Search

BackgroundOver the last two decades, patient review websites have emerged as an essential online platform for doctor ratings and reviews. Recent studies suggested the significance of such websites as a data source for patients to choose doctors for healthcare providers to learn and improve from patient feedback and to foster a culture of trust and transparency between patients and healthcare providers. However, as compared to other medical specialties, studies of online patient reviews that focus on dentists in the United States remain absent. ObjectiveThis study sought to understand to what extent online patient reviews can provide performance feedbacks that reflect dental care quality and patient experience. MethodsUsing mixed informatics methods incorporating statistics, natural language processing, and domain expert evaluation, we analyzed the online patient reviews of 204,751 dentists extracted from HealthGrades with two specific aims. First, we examined the associations between patient ratings and a variety of dentist characteristics. Second, we identified topics from patient reviews that can be mapped to the national assessment of dental patient experience measured by the Patient Experience Measures from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Dental Plan Survey. ResultsHigher ratings were associated with female dentists (t71881=2.45, P

Considering the significance of lifelong learning in advancing active aging in aging societies, the ability to engage in self-directed learning plays a crucial role for adults. There are many self-directed learning (SDL) tools available that measure the SDL abilities of nursing students and healthcare professionals. However, fewer SDL tools specifically designed for middle-aged and older adults have been developed. The purpose of this research was to examine and confirm the factor structure and the internal consistency of the SRSSDL-adult scale, specifically for middle-aged and older adult learners enrolled in senior learning centers. A cross-sectional method was adopted. Both Exploratory Factor Analysis and Confirmatory Factor Analysis were conducted to assess the structural validity of the scale. The internal consistency was determined using the Cronbach's Alpha coefficient. The results indicated that the five factors -- learning needs assessment skills, learning planning skills, learning execution skills, self-assessment skills, and interpersonal skills -- showed acceptable levels of reliability. The revised 25-item SRSSDL-adult scale was found to be a valid measure of middle-aged and older adults' self-directed learning abilities in the context of senior education programs. The findings of this study have the potential to be utilized by educational institutions and educators involved in senior education programs.

Abstract This review explores the intricate roles of metal ions—iron, copper, zinc, and selenium—in glioma pathogenesis and immune evasion. Dysregulated metal ion metabolism significantly contributes to glioma progression by inducing oxidative stress, promoting angiogenesis, and modulating immune cell functions. Iron accumulation enhances oxidative DNA damage, copper activates hypoxia-inducible factors to stimulate angiogenesis, zinc influences cell proliferation and apoptosis, and selenium modulates the tumor microenvironment through its antioxidant properties. These metal ions also facilitate immune escape by upregulating immune checkpoints and secreting immunosuppressive cytokines. Targeting metal ion pathways with therapeutic strategies such as chelating agents and metalloproteinase inhibitors, particularly in combination with conventional treatments like chemotherapy and immunotherapy, shows promise in improving treatment efficacy and overcoming resistance. Future research should leverage advanced bioinformatics and integrative methodologies to deepen the understanding of metal ion-immune interactions, ultimately identifying novel biomarkers and therapeutic targets to enhance glioma management and patient outcomes.

Abstract The SARS-CoV-2 Omicron variant sparked the largest wave of infections worldwide. Mainland China eased its strict COVID-19 measures in late 2022 and experienced two nationwide Omicron waves in 2023. Here, we investigated lineage distribution and virus evolution in Guangdong, China, 2022-2023 by comparing 5813 local viral genomes with the datasets from other regions of China and worldwide. Additionally, we conducted three large-scale serological surveys involving 1696 participants to measure their immune response to the BA.5 and XBB.1.9 before and after the corresponding waves. Our findings revealed the Omicron variants, mainly the BA.5.2.48 lineage, causing infections in over 90% of individuals across different age groups within a month. This rapid spread led to the establishment of widespread immunity, limiting the virus’s ability to further adaptive mutation and dissemination. While similar immune responses to BA.5 were observed across all age groups after the initial wave, children aged 3 to 11 developed a stronger cross immune response to the XBB.1.9 strain, possibly explaining their lower infection rates in the following XBB.1 wave. Reinfection with Omicron XBB.1 variant triggered a more potent neutralizing immune response among older adults. These findings highlight the impact of age-specific immune responses on viral spread in potential future waves.

Abstract The progression of Parkinson’s disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20–89 years; 33% female) and 885 controls (age: 19–84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen’s d effect sizes reached d = −1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder.

