid long circulation ability, modification capacity, and stimulation-responded release. In this review, the methods of ROS generation and ROS-regulated signaling in cancer development were firstly briefly introduced. The anti-oxidant system, including the metabolism shifting and anti-oxidant genes, were next reviewed, and the strategies of NPs-mediated targeted regulation of redox homeostasis were emphatically discussed. The main strategies include NPs-induced delivery of nucleic acids, small molecule inhibitors, chemotherapeutic agents, radiosensitizers, and NPs-induced ROS generation and GSH depletion. The future development of NP-mediated redox dyshomeostasis in cancer therapy and their challenges in clinical translation were finally discussed.

Indoor location services often use Bluetooth low energy (BLE) devices for their low energy consumption and easy implementation. Applications like device monitoring, ranging, and asset tracking utilize the received signal strength (RSS) of the BLE signal to estimate the proximity of a device from the receiver. However, in multipath environments, RSS-based solutions may not provide an accurate estimation. In such environments, receivers with antenna arrays are used to calculate the difference in time of flight (ToF) and therefore calculate the direction of arrival (DoA) of the Bluetooth signal. Other techniques like triangulation have also been used, such as having multiple transmitters or receivers as a network of sensors. To find a lost item, devices like Tile© use an onboard beeper to notify users of their presence. In this paper, we present a system that uses a single-measurement device and describe the method of measurement to estimate the location of a BLE device using RSS. A BLE device is configured as an Eddystone beacon for periodic transmission of advertising packets with RSS information. We developed a smartphone application to read RSS information from the beacon, designed an algorithm to estimate the DoA, and used the phone’s internal sensors to evaluate the DoA with respect to true north. The proposed measurement method allows for asset tracking by iterative measurements that provide the direction of the beacon and take the user closer at every step. The receiver application is easily deployable on a smartphone, and the algorithm provides direction of the beacon within a 30° range, as suggested by the provided results.

Abstract DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure. Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions. Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6 (BCL6) and inhibit the expression of dynamin-related protein 1 (DRP1). When DDX17 expression is reduced, transcriptional repression of BCL6 is attenuated, leading to increased DRP1 expression and mitochondrial fission, which in turn leads to impaired mitochondrial homeostasis and heart failure. We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure. These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

Abstract Background Fractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function. Methods We collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient. Results (1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test. Conclusion FeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH.

Background To improve the performance of cannulated screws (CSs) in the treatment of femoral neck fractures (FNF), a number of new screw configurations have been proposed. However, most of the studies have only analyzed the biomechanical performance of different screw configurations under static conditions. This study aimed to investigate the biomechanical performance of three cannulated screws configurations under different loadings through finite element analysis. Methods In this FEA study, nine numerical models of proximal femur were employed to analyze the mechanical response of various fracture types and different fixation strategies (three inverted triangular parallel cannulated screws (TCS), four non-parallel cannulated screws (FCS) and biplane double-supported screw fixation (BDSF) respectively). The maximum principal strain (MPS) on the proximal femur and the von Mises stress on the screws were compared for different models. Results In Pauwels I and II fractures, FCS had the lowest peak MPS on the proximal femur and the BDSF had highest peak MPS value. In Pauwels III fractures, BDSF performance in MPS is improved and better than FCS under partial loading conditions. FCS exhibits the lowest von Mises stress in all load conditions for all fracture types, demonstrating minimal risk of screws breakage. Conclusions FCS is an ideal screw configuration for the treatment of FNF. And BDSF has shown potential in the treatment of Pauwels type III FNF.

Alzheimer’s disease (AD) is increasingly recognized as being intertwined with the dysregulation of lipid metabolism. Lipids are a significant class of nutrients vital to all organisms, playing crucial roles in cellular structure, energy storage, and signaling. Alterations in the levels of various lipids in AD brains and dysregulation of lipid pathways and transportation have been implicated in AD pathogenesis. Clinically, evidence for a high-fat diet firmly links disrupted lipid metabolism to the pathogenesis and progression of AD, although contradictory findings warrant further exploration. In view of the significance of various lipids in brain physiology, the discovery of complex and diverse mechanisms that connect lipid metabolism with AD-related pathophysiology will bring new hope for patients with AD, underscoring the importance of lipid metabolism in AD pathophysiology, and promising targets for therapeutic intervention. Specifically, cholesterol, sphingolipids, and fatty acids have been shown to influence amyloid-beta (Aβ) accumulation and tau hyperphosphorylation, which are hallmarks of AD pathology. Recent studies have highlighted the potential therapeutic targets within lipid metabolism, such as enhancing apolipoprotein E lipidation, activating liver X receptors and retinoid X receptors, and modulating peroxisome proliferator-activated receptors. Ongoing clinical trials are investigating the efficacy of these strategies, including the use of ketogenic diets, statin therapy, and novel compounds like NE3107. The implications of these findings suggest that targeting lipid metabolism could offer new avenues for the treatment and management of AD. By concentrating on alterations in lipid metabolism within the central nervous system and their contribution to AD development, this review aims to shed light on novel research directions and treatment approaches for combating AD, offering hope for the development of more effective management strategies.

Ray parenchyma cells are involved in the initiation of heartwood formation. The position within a ray influences the timing of ray parenchyma cell differentiation and function; however, there is little information concerning the positional influence on the cellular changes of ray parenchyma cells from sapwood and heartwood. In this study, radial variations in morphology, size, and ultrastructure of ray parenchyma cells were studied by combined transmission electron microscopy and optical microscopy. Results showed that cellular traits of ray parenchyma cells in Populus tomentosa were all affected by both radial position in the secondary xylem and position within a ray. Specifically, radial variations in cellular traits were more evident in isolation cells, which were not adjacent to vessel elements. Both cell length and cell width/length ratio of isolation cells were bigger than contact cells, which contacted adjacent vessel elements via pits. Moreover, the secondary wall thickening and lignification of contact cells developed in the current-year xylem, much earlier than isolation cells. Secondary walls in contact cells were in a polylamellate structure with a protective layer on the inner side. No alteration in the ultrastructure of contact cells occurred in the sapwood-heartwood transition zone, except that most contact cells died. By contrast, in the transition zone, isolation cells still lived. A thin secondary wall began to deposit on the thick primary wall of isolation cells, with two isotropic layers on the inner side of the primary wall and secondary wall respectively being characteristic. Meanwhile, starch grains in isolation cells were depleted, and dark polyphenolic droplets lost their spherical shape and flowed together. Furthermore, the intercellular spaces of isolation cells became densified in the transition zone. Overall, cellular changes suggested that the positional information of ray parenchyma cells appeared to be an important factor in the transformation from sapwood to heartwood. Unlike contact cells, isolation cells were more elongated, specialized in radial transport, had a delayed formation of secondary walls, and were involved in the synthesis of heartwood substances. Our result promotes the elucidation of the involvement of xylem rays in heartwood formation.

