Tauroursodeoxycholic acid targets HSP90 to promote protein homeostasis and extends healthy lifespan.

As the elderly population expands, the pursuit of therapeutics to reduce morbidity and extend lifespan has become increasingly crucial. As an FDA-approved drug for chronic cholestatic liver diseases, tauroursodeoxycholic acid (TUDCA), a natural bile acid, offers additional health benefits beyond liver protection. Here, we show that TUDCA extends the lifespan and healthspan of C. elegans. Importantly, oral supplementation of TUDCA improves fitness in old mice, including clinically relevant phenotypes, exercise capacity and cognitive function. Consistently, TUDCA treatment drives broad transcriptional changes correlated with anti-aging characteristics. Mechanistically, we discover that TUDCA targets the chaperone HSP90 to promote its protein refolding activity. This collaboration further alleviates aging-induced endoplasmic reticulum (ER) stress and facilitates protein homeostasis, thus offering resistance to aging. In summary, our findings uncover new molecular links between an endogenous metabolite and protein homeostasis, and propose a novel anti-aging strategy that could improve both lifespan and healthspan.

Nursing Staff's Perspectives of Care Robots for Assisted Living Facilities: Systematic Literature Review.

BACKGROUND: Care robots have been proposed in response to nursing shortages in assisted living facilities (ALFs) and the growing population of older adults. While the use of care robots may improve the general health and well-being of older adults, their introduction changes the work of nursing staff fundamentally, and it has implications for the entire health care system. In developing such technology, it is important to include end users, but so far, the nursing staff's perspectives have largely been ignored. OBJECTIVE: This study aims to examine the literature on nursing staff's attitudes, needs, and preferences related to the use of care robots in ALFs, in order to discover gaps in the literature and guide future research. METHODS: This review follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 protocol. On May 12, 2023, we searched PubMed, CINAHL Plus with Full Text, PsycINFO, the IEEE Xplore Digital Library, and the ACM Digital Library using predetermined search terms. Included publications, written in English, focused on the predevelopment phase, in which information was gathered on nursing staff's attitudes, needs, and preferences regarding care robots for ALFs. Publications were excluded if they did not provide peer-reviewed empirical data. The studies' findings were summarized, coded, and analyzed into major themes using thematic analysis and narrative synthesis. Their quality was assessed using McGill University's Mixed Methods Appraisal Tool and the Joanna Briggs Institute's critical appraisal tools. RESULTS: The final sample included 15 studies. Most of the studies (n=11, 73%) were rated as good quality; however, there was a general lack of reporting on important methodological decisions and sample characteristics. Nursing staff desired care robots that could assist with physically demanding tasks and reduce their workload but had mixed feelings on whether robots could or should assist with social tasks. In addition, nursing staff are concerned about the ethics of care robots, as well as about their safety, accessibility, and operability. The nursing staff's culture, qualification, and role in the facility may influence their perspectives of care robots. The studies lacked theory-driven designs and large sample sizes. Eight (53%) studies mentioned using a participatory design approach, but a lack of established criteria for what constitutes participatory design leads to varying degrees of methodological quality. CONCLUSIONS: There was consensus among nursing staff that care robots should serve as nursing assistants to reduce workload. Whether robots could or should assist with social tasks remains a question. Further research is needed to mitigate nursing staff's concerns and understand the socioecological factors that influence their perspectives of care robots and their adoption in ALFs. In addition, theory-driven and large sample size study designs are necessary, as well as work to develop clear criteria for related participatory design research.

Inhibition of transient receptor potential vanilloid 3 channels by antimalarial hydroxychloroquine alleviates TRPV3-dependent dermatitis.