Abstract Background There are several surgical options for osteonecrosis of the lunate, and confirming the effectiveness of various surgical methods remains challenging. Here, we present a case of stage IIIB osteonecrosis of the lunate repaired with a free medial femoral condyle osteocutaneous flap. Case presentation A 43-year-old male construction worker was admitted to our hospital due to right wrist pain, impaired mobility, and pain aggravated by activity for 10 months. The patient was diagnosed with stage IIIB osteonecrosis of the lunate based on the orthopantomogram and magnetic resonance imaging of the right wrist. Considering the patient’s medical history, physical examination, auxiliary examination, and wishes, reconstruction was performed using a free medial femoral condyle osteocutaneous flap. After the flap survived completely, the K-wires were removed one month after the operation, the external brace was removed two months after the operation, and functional wrist rehabilitation was initiated. After six months of follow-up, the wrist swelling and pain resolved, and the reconstructed lunate bone was viable. Additionally, the last follow-up was conducted in the sixth month after surgery; the affected hand grip strength improved from about 70% (28 kg) to 80% (32 kg) compared with the healthy side (40 kg); the visual analog scale score decreased from 6.5 points before the operation to 1 point; and the MAYO score increased from 60 points before the operation to 85 points. Conclusions The success of this case reinforces the potential of the free medial femoral condyle osteocutaneous flap as a new treatment option for stage IIIB osteonecrosis of the lunate and further expands the existing treatment options. Using a free medial femoral condyle osteocutaneous flap to reconstruct the lunate and restore the carpal anatomy may.

Abstract Parking difficulties have become a social issue that people have to solve. Automated parking system is practicable for quick par operations without a driver which can also greatly reduces the probability of parking accidents. The paper proposes a Lyapunov-based nonlinear model predictive controller embedding an instructable solution which is generated by the modified rear-wheel feedback method (RF-LNMPC) in order to improve the overall path tracking accuracy in parking conditions. Firstly, A discrete-time RF-LNMPC considering the position and attitude of the parking vehicle is proposed to increase the success rate of automated parking effectively. Secondly, the RF-LNMPC problem with a multi-objective cost function is solved by the Interior-Point Optimization, of which the iterative initial values are described as the instructable solutions calculated by combining modified rear-wheel feedback to improve the performance of local optimal solution. Thirdly, the details on the computation of the terminal constraint and terminal cost for the linear time-varying case is presented. The closed-loop stability is verified via Lyapunov techniques by considering the terminal constraint and terminal cost theoretically. Finally, the proposed RF-LNMPC is implemented on a self-driving Lincoln MKZ platform and the experiment results have shown improved performance in parallel and vertical parking conditions. The Monte Carlo analysis also demonstrates good stability and repeatability of the proposed method which can be applied in practical use in the near future.

Abstract High thermal conductivity aluminium-based silicon carbide (Al/SiC) composites were successfully fabricated through post-oxidization of reaction-bonded silicon carbide preforms (RS preforms), utilizing vacuum pressure infiltration technology. The study investigated the regulation of interfacial reactions in conventional sintering and reaction sintering. Conventional sintering introduced a large amount of SiO2, which negatively impacted the thermal conductivity of the Al/SiC composite, but the reaction sintering not. The proposed post-oxidization treatment of RS preforms effectively removed residual carbon from the SiC particle surfaces, thereby forestalling the formation of Al4C3. Furthermore, the post-oxidization treatment effectively formed lightweight SiO2 deposits onto the surface of SiC particles, improving Al-SiC interfacial wettability and reducing thermal resistance, thereby enhancing composite thermal conductivity. Notably, the thermal conductivity of the post-oxidized sample exhibited an increase of 6.5% compared to the untreated sample. The study also evaluated the impact of particle size distribution on volume fraction and thermal properties. The optimized Al/SiC composites yielded thermal conductivity, coefficient of thermal expansion, bending strength, and Young’s modulus values of 237.3 W/m K, 8.5 × 10−6/°C, 325 MPa, and 75.9 GPa, respectively.

Abstract Physical layer key generation (PLKG) is a technique of information-theoretic security to tackle the problem of key distribution between resource-constrained legitimate users and is a promising candidate for the one time pad (OTP) technique. However, in quasi-static, the key rate is greatly limited due to low entropy. Reconfigurable intelligent surface (RIS) is introduced to adaptively reconfigure the radio environment. However, how to allocate time slots in the OTP to counter the increasingly powerful adversary model is an urgent problem to be solved. In this paper, we propose a very powerful adversary model and give an attack strategy called eavesdropping channel search, which allows Eve to use its search and eavesdropping capabilities to maximize the probability of successful attacks. Meanwhile, we propose a time slot allocation algorithm in the OTP to ensure the security of the key. Simulations validate that our proposed attack strategy is more powerful than any existing adversary model and our proposed time slot allocation algorithm does not have any security loss.