IntroductionNeuromyelitis Optica spectrum disorder (NMOSD) is an autoimmune disease characterized by anti-aquaporin-4 (AQP4) auto-antibodies. The discovery of antibodies AQP4 and myelin oligodendrocyte glycoprotein (MOG) has expanded our understanding of the pathogenesis of neuromyelitis optica. However, the molecular mechanisms underlying the disease, particularly AQP4-associated optic neuritis (AQP4-ON), remain to be fully elucidated.MethodsIn this study, we utilized Weighted Gene Co-expression Network Analysis (WGCNA) to investigate the transcriptomic profiles of peripheral blood samples from patients with AQP4-ON and MOG-positive optic neuritis (MOG-ON), compared to healthy controls.ResultsWGCNA revealed a brown module (ME brown) strongly associated with AQP4-ON, which correlated positively with post-onset visual acuity decline. A total of 132 critical genes were identified, mainly involved in histone modification and microtubule dynamics. Notably, genes HDAC4, HDAC7, KDM6A, and KDM5C demonstrated high AUC values in ROC analysis, indicating their potential as biomarkers for AQP4-ON.ConclusionOur findings provide novel insights into the molecular signature of AQP4-ON and highlight the potential of systems biology approaches in identifying biomarkers for NMOSD. The identified histone modification genes warrant further investigation for their role in disease pathogenesis and as therapeutic targets.

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

Topological boundary modes, which are localized at the edge of topological materials, have received significant attention for their various applications in robust waveguides, optical cavities, and topological lasers. To envision their further applications in tunable devices, we propose and demonstrate a scheme to dynamically manipulate topological boundary modes by exploiting the two translation parameters of photonic crystals. We find that the translation not only transports the Wannier state similar to conventional Thouless pumping but also induces a nonzero Chern number in the two-dimensional synthetic space while preserving the time-reversal symmetry in the real space. Through changing the translation, gapless and tunable topological boundary modes are demonstrated. As a specific application, we show a dynamic bandpass filter with real-time tuning over 100% bandgap, a capability that cannot be achieved with only one translation parameter. Our design opens a venue for the development of tunable topological devices based on synthetic parameter dimension and can be generalized to other bosonic systems.

BackgroundElectronic mental health literacy (eMHL) is critical for accessing and effectively using digital mental health resources. However, there is a paucity of research on how eMHL varies across age groups. ObjectiveThis study aimed to investigate differences in eMHL among young, middle-aged, and older adults; provide insights into the needs, behaviors, and attitudes of different age groups in relation to digital mental health resources; and ultimately, inform the improvement of mental health services. MethodsA qualitative investigation was conducted to examine the differences in eMHL across different age demographics in the Chinese population in 2023. The study sample comprised 3 distinct age groups: 18-34 years, 35-64 years, and 65 years and older. Participants were recruited through purposive sampling to ensure a diverse representation of the population. Data were collected through semistructured one-on-one interviews, which allowed for in-depth exploration of individual experiences and perceptions. The gathered data were subsequently subjected to rigorous thematic analysis to enable the identification and interpretation of recurring patterns and themes. ResultsThe principal outcomes derived from these interviews were synthesized into 5 distinct dimensions: emotional needs, use of digital mental health resources, assessment of digital mental health information, engagement with social media to regulate emotions, and coping strategies. These dimensions were uniformly observed across the 3 age groups. ConclusionsWe identified differences in knowledge, skills, and attitudes regarding the use of web-based information for managing mental health problems between the 3 age groups. The findings highlight the importance of age-specific strategies for improving eMHL.

ObjectiveThis study investigated the link between triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and nonalcoholic fatty liver disease (NAFLD) and liver fibrosis in American adults.MethodsInformation for 6495 participants from the National Health and Nutrition Examination Survey (NHANES) 2017–2020.03 was used for this cross-sectional study. The link between TG/HDL-C ratios and NAFLD and liver fibrosis was assessed by multiple linear regression before evaluating nonlinear correlations based on smoothed curve fitting models. Stratification analysis was then applied to confirm whether the dependent and independent variables displayed a stable association across populations.ResultsTG/HDL-C ratios were positively correlated with NAFLD, with higher ratios being linked to increased prevalence of NAFLD. After adjusting for potential confounders, the odds ratios (OR) for NAFLD patients in the fourth TG/HDL-C quartile were 3.61 (95% confidence interval [CI], 2.94–4.38) (P for trend < 0.001) in comparison with those in the first quartile after adjusting for clinical variables. However, no statistical significance was noted for the ratio for liver fibrosis after adjusting for potential confounders (P for trend = 0.07). A nonlinear correlation between TG/HDL-C ratios and NAFLD was observed based on smoothed curve fitting models. However, a nonlinear relationship between the ratios and liver fibrosis was not established. In subgroup analyses, there was an interaction between smoking status and TG/HDL-C ratio in relation to the prevalence of liver fibrosis (P for interaction < 0.001).ConclusionsAmong American adults, the TG/HDL-C ratio was noted to be nonlinearly positively associated with the prevalence of NAFLD; however, this relationship was not present in liver fibrosis.