Transient receptor potential vanilloid 3 channel (TRPV3) is closely associated with skin inflammation, but there is a lack of effective and specific inhibitors for clinical use. In this study, we identified antimalarial hydroxychloroquine (HCQ) as a selective TRPV3 inhibitor following the prediction by network pharmacology data analysis. In whole-cell patch-clamp recordings, HCQ inhibited the current of the TRPV3 channel, with an IC50 of 51.69 ± 4.78 µM. At the single-channel level, HCQ reduced the open probability of TRPV3 and decreased single-channel conductance. Molecular docking and site-directed mutagenesis confirmed that residues in the pore domain were critical for the activity of HCQ. In vivo, HCQ effectively reduced carvacrol-induced epidermal thickening, erythema, and desquamation. Additionally, the serum immunoglobulin E and inflammatory factors such as tumor necrosis factor-α and interleukin-6 were markedly decreased in the dorsal skin tissues in the HCQ treatment group, as compared to the model group. Our results suggested the antimalarial HCQ may represent a potential alleviator for treating skin inflammation by inhibiting TRPV3 channels.

Investigating MATN3 and ASPN as novel drivers of gastric cancer progression via EMT pathways.

Gastric cancer (GC) is a leading cause of cancer-related deaths globally, necessitating the identification of novel therapeutic targets. This study investigates the roles of MATN3 and ASPN in GC progression via the epithelial-mesenchymal transition (EMT) pathway. Analysis of the Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD) dataset revealed that both MATN3 and ASPN are significantly upregulated in GC tissues and correlate with poor patient survival. Protein-protein interaction and co-expression analyses confirmed a direct interaction between MATN3 and ASPN, suggesting their synergistic role in EMT activation. Functional assays demonstrated that MATN3 promotes GC cell proliferation, migration, and invasion, while its knockdown inhibits these malignant behaviors and induces apoptosis. ASPN overexpression further amplified these oncogenic effects. In vivo, studies in a mouse model corroborated that co-overexpression of MATN3 and ASPN enhances tumor growth and metastasis. These findings highlight the MATN3-ASPN axis as a potential therapeutic target in GC, offering new insights into the molecular mechanisms driving GC progression.

Abnormal erythrocyte-related parameters in children with Pb, Cr, Cu and Zn exposure.

The link between exposure to a particular heavy metal or metalloid and the development of anemia is well established. However, the association between combined exposure to multiple heavy metal(loid)s and anemia in children is still lacking in evidence. In this study, a total of 266 children aged 3 to 7 were recruited from Guiyu, China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure blood heavy metal(loid) concentrations. Blood cell count, hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), hematocrit (HCT), and red blood cell distribution width (RDW) were measured by an automated hematology analyzer. Erythrocyte-related parameters were negatively correlated with the Cu and Cu/Zn ratios and positively correlated with Cr, Ni, Zn, and Se by Spearman correlation analysis. Only blood Cu level was negatively correlated with HGB [ß = -2.74, (95% Cl: -4.49, -0.995)], MCH [ß = -0.505, (95% Cl: -0.785, -0.226)], MCV [ß = -1.024, (95% Cl: -1.767, -0.281)], and MCHC [ß = -2.137, (95% Cl: -3.54, -0.734)] by multiple linear regression analysis. The Bayesian Kernel Machine Regression (BKMR) model analysis indicated a negative correlation between the combined exposure to Cu, Zn, Pb, and Cr and MCH and MCV. The single-factor analysis showed a considerable statistical difference only with Cu on MCV, MCH, and HGB. Furthermore, the interaction analysis highlighted the interdependent effects of Cu and Zn, Pb and Zn, and Cr and Zn on MCH and MCV levels. Additionally, the oxidation and/or antioxidation reactions may play a significant role in the development of metal(loid)-induced anemia risk. It is crucial to investigate the effects of co-exposure to multiple heavy metal(loid) elements on anemia, especially the interrelationships and mechanisms among them.

N-level complex helical structure modeling method.