Abstract Challenges in direct catalytic oxidation of biomass-derived aldehyde and alcohol into acid with high activity and selectivity hinder the widespread biomass application. Herein, we demonstrate that a Pd/Ni(OH)2 catalyst with abundant Ni2+-O-Pd interfaces allows electrooxidation of 5-hydroxymethylfurfural to 2, 5-furandicarboxylic acid with a selectivity near 100 % and 2, 5-furandicarboxylic acid yield of 97.3% at 0.6 volts (versus a reversible hydrogen electrode) in 1 M KOH electrolyte under ambient conditions. The rate-determining step of the intermediate oxidation of 5-hydroxymethyl-2-furancarboxylic acid is promoted by the increased OH species and low C–H activation energy barrier at Ni2+-O-Pd interfaces. Further, the Ni2+-O-Pd interfaces prevent the agglomeration of Pd nanoparticles during the reaction, greatly improving the stability of the catalyst. In this work, Pd/Ni(OH)2 catalyst can achieve 100% 5-hydroxymethylfurfural conversion and >90% 2, 5-furandicarboxylic acid selectivity in a flow-cell and work stably over 200 h under a fixed cell voltage of 0.85 V.

Abstract Background The energy/protein imbalance in a low-protein diet induces lipid metabolism disorders in late-phase laying hens. Reducing energy levels in the low-protein diet to adjust the energy-to-protein ratio may improve fat deposition, but this also decreases the laying performance of hens. This study investigated the mechanism by which different energy levels in the low-protein diet influences liver lipid metabolism in late-phase laying hens through the enterohepatic axis to guide feed optimization and nutrition strategies. A total of 288 laying hens were randomly allocated to the normal-energy and normal-protein diet group (positive control: CK) or 1 of 3 groups: low-energy and low-protein diet (LL), normal-energy and low-protein diet (NL), and high-energy and low-protein diet (HL) groups. The energy-to-protein ratios of the CK, LL, NL, and HL diets were 0.67, 0.74, 0.77, and 0.80, respectively. Results Compared with the CK group, egg quality deteriorated with increasing energy intake in late-phase laying hens fed low-protein diet. Hens fed LL, NL, and HL diets had significantly higher triglyceride, total cholesterol, acetyl-CoA carboxylase, and fatty acid synthase levels, but significantly lower hepatic lipase levels compared with the CK group. Liver transcriptome sequencing revealed that genes involved in fatty acid beta-oxidation (ACOX1, HADHA, EHHADH, and ACAA1) were downregulated, whereas genes related to fatty acid synthesis (SCD, FASN, and ACACA) were upregulated in LL group compared with the CK group. Comparison of the cecal microbiome showed that in hens fed an LL diet, Lactobacillus and Desulfovibrio were enriched, whereas riboflavin metabolism was suppressed. Cecal metabolites that were most significantly affected by the LL diet included several vitamins, such as riboflavin (vitamin B2), pantethine (vitamin B5 derivative), pyridoxine (vitamin B6), and 4-pyridoxic acid. Conclusion A lipid metabolism disorder due to deficiencies of vitamin B2 and pantethine originating from the metabolism of the cecal microbiome may be the underlying reason for fat accumulation in the liver of late-phase laying hens fed an LL diet. Based on the present study, we propose that targeting vitamin B2 and pantethine (vitamin B5 derivative) might be an effective strategy for improving lipid metabolism in late-phase laying hens fed a low-protein diet.

To explore the moisture variation law of high oleic peanuts during hot air drying, hot air drying characteristics of various high oleic peanuts under different hot air temperatures (35, 40, 45, 50 ℃) and hot air velocities (0.5, 0.8, 1.1 m/s) were studied in this paper, and their drying processes were analyzed by Weibull distribution function. The results showed that the drying process of high oleic peanuts mainly reduced the rate of drying. Increasing hot air temperature and hot air velocity led to a higher effective moisture diffusion coefficient for high oleic peanuts. In turn, accelerates drying rate and shortens drying time. Among all the peanuts, 'Shengyou 3' peanut had the fastest water diffusion rate and lowest activation energy, and the Weibull distribution function provided the most suitable fit for 'Shengyou 3'. The scale parameter α decreased as hot air temperature and hot air velocity increase. Hot air temperature had a highly significant effect on α (P