The interpretation model for gas saturation in deep clastic reservoirs subject to intensive extrusion stress relies predominantly on experimental petrophysical data and the expanded Archie equation. Nonetheless, these methodologies may not consistently yield optimum results. Specifically, when subsurface pressure impacts formation resistivity, the resulting curve values exhibit substantial elevations, leading to significant inaccuracies in the precise estimation of gas saturation from resistivity logging data. Consequently, the evaluation of logging interpretations becomes a complex undertaking. This paper aims to comprehensively assess gas saturation in deep clastic reservoirs from both electrical and mechanical perspectives. To achieve this goal, we employ a multifaceted approach encompassing the Archie formula, the stress-corrected variable cementation index saturation model, and the resistivity-corrected saturation model. Through rigorous theoretical analysis and the utilization of simulated experimental data, a quantitative relationship equation between resistivity and stress difference has been established. Building upon this fundamental groundwork, an innovative resistivity-corrected saturation calculation model has been proposed. In comparison to the two alternative models, the new model exhibits enhanced accuracy in calculating gas saturation, as it is less influenced by extrusion stress and gravitational compaction. Furthermore, it demonstrates better consistency with core mercury injection capillary pressure data in determining gas saturation. The findings of this research provide valuable insights for the effective evaluation of deep clastic reservoirs, offering a robust framework for advancing the understanding of gas saturation in the face of complex geological and geophysical challenges.

This study proposes a novel spoof surface plasmon polariton (SSPP) transmission line unit based on a coplanar waveguide (CPW) design. The dispersion relationship is derived from its equivalent circuit, and a low-pass notch filter is designed accordingly, operating in the frequency range of 0 GHz to 4.45 GHz, effectively blocking the transmission signal at 2.4 GHz. The filter has the advantages of a compact size, high transmission efficiency, and compact structure. The mode transition from quasi-transverse electromagnetic (TEM) waves in CPW to transverse magnetic (TM) waves in the SSPP waveguide is achieved using a centrally symmetric linear gradient groove structure. For the first time within the scope of this study, we propose a novel method for forming notch filters that involves radiating signals of selected frequencies into free space to create notch, thereby eliminating the negative effects of the reflected signals at notch point. This study achieves signal radiation at 2.4 GHz to free space, forming a notch, by loading an interdigitated coupling structure on the backside of the filter. The relationship between finger length and resonant frequency enables the reconfigurability of the filtering band. To validate the accuracy of the proposed filter, a prototype filter is fabricated and tested in this frequency range. The measurement results are consistent with the analytical results.

Abstract Objective To investigate the effect of sequential distalization on increasing gaps in the maxillary anterior teeth, focusing on the control of torque and three-dimensional teeth movement during anterior retraction with clear aligners in extraction cases. Methods We recruited 24 patients who were undergoing extraction bilateral maxillary first premolars with clear aligners. According to a predetermined increment in the spaces between the maxillary anterior teeth, the patients were divided into three groups: those with no gap (9 cases), a 0.5 mm gap (6 cases) and a 1.0 mm gap (9 cases). In each group, a 2.0 mm en-mass retraction was applied on the anterior teeth. Plaster casts of the upper full dentition were obtained both before and after a 2 mm retraction. The palatal folds were used to overlap each pair of models. The three-dimensional movement of the teeth and the change of torque for the anterior teeth were subsequently analyzed using Geomagic Studio 2014 software. Results The change in torque in the groups with added gaps was significantly smaller than that in the group with no gaps (P 0.05). In the labial-lingual and vertical directions, the displacements of the central and lateral incisors were smaller in the groups with additional gaps compared to those in the groups without gaps (P 0.05). Then, a comparison was made between the displacement of the second premolar to the second molar in the mesial-distal direction across all groups. The study revealed that the anchorage molars in the group without gaps demonstrated significantly smaller displacement compared to those in the group with additional gaps (P

As the utilization of high-resolution imaging modalities, such as ultrasound, becomes increasingly prevalent, there has been a swift rise in the detection rates of malignant thyroid nodules (MTC). Surgery remains the cornerstone of standard treatment for these nodules. However, the advent and evolution of thermal ablation (TA) techniques, encompassing radiofrequency ablation, laser ablation, and microwave ablation, have emerged as a novel therapeutic avenue for patients with MTC, particularly for those deemed unsuitable for surgery due to high risks or for those who refuse surgery. Presently, TA has been validated as an efficacious and safe intervention for both benign thyroid nodules and a subset of MTC. An expanding body of research has been dedicated to broadening the applicability of TA, initially from recurrent thyroid cancer and lymph nodes to now encompass isolated papillary thyroid microcarcinomas (PTMC) alongside a comprehensive exploration into the expanded parameters such as size, number, and location of PTMC, and its applicability in other types of thyroid cancer. This review provides a detailed synthesis of the clinical evidence about the use of TA in the management of MTC, as endorsed by current guidelines. It further delves into the ongoing research efforts aimed at extending its indications and discusses the prospective implications and challenges of integrating TA into the clinical management paradigms for MTC.

AbstractBackground Cuproptosis, a type of cell death involving copper ion accumulation and oxidative stress, has been implicated in the development of Alzheimer’s disease (AD).Aim This study aimed to explore the potential mechanisms and roles of cuproptosis-related genes (CRGs), long non-coding RNAs (lncRNAs), and immune cells in the development of cuproptosis in AD.Subjects and methods Gene expression profiles of AD were acquired from the Gene Expression Omnibus (GEO) database, and differential analysis was conducted to identify CRGs. Random Forest (RF) modelling was employed to select the most crucial CRGs, which were subsequently validated in the test set. A nomogram model was created to predict AD risk and categorise AD subtypes based on the identified CRGs. A lncRNA-related ceRNA network was built, and immune cell infiltration analysis was conducted.Results Twelve differentially expressed CRGs were identified in the AD dataset. The RF model pinpointed the five most critical CRGs, which were validated in the test set with an AUC of 0.90. A lncRNA-related ceRNA network was developed, and immune cell infiltration analysis revealed high levels of M1 macrophages and mast cells, along with low levels of memory B cells in AD samples. Correlation analysis unveiled associations between CRGs, lncRNAs, and differentially infiltrating immune cells.Conclusion This research offers insights into the potential mechanisms and roles of CRGs, lncRNAs, and immune cells in the development of cuproptosis in AD. The identified CRGs and lncRNAs may serve as potential therapeutic targets for AD, and the nomogram model may assist in early AD diagnosis and subtyping.

In the contemporary epoch, cancer stands as the predominant cause of premature global mortality, necessitating a focused exploration of molecular markers and advanced therapeutic strategies. N6-methyladenosine (m6A), the most prevalent mRNA modification, undergoes dynamic regulation by enzymes referred to as methyltransferases (writers), demethylases (erasers), and effective proteins (readers). Despite lacking methylation activity, RNA-binding motif protein 15 (RBM15), a member of the m6A writer family, assumes a crucial role in recruiting the methyltransferase complex (MTC) and binding to mRNA. Although the impact of m6A modifications on cancer has garnered widespread attention, RBM15 has been relatively overlooked. This review briefly outlines the structure and operational mechanism, and delineates the unique role of RBM15 in various cancers, shedding light on its molecular basis and providing a groundwork for potential tumor-targeted therapies.