This paper primarily explores the modeling method of n-level complex helical structures with coal mining machine cables as the research object. The paper first elaborately introduces the modeling method of n-level helix curves based on parametric equations and coordinate transformations, and compensates for the n-level helix curves with corrected pitch, which can obtain more accurate n-level helix curves and improve the accuracy of n-level helix curves modeling. Subsequently, based on this high-precision n-level helix curves modeling method, the paper elaborates on the method of solving pitch and twisting radius of multi-layer helical structure. Calculation scripts were written based on the above methods, which can be used to batch calculate the twisting radius and pitch of each layer structure in multi-layer structures when satisfying the conditions of in-layer tangency, inter-layer tangency, and extrusion deformation, and retain the actual results through logical judgment. Then, based on the above two methods, the paper developed a modeling method for braided structures based on piecewise functions containing fifth-order polynomials, which can effectively avoid the problem of insufficiently dense arrangement of braided lines and easy interference in traditional methods. Finally, a set of modeling tools was developed using C# and Python in Grasshopper to implement the modeling algorithm. Taking the MCPT-1.9/3.3 3120 + 170 + 4 * 10 coal mining machine cable as an example. The cable was modeled using both the method proposed in this paper and the traditional method. Comparative data shows that the method proposed in this paper can reduce errors by 3.31E6 times in the second-level and above helical structures. In addition this paper compares the standard line length, measured line length, and the line length established by the proposed model, showing that the relative errors are both less than 0.1941%. This paper provides a new, systematic, high-precision, and full-process cable modeling method, in which all parameters except the process parameters are accurately solved by equations. It lays a theoretical foundation for the high-precision simulation and intelligent sensing cables, which is of great significance for improving the safety, stability, and efficient development of the coal mining industry. The research results of the paper can not only be applied to the modeling of coal mining machine cables but also can be extended to the modeling of other complex multi-layer helical structures.

Association between acetaminophen administration and outcomes in critically ill patients with gout and hypertension.

Background: Acetaminophen is a commonly used medication, yet its recommendation for patients with comorbid conditions of gout and hypertension is contradictory, and the impact of its usage on clinical outcomes in real-world practical settings remains uncertain. The aim of this study was to investigate the association between acetaminophen administration and clinical outcomes in critically ill patients with gout and hypertension, utilizing real-world data. Methods: A retrospective cohort study was conducted based on the MIMIC-IV (Medical Information Mart in Intensive Care-IV) database. Adult critically ill patients with gout and hypertension were included in the analysis. The exposure was acetaminophen use during ICU stay. The primary outcome was in-hospital mortality. The secondary endpoints were frequent hospitalization, 30-day, and 60-day all-cause mortality, and incidence of hypertensive emergencies. Propensity score matching (PSM) was conducted at a 1:1 ratio. Multivariable analyses were used to adjust for confounders. Results: The pre-matched and propensity score-matched cohorts included 2448 and 1012 patients, respectively. In the PSM analysis, in-hospital mortality was 9.7% (49/506) in the acetaminophen use group and 12.1% (61/506) in the no use group. Acetaminophen use was associated with a decrease in-hospital mortality (hazard ratio [HR], 0.62; 95% CI, 0.41-0.92; P = 0.018). In terms of secondary endpoints, after PSM, there was no statistically significant difference for both 30-day and 60-day all-cause mortality reductions in the acetaminophen use group, and HRs were 0.78 (95% CI 0.55-1.11; P = 0.175), and 0.75 (95% CI 0.55-1.02; P = 0.069), respectively. According to the analysis of dosage and treatment group, the use of APAP within the dosage range of 2-4 g and within 3-5 days of treatment significantly reduced the mortality rate of the entire cohort and PSM cohort, with statistical differences. Subgroup analysis demonstrated that lower in-hospital mortality was consistent across different baselines (age, gender, BMI, liver disease, and renal disease), with no interactions in all subgroups (interaction p-values >0.05), thereby affirming the robustness and reliability of the findings. Conclusion: Acetaminophen use was associated with lower in-hospital mortality in critically ill patients with gout and hypertension. Prospective studies are needed to verify this finding.

[Relationship Between the Expression of Human Matricellular Protein 3 and the Pathological Features, Drug Resistance, and Prognosis of Gastric Cancer Based on Immunohistochemical Method]. / 人母系蛋白3å‚ä¸Žèƒƒç™Œç»†èƒžæ¶æ€§è¡Œä¸ºä¸”ä¸Žæ‚£è€ ä¸è‰¯é¢„åŽç›¸å ³.