Complex formation structures lead to significant differences in the failure mechanisms of hobs. WC-reinforced medium entropy composite coatings exhibit excellent comprehensive properties. However, the wear mechanism of coatings in different formation structures is still unclear. In this study, FeNiCr-WCx (x = 0, 40, 50, 60 wt%) composite coatings were prepared on the surface of H13 steel using laser cladding technology. The friction and wear mechanism of FeNiCr-WC composite coatings under different friction pair conditions was discussed. The results show that FeNiCr-WC composite coatings mainly consist of reinforced phase, lamellar eutectic structure and solid solution phase. As the WC content increases, the content of M6C and carbide phases in these coatings increases. The average microhardness of 40WC, 50WC and 60WC coatings is 3.28 times, 3.61 times and 4.20 times that of H13 steel, respectively. The wear rates of 40WC, 50WC and 60WC coatings are respectively about 0.25, 0.10 and 0.06 times that of FeNiCr coating under Al2O3 friction pair conditions. Three-body wear and oxidation wear mainly occurred on the surface of FeNiCr-WC composite coatings. The wear rates of 40WC, 50WC and 60WC coatings are respectively about 0.34, 0.35 and 0.16 times that of FeNiCr coating under Si3N4 friction pair conditions. Glaze layers with high Si content were formed on the surface of 50WC and 60WC coatings. The glaze layer is prone to cracking and peeling, resulting in increased wear rates for both coatings. As the hardness of the coating increases, the GCr15 friction pair undergoes severe abrasive wear.

Abstract Suitable biomaterials with seed cells have promising potential to repair bone defects. However, bone marrow mesenchymal stem cells (BMSCs), one of the most common seed cells used in tissue engineering, cannot differentiate efficiently and accurately into functional osteoblasts. In view of this, a new tissue engineering technique combined with BMSCs and scaffolds is a major task for bone defect repair. Lentiviruses interfering with miR‐136‐5p or Smurf1 expression were transfected into BMSCs. The effects of miR‐136‐5p or Smurf1 on the osteogenic differentiation (OD) of BMSCs were evaluated by measuring alkaline phosphatase activity and calcium deposition. Then, the targeting relationship between miR‐136‐5p and Smurf1 was verified by bioinformatics website analysis and dual luciferase reporter assay. Then, a rabbit femoral condyle bone defect model was established. miR‐136‐5p/BMSCs/β‐TCP scaffold was implanted into the defect, and the repair of the bone defect was detected by Micro‐CT and HE staining. Elevating miR‐136‐5p‐3p or suppressing Smurf1 could stimulate OD of BMSCs. miR‐136‐5p negatively regulated Smurf1 expression. Overexpressing Smurf1 reduced the promoting effect of miR‐136‐5p on the OD of BMSCs. miR‐136‐5p/BMSCs/β‐TCP could strengthen bone density in the defected area and accelerate bone repair. SmurF1‐targeting miR‐136‐5p‐modified BMSCs combined with 3D‐printed β‐TCP scaffolds can strengthen osteogenic activity and alleviate bone defects.

Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases. However, unidirectional targeting gene therapy is always desired at the tissue interface. In this study, inspired by the principle that like charges repulse each other, a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers, thus realizing unidirectional gene therapy at the tendon-paratenon interface. Under the charge repulsion of positively charged layer, more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue, which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation, but also avoided adverse effects on the fragile endogenous healing of tendon itself. In summary, this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.

Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration (IVDD). Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc. This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1 (TGF-β1) (T-NNPs) onto the surface of methacrylic acid gelatin anhydride microspheres (GM) via amide bonds. The nanoparticle-microsphere complex (GM@T-NNPs) sustained the long-term release of T-NNPs with excellent cell-like functions, effectively bound to pro-inflammatory cytokines, and improved the release kinetics of TGF-β1, maintaining a 36 day-acting release. GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro, downregulated the expression of inflammatory factors and matrix metalloproteinase, and upregulated the expression of collagen-II and aggrecan. GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model. The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.

Exonic circular RNAs (ecircRNAs) in animal cells are generated by backsplicing, and the biogenesis of ecircRNAs is regulated by an array of RNA binding proteins (RBPs). HNRNPD is a heterogeneous nuclear ribonucleoprotein family member with both cytoplasmic and nuclear roles, and whether HNRNPD regulates the biogenesis of circRNAs remains unknown. In this study, we examine the role of HNRNPD in the biogenesis of ecircRNAs. The levels of ecircRNAs are primarily increased upon depletion of HNRNPD. HNRNPD preferentially binds to motifs enriched with A and U nucleotides, and the flanking introns of ecircRNAs tend to have more numbers and higher intensity of HNRNPD binding sites. The levels of mRNAs are generally not significantly altered in HNRNPD knockout cells. For a small set of genes, the circRNA:mRNA ratio is substantially affected, and the mRNA levels of some of these genes demonstrate a significant decrease in HNRNPD knockout cells. CDK1 is identified as a key gene modulated by HNRNPD in the context of circRNA biogenesis. HNRNPD suppresses the biogenesis of circCDK1 and favours the generation of CDK1 mRNA, and the CDK1 protein is a critical regulator of the cell cycle and apoptosis. HNRNPD can participate in cellular physiology, including the cell cycle and apoptosis, and plays roles in clear cell renal cell carcinoma (ccRCC) by modulating circRNA biogenesis and the mRNA levels of key genes, such as CDK1.