BRASH syndrome is a vicious cycle of hyperkalemia and bradycardia and is an under-recognized life-threatening clinical diagnosis. It is usually initiated by hypovolemia or hyperkalemia. We report here on the case of a 92-year-old man with hypertension and heart failure who presented to the emergency department with weakness following diarrhea. He was on amlodipine, benazepril, metoprolol, furosemide and spironolactone. The patient’s blood pressure was 88/53 mmHg and the serum creatinine was 241 μmol/L. Within 2 h, the patient’s heart rate decreased from 58 beats per minute to 26 beats per minute, and serum potassium levels gradually increased from 6.07 mmol/L to 7.3 mmol/L. The electrocardiogram showed a junctional escape rhythm with accidental sinus capture. The diagnosis of BRASH syndrome was made based on clinical symptoms, a biochemical profile and the results of an electrocardiogram. The patient was rapidly stabilized with the administration of intravenous calcium gluconate, dextrose and insulin, 5% sodium bicarbonate, 0.9% sodium chloride, furosemide, and oral zirconium cyclosilicate. Sinus rhythm at a heart rate of 75 bpm was detected 5 h later, along with normal serum potassium levels. After 2 weeks, kidney function returned to normal. Clinicians should be alert to patients with hyperkalemia and maintain a high index of suspicion for BRASH syndrome. Timely diagnosis and comprehensive intervention are critical for better outcomes in managing patients with BRASH.

Abstract Disrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation.

BackgroundIn recent epochs, the field of critical medicine has experienced significant advancements due to the integration of artificial intelligence (AI). Specifically, AI robots have evolved from theoretical concepts to being actively implemented in clinical trials and applications. The intensive care unit (ICU), known for its reliance on a vast amount of medical information, presents a promising avenue for the deployment of robotic AI, anticipated to bring substantial improvements to patient care. ObjectiveThis review aims to comprehensively summarize the current state of AI robots in the field of critical care by searching for previous studies, developments, and applications of AI robots related to ICU wards. In addition, it seeks to address the ethical challenges arising from their use, including concerns related to safety, patient privacy, responsibility delineation, and cost-benefit analysis. MethodsFollowing the scoping review framework proposed by Arksey and O’Malley and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a scoping review to delineate the breadth of research in this field of AI robots in ICU and reported the findings. The literature search was carried out on May 1, 2023, across 3 databases: PubMed, Embase, and the IEEE Xplore Digital Library. Eligible publications were initially screened based on their titles and abstracts. Publications that passed the preliminary screening underwent a comprehensive review. Various research characteristics were extracted, summarized, and analyzed from the final publications. ResultsOf the 5908 publications screened, 77 (1.3%) underwent a full review. These studies collectively spanned 21 ICU robotics projects, encompassing their system development and testing, clinical trials, and approval processes. Upon an expert-reviewed classification framework, these were categorized into 5 main types: therapeutic assistance robots, nursing assistance robots, rehabilitation assistance robots, telepresence robots, and logistics and disinfection robots. Most of these are already widely deployed and commercialized in ICUs, although a select few remain under testing. All robotic systems and tools are engineered to deliver more personalized, convenient, and intelligent medical services to patients in the ICU, concurrently aiming to reduce the substantial workload on ICU medical staff and promote therapeutic and care procedures. This review further explored the prevailing challenges, particularly focusing on ethical and safety concerns, proposing viable solutions or methodologies, and illustrating the prospective capabilities and potential of AI-driven robotic technologies in the ICU environment. Ultimately, we foresee a pivotal role for robots in a future scenario of a fully automated continuum from admission to discharge within the ICU. ConclusionsThis review highlights the potential of AI robots to transform ICU care by improving patient treatment, support, and rehabilitation processes. However, it also recognizes the ethical complexities and operational challenges that come with their implementation, offering possible solutions for future development and optimization.

Sepsis is a clinical syndrome caused by uncontrollable immune dysregulation triggered by pathogen infection, characterized by high incidence, mortality rates, and disease burden. Current treatments primarily focus on symptomatic relief, lacking specific therapeutic interventions. The core mechanism of sepsis is believed to be an imbalance in the host’s immune response, characterized by early excessive inflammation followed by late immune suppression, triggered by pathogen invasion. This suggests that we can develop immunotherapeutic treatment strategies by targeting and modulating the components and immunological functions of the host’s innate and adaptive immune systems. Therefore, this paper reviews the mechanisms of immune dysregulation in sepsis and, based on this foundation, discusses the current state of immunotherapy applications in sepsis animal models and clinical trials.

Gypenosides (Gyp) are bioactive components of Gynostemma pentaphyllum that have a variety of pharmacological properties. Extracts of G. pentaphyllum have been found to be effective in the reduction of blood sugar and lipids and prevention of atherosclerosis. Here, the functions of Gyp and the mechanisms underlying their effects on atherosclerosis were investigated. Mice were allocated to three groups, namely, the control (C57BL/6), atherosclerosis model (ApoE−/− mice with high-fat diet), and Gyp-treated groups. Differentially expressed mRNAs, miRNAs, circRNA, and differential metabolites among the groups were analyzed. The results showed that “Fatty acid metabolism”, “Fatty acid elongation”, “Cytokine-cytokine receptor interaction”, and “PI3K-Akt signaling pathway”, amongst others, were involved in treatment process. Differentially expressed genes, including Fabp1, Apoe, FADS1, ADH1, SYNPO2, and Lmod1were also identified. Mmu-miR-30a and mmu-miR-30e showed reduced expression in atherosclerosis models but were increased following Gyp treatment, suggesting involvement in the effects of Gyp. In addition, chr5:150604177-150608440 were found to interact with mmu-miR-30a and mmu-miR-30e to regulate their abundance. In terms of metabolomics, Gyp may regulate biological processes involving PGD2 and PGJ2, potentially alleviating atherosclerosis. In conclusion, Gyp appeared to have complex effects on atherosclerosis, most of which were positive. These results support the use of Gyp in the treatment of atherosclerosis.