Objective: To observe the relationship between the expression of human matricellular protein 3 (MATN3) and the pathological features, drug resistance, and prognosis of gastric cancer based on immunohistochemical method. Methods: A total of 100 gastric cancer patients treated at the First Affiliated Hospital of Bengbu Medical College from January 2022 to December 2022 were included. MATN3 expression in gastric cancer tissues and paracancerous tissues was assessed by immunohistochemistry. The expression of MATN3 was compared across pathological features. Patients were divided into sensitive and resistant groups based on chemotherapy resistance, and MATN3 expression was compared between these groups. The relationship between MATN3 and recurrence-free survival (RFS) and overall survival (OS) of gastric cancer patients was analyzed using Kaplan-Meier survival curves. Univariate and multifactorial Cox regression analyses were used to analyze the factors affecting the prognosis of gastric cancer patients. Human gastric cancer cells MGC803 were transfected with MATN3. The cells were divided into a high expression group (LV-MATN3 group) and its control group (LV-NC group) and a low expression group (sh-MATN3 group) and its control group (sh-NC group). Cell proliferation was assessed using the CCK8 assay, cell migration and invasion were assessed using the Transwell assay, and MATN3 mRNA expression levels were measured using RT-qPCR. A nude mouse xenograft model was constructed by hypodermic injection of MGC-803 cells transfected with MATN3, and MATN3 mRNA expression levels in tumor tissues were measured using RT-qPCR. Results: Immunohistochemical results showed a significantly higher rate of high MATN3 expression in gastric cancer tissues (64.00%, 64/100) compared to adjacent non-cancerous tissues (31.00%, 31/100) (P<0.05). High MATN3 expression was associated with age ≥60 years old, tumor location in the gastric body, tumor size ≥5 cm, lymph node metastasis (N1-N3), histological differentiation (moderate to high), tumor invasion depth (T3-T4), TNM stage (Ⅲ-Ⅳ), distant organ metastasis, recurrence, and mortality (P<0.05). Among patients with chemotherapy resistance, the high MATN3 expression rate was 79.49% (31/39) in the resistant group compared to 54.10% (33/61) in the sensitive group (P<0.05). Follow-up duration ranged from 11 to 22 months, with a 97.00% follow-up rate and 3 cases lost to follow-up. Kaplan-Meier survival curve analysis showed that patients with high MATN3 expression had significantly lower RFS and OS compared to those with low MATN3 expression (RFS: log-rank=17.291, P<0.001; OS: log-rank=21.719, P<0.001). Multivariate Cox analysis identified high MATN3 expression (hazard ratio [HR]=2.291, 95% confidence interval [CI]: 1.268-5.392), tumor location in the gastric body (HR=2.057, 95% CI: 1.441-5.666), lymph node metastasis (N1-N3) (HR=2.011, 95% CI: 1.010-2.274), tumor invasion depth (T3-T4) (H=2.977, 95% CI: 1.032-7.853), TNM stage Ⅲ-Ⅳ (HR=2.008, 95% CI: 1.049-3.902), and distant organ metastasis (HR=2.505, 95% CI: 1.529-5.000) as independent risk factors affecting RFS and OS (P<0.05). Cell and animal experiments demonstrated that compared to the LV-NC group, the LV-MATN3 group exhibited significantly higher cell proliferation, migration, and invasion (P<0.05), as well as increased tumor volume and MATN3 mRNA expression in tumor tissues (P<0.05). Conversely, the sh-MATN3 group showed significantly reduced cell proliferation, migration, and invasion, along with decreased tumor volume and MATN3 mRNA levels compared to the sh-NC group (P<0.05). Conclusion: MATN3 is highly expressed in gastric cancer tissues and is associated with various pathological features, drug resistance and poor prognosis. MATN3 holds potential as a diagnostic marker for poor prognosis and may play a role in the malignant behaviors of gastric cancer cells, including proliferation, migration, and invasion.

A diet-wide Mendelian randomization analysis: causal effects of dietary habits on type 2 diabetes.