Background Henoch-Schonlein purpura is a vascular inflammatory illness that develops in childhood and in some children involves the kidneys, clinically known as Henoch-Schonlein purpura nephritis. Different studies have suggested different interventions, and there is a wide variation in the outcome indicators used for the intervention approaches. Objective To investigate and analyze the current status of clinical research outcome indicators for Henoch-Schonlein purpura nephritis in China, so as to provide a reference basis for the establishment of a core set of outcome indicators in this field. Methods CNKI, CBM, VIP, Wanfang Data, PubMed, Cochrane Library, Embase and Web of Science were systematically searched to collect publicly available Henoch-Schonlein purpura nephritis studies from January 2010 to June 2021. The Chinese databases were searched using the search strategy of title or keywords combined with subject terms, and the English databases were searched using subject terms combined with free words. Two investigators independently screened the literature and extracted information according to the inclusion and exclusion criteria, processed and analyzed the data on outcome indicators. Results A total of 148 randomized controlled trials of Henoch-Schonlein purpura nephritis were included, and the outcome indicators of Henoch-Schonlein purpura nephritis studies were mainly physical and chemical indicators, with fewer symptomatic indicators. The highest frequency of outcome indicators were clinical efficacy (121 times, 81.76%), adverse reactions (74 times, 50.00%), 24-hour urine protein (68 times, 45.95%), urinary red blood cells (43 times, 29.05%), and recurrence rate (20 times, 13.51%). The division between primary and secondary outcome indicators was clearly distinguished in only two articles. Conclusion There are several indicators for the research outcomes of Henoch-Schonlein purpura nephritis in China, primarily physical and chemical variables, with significant variation. The research focuses on efficacy measures but ignores adverse reactions. As a result, it is necessary to establish a set of outcome indicators for clinical intervention studies on Henoch-Schonlein purpura nephritis in order to provide a reference basis for selecting outcome indicators and guiding clinical decision-making in future similar studies.

Irregular bone defects, characterized by unpredictable size, shape, and depth, pose a major challenge to clinical treatment. Although various bone grafts are available, none can fully meet the repair needs of the defective area. Here, this study fabricates a dough-type hydrogel (DR-Net), in which the first dynamic network is generated by coordination between thiol groups and silver ions, thereby possessing kneadability to adapt to various irregular bone defects. The second rigid covalent network is formed through photocrosslinking, maintaining the osteogenic space under external forces and achieving a better match with the bone regeneration process. In vitro, an irregular alveolar bone defect is established in the fresh porcine mandible, and the dough-type hydrogel exhibits outstanding shape adaptability, perfectly matching the morphology of the bone defect. After photocuring, the storage modulus of the hydrogel increases 8.6 times, from 3.7 kPa (before irradiation) to 32 kPa (after irradiation). Furthermore, this hydrogel enables effective loading of P24 peptide, which potently accelerates bone repair in Sprague–Dawley (SD) rats with critical calvarial defects. Overall, the dough-type hydrogel with kneadability, space-maintaining capability, and osteogenic activity exhibits exceptional potential for clinical translation in treating irregular bone defects.

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson’s disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson’s disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson’s disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore, bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson’s disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson’s disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson’s disease, particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremor-dominant and non-tremor-dominant Parkinson’s disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity, and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson’s disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.

Objective To explore the risk factors for sleep disorders in maintenance hemodialysis （MHD） patients and construct a risk prediction model. Methods A retrospective study was conducted among 198 patients who underwent MHD between January 2018 and December 2022. Based upon whether or not there were complications of sleep disorders, they were assigned into two groups of sleep disorder （n = 134） and non-sleep disorder （n = 64）. Uni/multivariate Logistic regression analyses were performed for identifying the risk factors for sleep disorders in MHD patients. A nomogram model for sleep disorders in MHD patients was constructed with software R. The discrimination and calibration of this model were tested using the receiver operating characteristic （ROC） curve and calibration curve. Internal validation of this model was conducted byBootstrap. Results The total PSQI score was （10.32 ± 1.34）. There were 134 patients with PSQI score ≥7 and the incidence of sleep disorders was 67.68%（134/198）. Uni/multivariate Logistic regression analyses revealed that dialysis duration （OR = 1.573）, skin pruritus （OR = 3.044）, restless leg syndrome （RSL）（OR = 2.722） and serum parathyroid hormone （PTH）（OR = 1.030） were risk factors for sleep disorders in MHD patients （P