Cholangiocarcinoma is an aggressive and heterogeneous malignancy originating from the bile duct epithelium. It is associated with poor prognosis and high mortality. The global incidence of cholangiocarcinoma is rising, and there is an urgent need for effective early diagnosis and treatment strategies to reduce the burden of this devastating tumor. Small extracellular vesicles, including exosomes and microparticles, are nanoscale vesicles formed by membranes that are released both normally and pathologically from cells, mediating the intercellular transfer of substances and information. Recent studies have demonstrated the involvement of small extracellular vesicles in numerous biological processes, as well as the proliferation, invasion, and metastasis of tumor cells. The present review summarizes the tumorigenic roles of small extracellular vesicles in the cholangiocarcinoma microenvironment. Owing to their unique composition, accessibility, and stability in biological fluids, small extracellular vesicles have emerged as ideal biomarkers for use in liquid biopsies for diagnosing and outcome prediction of cholangiocarcinoma. Specific tissue tropism, theoretical biocompatibility, low clearance, and strong biological barrier penetration of small extracellular vesicles make them suitable drug carriers for cancer therapy. Furthermore, the potential value of small extracellular vesicle-based therapies for cholangiocarcinoma is also reviewed.

Background Given the rapid advancement in technology, the Internet has grown to play a significant role in the field of healthcare. Individuals can now access a profusion of easily available materials for self-management of their health. The purpose of this review is to describe Web/App-based interventions that are primarily or secondarily designed to improve mental health literacy (MHL) and to investigate the effectiveness of online interventions for improving mental health. Materials and Method A scoping review was conducted by searching five databases: PsycINFO, EMBASE, PubMed, CINAHL, and Web of Science. The search was limited to peer-reviewed journals published in English between 2000 and 2022. Studies focusing on enhancements of MHL or its constituent components were included. Results Twenty-four studies met the inclusion criteria. The interventions primarily targeted patients or individuals exhibiting symptoms of mental disorders, with a higher representation of female participants. All the interventions yielded positive outcomes. The included studies were categorized according to three themes: knowledge, attitude, and self-care skills. Although numerous studies have focused on knowledge improvement, research on interventions targeting self-care skills is scarce. Furthermore, existing literature on knowledge enhancement is limited in terms of the coverage of risk factors. Conclusion This review indicates gaps in web/app interventions including limited evidence on risk factors, inconsistent help-seeking awareness, and inadequate self-care skills training. Further research is critically needed to address these deficiencies and promote comprehensive MHL.

In recent years, the installed capacity of photovoltaic solar energy has been increasing year by year. The existing power prediction methods are difficult to achieve reliable power generation prediction for PV equipment that has just been put into service. This poses great difficulties for power system management and dispatching. Therefore, establishing a reliable PV power prediction model for this situation is important for the rapid integration of new-built PV installations into the power system for energy management and dispatching. In this paper, an ultra-short-term PV power prediction method based on coupled information analysis and a dendritic network is proposed. First, an improved Hampel filter is proposed to improve the accuracy of anomaly data processing by analyzing the information between strongly coupled variables. In addition, a dendritic network modeling method is introduced for PV generation prediction. Compared to other solutions, this prediction approach relies on very little historical data to achieve reliable predictions and also features a simple model structure and high generalization. Forty different sets of tests were conducted according to different weather conditions and data conditions. The experimental results show that the proposed method can achieve higher prediction performance and stability compared with the benchmark model.

Abstract Psychosocial and behavioral interventions have been shown to significantly reduce depressive and anxiety symptoms in different populations. Recent evidence suggests that the mental health of the general population has deteriorated significantly since the start of Coronavirus Disease 2019 (COVID-19) pandemic. We conducted a systematic review and meta-analysis of studies on the therapeutic effects of psychosocial and behavioral interventions on depression and anxiety during the COVID-19 pandemic. We systematically searched six electronic databases between December 2019 and February 2022 including PubMed, PsycINFO, Scopus, Web of Science, CNKI, and Wanfang Data. We included randomized clinical trials of psychosocial and behavioral interventions in individuals with depressive or anxiety symptoms during the COVID-19 outbreak compared to various control conditions. A total of 35 eligible studies with 5457 participants were included. The meta-analysis results showed that psychosocial and behavioral interventions had statistically significant moderate effects on depression [SMD = − 0.73, 95% CI (− 1.01, − 0.45), I 2 = 90%] and large effects on anxiety [SMD = − 0.90, 95% CI (− 1.19, − 0.60), I 2 = 92%], especially in the general population and COVID-19 survivors. Exercise and cognitive behavioral therapy were found to be the most effective treatments with moderate-to-large effect size for depression and anxiety during the outbreak of COVID-19. We also found the internet-based approach could also achieve almost equally significant effects on depression and anxiety compared with face-to-face traditional approach. Our findings suggest that cognitive behavioral therapy and physical exercise intervention are significantly effective for depression and anxiety related to the COVID-19 pandemic regardless of the delivery modes, and gender differences should be taken into consideration for better implementation of interventions in clinical and community practice.

Abstract The search for topological superconductivity (TSC) is currently an exciting pursuit, since non-trivial topological superconducting phases could host exotic Majorana modes. However, the difficulty in fabricating proximity-induced TSC heterostructures, the sensitivity to disorder and stringent topological restrictions of intrinsic TSC place serious limitations and formidable challenges on the materials and related applications. Here, we report a new type of intrinsic TSC, namely intrinsic surface topological superconductivity (IS-TSC) and demonstrate it in layered AuSn4 with T c of 2.4 K. Different in-plane and out-of-plane upper critical fields reflect a two-dimensional (2D) character of superconductivity. The two-fold symmetric angular dependences of both magneto-transport and the zero-bias conductance peak (ZBCP) in point-contact spectroscopy (PCS) in the superconducting regime indicate an unconventional pairing symmetry of AuSn4. The superconducting gap and surface multi-bands with Rashba splitting at the Fermi level (E F ), in conjunction with first-principle calculations, strongly suggest that 2D unconventional SC in AuSn4 originates from the mixture of p-wave surface and s-wave bulk contributions, which leads to a two-fold symmetric superconductivity. Our results provide an exciting paradigm to realize TSC via Rashba effect on surface superconducting bands in layered materials.