Background: Traditional clinical studies have indicated a link between certain food intakes and type 2 diabetes (T2D), but the causal relationships between different dietary habits and T2D remain unknown. Using Mendelian randomization (MR) approaches, we investigated the potential causal association between dietary habits and T2D risk. Methods: We collected publicly available genome-wide association studies' summary statistics for 18 dietary habits from the UK Biobank and T2D data from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium. We applied the inverse variance weighted (IVW) method, supplemented with the MR-Egger method, weighted median method (WMM), simple method, weighted mode, MR-Egger regression, and the MR pleiotropy residual sum and outlier test to determine whether a particular diet was causal for T2D. Results: Reliable and robust MR estimates demonstrated that poultry intake has a causal effect on a higher risk of T2D (IVW: OR 6.30, 95% CI 3.573-11.11, p = 2.02e - 10; WMM: OR 5.479, 95% CI 0.2758-10.88, p = 1.19e - 06). Conversely, dried fruit intake (IVW: OR 0.380, 95% CI 0.237-0.608, p = 5.57e - 05; WMM: OR 0.450, 95% CI 0.321-0.630, p = 3.33e - 06) and cereal intake (IVW: OR 0.455, 95% CI 0.317-0.653, p = 1.924e - 05; WMM: OR 0.513, 95% CI 0.379-0.694, p = 1.514e - 05) were causally associated with T2D as protective factors. Sensitivity analyses confirmed the reliability and robustness of these findings. Discussion: Our study established the causal effects of poultry intake, dried fruit intake, and cereal intake on T2D, identifying poultry intake as a risk factor and the other two as protective factors. Further research into potential mechanisms is required to validate these novel findings.

Nicotinamide Suppresses Hyperactivation of Dendritic Cells to Control Autoimmune Disease through PARP Dependent Signaling.

Dendritic cells (DCs) are crucial in initiating and shaping both innate and adaptive immune responses. Clinical studies and experimental models have highlighted their significant involvement in various autoimmune diseases, positioning them as promising therapeutic targets. Nicotinamide (NAM), a form of vitamin B3, with its anti-inflammatory properties, has been suggested, while the involvement of NAM in DCs regulation remains elusive. Here, through analyzing publicly available databases, we observe substantial alterations in NAM levels and NAM metabolic pathways during DCs activation. Furthermore, we discover that NAM, but not Nicotinamide Mononucleotide (NMN), significantly inhibits DCs over-activation in vitro and in vivo. The suppression of DCs hyperactivation effectively alleviates symptoms of psoriasis. Mechanistically, NAM impairs DCs activation through a Poly (ADP-ribose) polymerases (PARPs)-NF-κB dependent manner. Notably, phosphoribosyl transferase (NAMPT) and PARPs are significantly upregulated in lipopolysaccharide (LPS)-stimulated DCs and psoriasis patients; elevated NAMPT and PARPs expression in psoriasis patients correlates with higher psoriasis area and severity index (PASI) scores. In summary, our findings underscore the pivotal role of NAM in modulating DCs functions and autoimmune disorders. Targeting the NAMPT-PARP axis emerges as a promising therapeutic approach for DC-related diseases.

Can the postload-fasting glucose gap be used to determine risk of developing diabetes in chinese adults: A prospective cohort study.

OBJECTIVE: To evaluate the relationship between fasting plasma glucose (FPG) and 2-hour postload plasma glucose (2hPG) measured during an oral glucose tolerance test, and the risk of developing diabetes in Chinese adults. METHODS: We followed 3,094 participants without diabetes, categorizing them based on their oral glucose tolerance test (OGTT) results into low post load (2hPG ≤ FPG) and high post load (2hPG > FPG) at baseline. We monitored the incidence of diabetes, incidence of prediabetes, disease progression from prediabetes to diabetes and disease reversal from prediabetes to normal glucose tolerance (NGT) over an average of 3.2 years of follow-up. After the Schoenfeld residual test, Cox's time-varying covariate (Cox-TVC) models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) to compare the different clinical events between low and high post load groups. RESULTS: In the cohort study, of the 3,094 participants, 702 (22.7 %) had low post load (2hPG ≤ FPG, mean postload-fasting gap: -0.8 ± 0.7 mmol/L) and 2,392 (77.3 %) had high post load (2hPG > FPG, mean postload-fasting gap: 1.8 ± 1.2 mmol/L). Over 3.2 ± 0.2 years of follow-up, 282 (9.1 %) developed diabetes. In the low post load group, the incidence rates per 1,000 person-years were: diabetes was 7.9, prediabetes was 70.0, disease progression from prediabetes to diabetes was 23.4 and disease reversal to NGT was 327.2. For the high post load group, incidence rates for diabetes was 13.9, prediabetes was 124.3, disease progression was 59.5 and disease reversal was 238.6 per 1,000 person-years. Participants with high post load showed higher incidence rates of diabetes, prediabetes, and progression from prediabetes to diabetes compared to those with low post load. HRs were significantly higher for incident diabetes and prediabetes, and disease progression from prediabetes to diabetes, whereas disease reversal was lower. CONCLUSION: The risk of developing prediabetes/diabetes after 3.2 years of follow-up was higher in the participants with high post load. It suggested that postload-fasting gap may be a simple tool to predict the risk of developing prediabetes, diabetes or reversal to NGT.