Abstract We revisit the masses of heavy quarkonium double-gluon hybrid mesons with exotic quantum numbers J PC = 1−+ and 2+− in the framework of the QCD sum rules. Considering the double-gluon hybrid meson operators in the octet-octet color structure, we have constructed two independent interpolating currents with J PC = 1−+ and five independent currents with J PC = 2+−. For the interpolating currents with antisymmetric glueball operator, there exist non-local divergences in one kind of additional Feynman diagrams of the tri-gluon condensate, which will give important contributions to the sum rule stabilities and mass predictions. We use the diagrammatic renormalization to cancel out such divergences. At the leading order of α s , the two-point correlation functions and spectral densities can be expressed in the analytic form of the generalized hypergeometric functions and Meijer’s G-functions. After performing the numerical analysis, we predict the masses of the 1−+ and 2+− charmonium double-gluon hybrid mesons to be around 6.1 − 7.2 GeV and 6.3 − 6.4 GeV, respectively. For the bottomonium systems, their masses are predicted to be 13.7 − 14.3 GeV and 12.6 − 13.3 GeV for the 1−+ and 2+− channels, respectively. Besides, it is possible to hunt for these charmonium hybrids in the radiative decays of bottomonium mesons in BelleII experiment. Further investigations on these hybrid states in various theoretical and phenomenological methods are also anticipated in the future.

Abstract Quantum heat engines and refrigerators are open quantum systems, whose dynamics can be well understood using a non-Hermitian formalism. A prominent feature of non-Hermiticity is the existence of exceptional points (EPs), which has no counterpart in closed quantum systems. It has been shown in classical systems that dynamical encirclement in the vicinity of an EP, whether the loop includes the EP or not, could lead to chiral mode conversion. Here, we show that this is valid also for quantum systems when dynamical encircling is performed in the vicinity of their Liouvillian EPs (LEPs), which include the effects of quantum jumps and associated noise—an important quantum feature not present in previous works. We demonstrate, using a Paul-trapped ultracold ion, the first chiral quantum heating and refrigeration by dynamically encircling a closed loop in the vicinity of an LEP. We witness the cycling direction to be associated with the chirality and heat release (absorption) of the quantum heat engine (quantum refrigerator). Our experiments have revealed that not only the adiabaticity breakdown but also the Landau–Zener–Stückelberg process play an essential role during dynamic encircling, resulting in chiral thermodynamic cycles. Our observations contribute to further understanding of chiral and topological features in non-Hermitian systems and pave a way to exploring the relation between chirality and quantum thermodynamics.

Abstract Background Autophagy is crucial for controlling the manifestation of tuberculosis. This study intends to discover autophagy-related molecular clusters as biomarkers for discriminating between latent tuberculosis (LTBI) and active tuberculosis (ATB) in children through gene expression profile analysis. Methods The expression of autophagy modulators was examined in pediatric patients with LTBI and ATB utilizing public datasets from the Gene Expression Omnibus (GEO) collection (GSE39939 and GSE39940). Results In a training dataset (GSE39939), patients with LTBI and ATB exhibited the expression of autophagy-related genes connected with their active immune responses. Two molecular clusters associated with autophagy were identified. Compared to Cluster 1, Cluster 2 was distinguished through decreased adaptive cellular immune response and enhanced inflammatory activation, according to single-sample gene set enrichment analysis (ssGSEA). Per the study of gene set variation, Cluster 2’s differentially expressed genes (DEGs) played a role in synthesizing transfer RNA, DNA repair and recombination, and primary immunodeficiency. The peak variation efficiency, root mean square error, and area under the curve (AUC) (AUC = 0.950) were all lowered in random forest models. Finally, a seven-gene-dependent random forest profile was created utilizing the CD247, MAN1C1, FAM84B, HSZFP36, SLC16A10, DTX3, and SIRT4 genes, which performed well against the validation dataset GSE139940 (AUC = 0.888). The nomogram calibration and decision curves performed well in identifying ATB from LTBI. Conclusions In summary, according to the present investigation, autophagy and the immunopathology of TB might be correlated. Furthermore, this investigation established a compelling prediction expression profile for measuring autophagy subtype development risks, which might be employed as possible biomarkers in children to differentiate ATB from LTBI.