Abstract Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is characterized by a violent cytokine storm-driven inflammation and is associated with a predisposition to severe disease. The treatment strategy for HTG-AP consists mainly of conventional symptomatic and lipid-lowering treatments. For early-stage HTG-AP, blood purification (BP) can rapidly and effectively reduce serum triglyceride and inflammatory cytokine levels, block the development of systemic inflammatory response syndrome, and improve patient outcomes. Currently, the primary modalities for BP in patients with HTG-AP include plasma exchange, hemoperfusion, and hemofiltration. When using BP to treat patients with HTG-AP, a comprehensive analysis incorporating the elevated lipid levels and severity of the patient’s condition contributes to the selection of different treatment modes. Moreover, the timing of the treatment is also imperative. Early intervention is associated with a better prognosis for patients with HTG-AP requiring lipid-lowering treatment.

Abstract Background Trimethylamine-N-oxide (TMAO), an intestinal microbiota-derived choline metabolite, has been found to be associated with ischemic stroke (IS) in more and more studies. However, the causal role of TMAO on IS occurrence remains perplexing. Methods We comprehensively screened the related clinical studies on PubMed, Web of Science, and Embase. Case-control and cohort studies that reported the TMAO levels of both IS patients and healthy controls were included, and the risk of bias was assessed according to the criteria by the Centre for Evidence-Based Medicine in Oxford, UK. A meta-analysis of the retrieved publications was performed with a random-effect model to analyze the connection between TMAO levels and IS events. Besides, a Mendelian randomization (MR) analysis was performed to study the causal effect of TMAO on IS, with pooled data of TMAO and IS obtained from genome-wide association studies (GWAS). The following methods were used: MR-Egger, weighted median, inverse-variance weighted, simple mode, and weighted mode. The study has been registered in INPLASY (Registration number: INPLASY2023100027). Results Eight cohort or case-control studies covering 2444 cases and 1707 controls were identified. The pooled data indicated that the IS patients tended to have higher TMAO levels compared with the controls (mean difference: 1.97 μM; 95% confidence interval [CI]: 0.87, 3.07; P = 0.0005), while distinctive heterogeneity (I 2 = 96%, P 0.05) in the Mendelian randomization analysis of this study. Conclusion We confirmed that IS patients tend to have higher TMAO levels than healthy individuals, while our findings of MR analysis did not support the causal role of TMAO in IS occurrence. Therefore, more studies are required for a better understanding of the relationship between TMAO levels and IS onset.

Abstract Background Most displaced femoral neck fractures can achieve satisfactory anatomical reduction by closed reduction, but there are still some that cannot reset satisfactorily after closed reduction, and open reduction are required. Such fractures that cannot be repositioned successfully by closed reduction are called irreducible displaced femoral neck fractures in this study. The objective of our study was to evaluate the efficacy of direct anterior incision with the Femoral Neck System in the treatment of irreducible displaced femoral fractures. Methods A total of 16 young and middle-aged patients with irreducible displaced femoral neck fractures involving Garden type III and IV were treated using Femoral Neck System fixation by open reduction through Direct Anterior Approach between January 2020 to September 2021. Functional outcomes and postoperative complications were assessed during follow-up. Clinical outcomes were evaluated by the Hip Harris score. The postoperative reduction was evaluated by the Garden Index. Observe postoperative complications. Results All patients were followed up with a mean follow-up time of 21.1(12–30) months, and according to radiological results, all patients achieved fracture healing, with a mean healing time of 4.25 months. All 16 patients received grade Garden I and II reductions, and there was no significant difference in the anteroposterior Garden reduction index between the first day after surgery (166.13 ± 5.61) and the 12th month after surgery(164.94 ± 4.49) (P>0.05) and no significant difference in lateral Garden index between the first day after surgery(171.06 ± 4.46) and the 12th month after surgery(169.38 ± 3.98) (P

Abstract Background Migrant and left-behind families are vulnerable in health services utilization, but little is known about their disparities in immunization of non-National Immunization Program (NIP) vaccines. This study aims to evaluate the immunization coverage, knowledge, satisfaction, and associated factors of non-NIP vaccines among local and migrant families in the urban areas and non-left-behind and left-behind families in the rural areas of China. Methods A cross-sectional survey was conducted in urban areas of Zhejiang and rural areas of Henan in China. A total of 1648 caregivers of children aged 1–6 years were interviewed face-to-face by a pre-designed online questionnaire, and their families were grouped into four types: local urban, migrant, non-left-behind, and left-behind. Non-NIP vaccines included Hemophilus influenza b (Hib) vaccine, varicella vaccine, rotavirus vaccine, enterovirus 71 vaccine (EV71) and 13-valent pneumonia vaccine (PCV13). Log-binomial regression models were used to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the difference on immunization coverage of children, and knowledge and satisfaction of caregivers among families. The network models were conducted to explore the interplay of immunization coverage, knowledge, and satisfaction. Logistic regression models with odds ratios (ORs) and 95% CIs were used to estimate the associated factors of non-NIP vaccination. Results The immunization coverage of all non-NIP vaccines and knowledge of all items of local urban families was the highest, followed by migrant, non-left-behind and left-behind families. Compared with local urban children, the PRs (95% CIs) for getting all vaccinated were 0.65 (0.52–0.81), 0.29 (0.22–0.37) and 0.14 (0.09–0.21) among migrant children, non-left-behind children and left-behind children, respectively. The coverage-knowledge-satisfaction network model showed the core node was the satisfaction of vaccination schedule. Non-NIP vaccination was associated with characteristics of both children and caregivers, including age of children (> 2 years-OR: 1.69, 95% CI: 1.07–2.68 for local urban children; 2.67, 1.39–5.13 for migrant children; 3.09, 1.23–7.76 for non-left-behind children); and below caregivers’ characteristics: family role (parents: 0.37, 0.14–0.99 for non-left-behind children), age (≤ 35 years: 7.27, 1.39–37.94 for non-left-behind children), sex (female: 0.49, 0.30–0.81 for local urban children; 0.31, 0.15–0.62 for non-left-behind children), physical health (more than average: 1.58, 1.07–2.35 for local urban children) and non-NIP vaccines knowledge (good: 0.45, 0.30–0.68 for local urban children; 7.54, 2.64–21.50 for left-behind children). Conclusions There were immunization disparities in non-NIP vaccines among migrant and left-behind families compared with their local counterparts. Non-NIP vaccination promotion strategies, including education on caregivers, and optimization of the immunization information system, should be delivered particularly among left-behind and migrant families. Graphical Abstract

Abstract Background Nephrectomy, whether in the era of cytokine therapy or targeted therapy, has an important role in the treatment of metastatic renal cell carcinoma. With the advent of immunotherapy, immunotherapy combined with targeted therapy has become the mainstream of systemic therapy, but the role of nephrectomy in metastatic renal cell carcinoma is unclear. In this study, we retrospectively analyzed the impact of nephrectomy on survival in patients with metastatic renal cell carcinoma who received immune-targeted therapy. Methods Patients with metastatic renal cell carcinoma who received immune-targeted therapy at three centers between May 17, 2019 and August 1, 2022 were collected, who were divided into two groups based on whether nephrectomy was performed or not. Survival, response rate and adverse event were compared between the two groups. The primary end point was progression free survival, Subgroup analysis and univariate and multivariable prognostic analyses were also assessed. Results With a median follow-up time of 29.3 months (95% CI 28.5–30.2), 165 patients were recruited and divided into two groups based on whether they underwent nephrectomy or not. There were 68 patients in the non-nephrectomy group, 97 in the nephrectomy group. Compared to patients treated with immune-targeted therapy, patients treated with immune-targeted therapy plus nephrectomy were able to achieve survival benefits, with a median PFS of 10.8 months (95% CI 8.3–13.3) and 14.4 months (95% CI 12.6–16.2), respectively, as well as an HR of 0.476 (95% CI 0.323–0.701, p = 0.0002). The 12-month and 18-month PFS rates were 30.9% versus 60.8% and 7.4% versus 25.8%, respectively. The objective response rate (ORR) was 52.9% and 60.8%, respectively, in the non-nephrectomy and nephrectomy groups (p = 0.313), and the disease control rate (DCR) was 75% and 83.5%, respectively (p = 0.179). The most common adverse events related to treatment were hypothyroidism, immune-related pneumonitis and rash. Multivariate analysis showed that primary tumor nephrectomy prior to immune-targeted therapy, clear cell renal carcinoma and oligo metastasis were independent prognostic factors. Conclusions Nephrectomy may provide PFS benefit with tolerable safety for patients with metastatic renal cell carcinoma who receive immune-targeted therapy. In multivariate analysis, nephrectomy, clear cell carcinoma, and oligo-organ metastasis were found to be favorable independent prognostic factors.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is caused by NOTCH3 mutations affecting the number of cysteines. The pathogenic role of cysteine-sparing NOTCH3 mutations with typical clinical CADASIL syndrome is still debated. This review aimed to characterize NOTCH3 cysteine-sparing mutations in patients with clinical suspicion of CADASIL. Articles on NOTCH3 cysteine-sparing mutations with clinical suspicion of CADASIL were reviewed. Clinical and radiological cerebral phenotypes data were extracted and characterized across regions and compared with phenotypes of typical CADASIL patients. We screened 298 NOTCH3 cysteine-sparing mutation individuals from 20 publications, and mutations in exon 3 were the most frequently reported (21.46%). Gait impairment (76.47%), cognitive impairment (67.47%), and stroke (62.37%) were the three most common clinical phenotypes; the most frequent radiological cerebral phenotypes were lacunes (74.29%) and cerebral microbleeds (72.73%). Compared with CADASIL patients, cognitive impairment and cerebral microbleed frequencies were significantly higher in patients with NOTCH3 cysteine-sparing mutations, while the white matter hyperintensities in anterior temporal polar and external capsule were rarely observed. Compared with Western patients, radiological phenotypes were more common than clinical phenotypes in cysteine-sparing Asian patients. More than half of cysteine-sparing patients had positive granular osmiophilic material deposits. NOTCH3 cysteine-sparing mutations in patients with clinical suspicion of CADASIL mainly manifested with gait and cognitive impairment but rare white matter hyperintensities in anterior temporal pole and external capsule. Further studies are warranted to pay attention to atypical NOTCH3 variants, which could guide specific diagnosis and help unravel underlying mechanisms.

Encryption of images is an important method that can effectively improve the security and privacy of crucial image data. Existing methods generally encrypt an image with a combination of scrambling and encoding operations. Currently, many applications require highly secure results for image encryption. New methods that can achieve improved randomness for both the scrambling and encoding processes in encryption are thus needed to further enhance the security of a cipher image. This paper proposes a new method that can securely encrypt color images. As the first step of the proposed method, a complete bit-level operation is utilized to scramble the binary bits in a color image to a full extent. For the second step, the bits in the scrambled image are processed with a sweeping operation to improve the encryption security. In the final step of encryption, a codebook that varies with evolutionary operations based on several chaotic systems is utilized to encrypt the partially encrypted image obtained in the second step. Experimental results on benchmark color images suggest that this new approach can securely encrypt color images and generate cipher images that remain secure under different types of attacks. The proposed approach is compared with several other state-of-the-art encryption approaches and the results show that it can achieve improved encryption security for cipher images. Experimental results thus suggest that this new approach can possibly be utilized practically in applications where color images need to be encrypted for content protection.

IntroductionThe cost-effectiveness study of syphilis screening in pregnant women has not been synthesized. This study aimed to synthesize the economic evidence on the cost-effectiveness of syphilis screening in pregnant women that might contribute to making recommendations on the future direction of syphilis screening approaches.MethodsWe systematically searched MEDLINE, PubMed, and Web of Science databases for relevant studies published before 19 January 2023 and identified the cost-effectiveness analyses for syphilis screening in pregnant women. The methodological design quality was appraised by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist.ResultsIn total, 17 literature met the eligibility criteria for a full review. Of the 17 studies, four evaluated interventions using different screening methods, seven assessed a combination of syphilis testing and treatment interventions, three focused on repeat screening intervention, and four evaluated the interventions that integrated syphilis and HIV testing. The most cost-effective strategy appeared to be rapid syphilis testing with high treatment rates in pregnant women who were positive.DiscussionThe cost-effectiveness of syphilis screening for pregnancy has been widely demonstrated. It is very essential to improve the compliance with maternal screening and the treatment rates for positive pregnant women while implementing screening.