Objectives: Eravacycline, a new tetracycline derivative, exhibits broad-spectrum antimicrobial susceptibility. This study aimed to comprehensively investigate in vitro activities of eravacycline, tigecycline, and ertapenem against various Gram-positive, Gram-negative, and anaerobic bacteria. Methods: Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. The following bacterial species were collected: vancomycin-sensitive (VS) Enterococci species, vancomycin-resistant Enterococci species (VRE), Staphylococcus aureus, Streptococcus anginosus, Bacteroides species, Clostridioides difficile, Clostridium innocuum, Clostridium perfringens, Parabacteroides distasonis, and Stenotrophomonas maltophilia. Results: We found that eravacycline exhibited superior in vitro activity compared to tigecycline and ertapenem. Notably, it exhibited the lowest MIC90 for several bacterial species, including VS E. faecalis (0.12 µg/mL), VS E. faecium (0.12 µg/mL), and others. Besides, VRE was susceptible to eravacycline (MIC90:0.12 µg/mL) and tigecycline (MIC90:0.12 µg/mL), but was all resistant to ertapenem (MIC90 > 64 µg/mL). S. aureus was also susceptible to eravacycline (MIC90:0.5 µg/mL) as well as tigecycline (MIC90:1.0 µg/mL). Furthermore, S. anginosus showed higher susceptibility to eravacycline (MIC90:2.0 µg/mL) and tigecycline (MIC90:4.0 µg/mL), but lower to ertapenem (MIC90:32.0 µg/mL). Eravacycline and tigecycline also demonstrated good susceptibility to anaerobes, including Bacteroides species (susceptibility rate: 100%), P. distasonis (100%), C. difficile (94.1‒100%), C. innocuum (94.1‒96.1%), and C. perfringens (88.9‒96.3%). For S. maltophilia, both tigecycline and eravacycline showed an MIC90 of 2 µg/mL. A moderate-to-strong correlation (rho = 0.608–0.804, P < 0.001) was noted between the MIC values of eravacycline and tigecycline against various bacterial species. Conclusions: Our study highlights the potential of eravacycline as an effective treatment option for multidrug-resistant bacterial infections.

Abstract As a facilitator of smart upgrading, digital twin (DT) is emerging as a driving force in prognostics and health management (PHM). Faults can lead to degradation or malfunction of industrial assets. Accordingly, DT-driven PHM studies are conducted to improve reliability and reduce maintenance costs of industrial assets. However, there is a lack of systematic research to analyze and summarize current DT-driven PHM applications and methodologies for industrial assets. Therefore, this paper first analyzes the application of DT in PHM from the application field, aspect, and hierarchy at application layer. The paper next deepens into the core and mechanism of DT in PHM at theory layer. Then enabling technologies and tools for DT modeling and DT system are investigated and summarized at implementation layer. Finally, observations and future research suggestions are presented.

Abstract Background Cerebral cavernous malformations (CCMs) are vascular abnormalities associated with deregulated angiogenesis. Their pathogenesis and optimal treatment remain unclear. This study aims to investigate the molecular signatures of cuproptosis, a newly identified type of cell death, associated with CCMs development. Methods Bulk RNA sequencing (RNA-seq) from 15 CCM and 6 control samples were performed with consensus clustering and clustered to two subtypes based on expression levels of cuproptosis-related genes (CRGs). Differentially expressed genes and immune infiltration between subtypes were then identified. Machine learning algorithms including the least absolute shrinkage and selection operator and random forest were employed to screen for hub genes for CCMs associated with cuproptosis. Furthermore, Pathway enrichment and correlation analysis were used to explore the functions of hub genes and their association with immune phenotypes in CCMs. An external dataset was then employed for validation. Finally, employing the Cellchat algorithm on a single-cell RNA-seq dataset, we explored potential mechanisms underlying the participation of these hub genes in cell-cell communication in CCMs. Results Our study revealed two distinct CCM subtypes with differential pattern of CRG expression and immune infiltration. Three hub genes (BTBD10, PFDN4, and CEMIP) were identified and validated, which may significantly associate with CCM pathogenesis. These genes were found to be significantly upregulated in CCM endothelial cells (ECs) and were validated through immunofluorescence and western blot analysis. Single-cell RNA-seq analysis revealed the cellular co-expression patterns of these hub genes, particularly highlighting the high expression of BTBD10 and PFDN4 in ECs. Additionally, a significant co-localization was also observed between BTBD10 and the pivotal cuproptosis gene FDX1 in Mki67+ tip cells, indicating the crucial role of cuproptosis for angiogenesis in CCMs. The study also explored the cell-cell communication between subcluster of ECs expressing these hub genes and immune cells, particularly M2 macrophages, suggesting a role for these interactions in CCM pathogenesis. Conclusion This study identifies molecular signatures linking cuproptosis to CCMs pathogenesis. Three hub genes—PFDN4, CEMIP, and BTBD10—may influence disease progression by modulating immunity. Further research is needed to understand their precise disease mechanisms and evaluate their potential as biomarkers or therapeutic targets for CCMs.