Summary: Background: Previous observational studies established a positive relationship between snoring and stroke. We aimed to investigate the causal effect of snoring on stroke. Methods: Based on 82,339 unrelated individuals with qualified genotyping data of Asian descent from the China Kadoorie Biobank (CKB), we conducted a Mendelian randomization (MR) analysis of snoring and stroke. Genetic variants identified in the genome-wide association analysis (GWAS) of snoring in CKB and UK Biobank (UKB) were selected for constructing genetic risk scores (GRS). A two-stage method was applied to estimate the associations of the genetically predicted snoring with stroke and its subtypes. Besides, MR analysis among the non-obese group (body mass index, BMI

CD24, also known as heat-stable protein, is a highly glycosylated glycosylphosphatidylinositol junction membrane protein. CD24 specifically binds sialic-acid-binding Ig-like lectin 10 (Siglec10) on macrophages and serves as a “don’t eat me” signal, thus blocking the phagocytosis of tumor cells by macrophages and triggering tumor immune escape. Blocking the CD24-Siglec10 axis to reprogram the tumor immune microenvironment is a current research hotspot in cancer immunotherapy. Targeting the CD24-Siglec10 axis has received widespread attention, because of the high expression of CD24 on a variety of tumor cells and absence of blood toxicity. Targeting the CD24-Siglec10 axis as a cancer immunotherapy has shown favorable results and progress in preclinical studies. In this review, we summarize the discovery and functions of the CD24-Siglec10 axis, and review the roles and effects of this axis as a novel immune checkpoint in cancer immunotherapy. We also highlight recent advances in nanoparticle-mediated treatments targeting the CD24-Siglec10 axis for enhancing cancer immunotherapy.

Abstract Self‐assembled materials with complex nanoscale and mesoscale architecture attract considerable attention in energy and sustainability technologies. Their high performance can be attributed to high surface area, quantum effects, and hierarchical organization. Delineation of these contributions is, however, difficult because complex materials display stochastic structural patterns combining both order and disorder, which is difficult to be consistently reproduced yet being important for materials' functionality. Their compositional variability make systematic studies even harder. Here, a model system of FeSe2 “hedgehog” particles (HPs) was selected to gain insight into the mechanisms of charge storage n complex nanostructured materials common for batteries and supercapacitors. Specifically, HPs represent self‐assembled biomimetic nanomaterials with a medium level of complexity; they display an organizational pattern of spiky colloids with considerable disorder yet non‐random; this patternt is consistently reproduced from particle to particle. . It was found that HPs can accommodate ≈70× greater charge density than spheroidal nano‐ and microparticles. Besides expanded surface area, the enhanced charge storage capacity was enabled by improved hole transport and reversible atomic conformations of FeSe2 layers in the blade‐like spikes associated with the rotatory motion of the Se atoms around Fe center. The dispersibility of HPs also enables their easy integration into energy storage devices. HPs quadruple stored electrochemical energy and double the storage modulus of structural supercapacitors.

Summary: Central nervous sequelae are often reported in recovered patients with COVID-19. It is not clear whether recovered COVID-19 patients have glymphatic impairment and clinical correlation. In this study, we demonstrated that mild COVID-19 patients experienced asymmetric bilateral glymphatic function decline after four months of recovery, and the decrease in glymphatic function was more obvious in older recovered patients. Our results further showed that recovered patients with right-sided glymphatic dysfunction experienced a greater proportion of cognitive decline (MoCA score

Abstract Previous studies on the relationship between dietary minerals and preeclampsia (PE) have given inconsistent results. The aim of this study was to further clarify the relationship between dietary minerals intake and PE in Chinese pregnant women. In this study, 440 pairs of hospital–based preeclamptic and healthy women were matched 1:1. Dietary intake was obtained through a 78–item semi–quantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were plotted to evaluate the dose–response relationship between dietary minerals intake and PE. This study found significant inverse associations for dietary intake of calcium, magnesium, phosphorus, iron, copper, manganese and zinc and the risk of PE in both univariate and multivariate models (all P- trend

Abstract Introduction Clear aligner therapy has become increasingly popular in recent years, although it has encountered several difficulties in premolar extraction treatment. These difficulties include anterior dentition, lingual tipping and extrusion. The design of the present clinical scheme usually set a tiny space between the anterior teeth before retraction in order to obtain an ideal outcome. The objective of our research was to analyze the effect of the existing spaces during retraction. Methods Models including maxillary dentition without first premolars, maxilla, periodontal ligaments, gingiva, or aligners were constructed and imported to an ANSYS workbench. Five groups of models were created: without spaces and with 0.25, 0.50, 0.75 and 1.00 mm spaces between the anterior dentition. A 0.20 mm retraction step was applied to all the groups. Results As the spaces between the anterior dentition increased, the bowing effect of the aligner caused by the passive forces decreased gradually. Accordingly, the degree of extrusion of the anterior dentition was alleviated significantly, while sagittal movement was reduced. However, the overall movement tended to be a bodily displacement rather than tipping. Meanwhile, maximum Von Mises stress of the periodontal ligaments (PDLs) was markedly decreased. Conclusion These analyses indicate that spaces between the anterior dentition during anterior retraction are beneficial for decreasing the tendency for extrusion of the anterior dentition and require provision of anchorage. Appropriate spaces can be designed to lest the lingual tipping and extrusion effect of the anterior teeth while simultaneously reducing the maximum stresses on PDLs.

Abstract Retinal pathological neovascularization involves endothelial cells, pericytes, photoreceptor cells, ganglion cells, and glial cells, whose roles remain unclear. Using the Scissor algorithm, we found that microglia are associated with formation of fibrovascular membranes and can promote pathological neovascularization. GO and KEGG results showed that PI3K-AKT pathway activation in retinal microglia was associated with pathological neovascularization, and PIK3IP1 was associated with retinal microglia activation. Then we used PCR, Western blot and Elisa techniques to confirm that the expression of VEGFA, FGF2, HGFα and MMP9 was increased in microglia after Lipopolysaccharide (LPS) induction. We also used cell flow cytometry and OIR models to verify the role of PI3K-AKT pathway and PIK3IP1 in microglia. Targeting of PIK3IP1 regulated the activation of the PI3K-AKT pathway in microglia, microglia function activation, and pro-angiogenic effects. These findings reveal the role of M1-type microglia in pathological neovascularization and suggests that targeting the PI3K-AKT pathway in microglia may be a new strategy for treating retinal pathological neovascularization.