Abstract Background Chrysanthemum morifolium Ramat, a traditional Chinese medicine, has the effects on liver clearing, vision improving, and anti-inflammation. C. morifolium and probiotics have been individually studied for their beneficial effects on metabolic diseases. However, the underlying molecular mechanisms were not completely elucidated. This study aims to elucidate the potential molecular mechanisms of C. morifolium and probiotics combination (CP) on alleviating nonalcoholic fatty liver disease (NAFLD) and the dysregulation of glucose metabolism in high-fat diet (HFD)-fed mice. Methods The therapeutic effect of CP on metabolism was evaluated by liver histology and serum biochemical analysis, as well as glucose tolerance test. The impact of CP on gut microbiota was analyzed by 16S rRNA sequencing and fecal microbiota transplantation. Hepatic transcriptomic analysis was performed with the key genes and proteins validated by RT-qPCR and western blotting. In addition, whole body Pparα knockout (Pparα −/−) mice were used to confirm the CP-mediated pathway. Results CP supplementation ameliorated metabolic disorders by reducing body weight and hepatic steatosis, and improving glucose intolerance and insulin resistance in HFD fed mice. CP intervention mitigated the HFD-induced gut microbiota dysbiosis, which contributed at least in part, to the beneficial effect of improving glucose metabolism. In addition, hepatic transcriptomic analysis showed that CP modulated the expression of genes associated with lipid metabolism. CP downregulated the mRNA level of lipid droplet-binding proteins, such as Cidea and Cidec in the liver, leading to more substrates for fatty acid oxidation (FAO). Meanwhile, the expression of CPT1α, the rate-limiting enzyme of FAO, was significantly increased upon CP treatment. Mechanistically, though CP didn’t affect the total PPARα level, it promoted the nuclear localization of PPARα, which contributed to the reduced expression of Cidea and Cidec, and increased expression of CPT1α, leading to activated FAO. Moreover, whole body PPARα deficiency abolished the anti-NAFLD effect of CP, suggesting the importance of PPARα in CP-mediated beneficial effect. Conclusion This study revealed the hypoglycemic and hepatoprotective effect of CP by regulating gut microbiota composition and PPARα subcellular localization, highlighting its potential for therapeutic candidate for metabolic disorders.

CircRNAs are a class of single-stranded RNAs characterized by covalently looped structures. Emerging advances have promoted our understanding of circRNA biogenesis, nuclear export, biological functions, and functional mechanisms. Roles of circRNAs in diverse diseases have been increasingly recognized in the past decade, with novel approaches in bioinformatics analysis and new strategies in modulating circRNA levels, which have made circRNAs the hot spot for therapeutic applications. Moreover, due to the intrinsic features of circRNAs such as high stability, conservation, and tissue-/stage-specific expression, circRNAs are believed to be promising prognostic and diagnostic markers for diseases. Aiming cardiovascular disease (CVD), one of the leading causes of mortality worldwide, we briefly summarize the current understanding of circRNAs, provide the recent progress in circRNA functions and functional mechanisms in CVD, and discuss the future perspectives both in circRNA research and therapeutics based on existing knowledge.

Objective To investigate the feasibility of a deep learning model for the fully automatic classification of disc degeneration based on lumbar structures on sagittal T2WI images. Methods The lumbar T2WI image data of 94 patients who underwent lumbar spine MRI examination in the Third Affiliated Hospital of Anhui Medical University from August 2020 to June 2022 were retrospectively selected，and 466 discs were obtained. The lumbar intervertebral disc were manually annotated by 2 radiologists on sagittal T2WI images．The data were randomly divided into train set (n=300)，validation set (n=72)，and test set (n=94). Firstly, a U-Net network was used to train the disc segmentation model. The evaluation indexes of the model included Dice coefficient and IoU score. Then, SpineNet network was used to train the classification model, and the evaluation indexes of the model included accuracy, sensitivity, specificity, F1 score, and ROC curves. Results In the test set, the dice coefficient and IoU values of U-Net model for lumbar disc segmentation were 0.920 and 0.853, respectively. The accuracy, specificity and sensitivity value of SpineNet classification models for lumbar disc degeneration were 0.913, 0.912 and 0.916, respectively. The ROC curve analysis showed that the AUC values for distinguishing mild to moderate, mild to serious, and moderate to serious lumbar disc degeneration were 0.89, 0.95, and 0.90, respectively. Conclusion It is feasible to realize the fully automatic classification of disc degeneration based on deep learning network.