A Simple Prognostic Scoring System for Hepatocellular Carcinoma Treated with DEB-TACE.

Objective: To develop a simple and effective prognostic scoring system to predict the efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC). Methods: Data were retrospectively collected from 230 patients with HCC who received DEB-TACE treatment at six medical centers between January 2019 and December 2022. We developed a predictive score based on independent risk factors for overall survival (OS), validated the model using a validation cohort, and compared its prognostic accuracy with commonly used HCC staging systems. Results: The number of tumors, albumin-bilirubin levels, alpha-fetoprotein levels, and portal vein thrombus grade were identified as independent factors influencing OS. Based on these factors, we established the DEB-TACE treatment of HCC (DTH) scoring system. The DTH score correlated well with OS, which decreased as the DTH score increased. According to the DTH score, patients were categorized into three risk groups: low-risk (DTH-A, 0-4 points), medium-risk (DTH-B, 5-6 points), and high-risk (DTH-A, 7 points). The OS of each risk group was 18.73±0.62 months, 12.73±0.10 months, and 6.93±0.19 months, respectively (p<0.001). The external cohort validation confirmed the accuracy of the DTH score, demonstrating superior predictive performance compared to other commonly used HCC scoring systems. Conclusion: The DTH-HCC scoring system effectively predicts the outcomes of HCC patients undergoing DEB-TACE as initial treatment. This model can aid in the initial planning and decision-making process for DEB-TACE treatment in HCC patients.

Case report: Pyrotinib in the treatment of advanced scrotal EMPD combined with sweat gland carcinoma.

Extramammary Paget disease (EMPD) is a rare cutaneous intraepithelial adenocarcinoma, which is mostly distributed in areas with sweat gland cells and mainly occurs in the anogenital skin of women. The male genital tract involvement is extremely rare and often occurs with other malignant tumors. Paget's disease in the scrotum with sweat gland carcinoma is even rarer. In the first report of scrotal endocrine sweat gland carcinoma associated with Paget disease by Saidi et al. in 1997, no more than 50 cases have been reported in the relevant research worldwide. Early EMPD combined with sweat gland carcinoma is mainly surgical treatment, and there is no standard treatment plan for advanced EMPD with sweat gland carcinoma. Previous article has reported that chemotherapy such as paclitaxel, fluorouracil, platinum, and vinblastine and molecular targeted therapy based on the genetic test results of patients have certain efficacy. Here, we report a 79-year-old male case diagnosed with human epidermal growth factor receptor 2 (HER-2) overexpression, which was effectively controlled by chemotherapy and anti-HER-2 treatment such as pyrotinib.

Extremely large magnetoresistance in twisted intertwined graphene spirals.

Extremely large magnetoresistance (XMR) is highly applicable in spintronic devices such as magnetic sensors, magnetic memory, and hard drives. Typically, XMR is found in Weyl semimetals characterized by perfect electron-hole symmetry or exceptionally high electric conductivity and mobility. Our study explores this phenomenon in a recently developed graphene moiré system, which demonstrates XMR owing to its topological structure and high-quality crystal formation. We investigate the electronic properties of three-dimensional intertwined twisted graphene spirals (TGS), manipulating the screw dislocation axis to achieve a rotation angle of 7.3°. Notably, at 14 T and 2 K, the magnetoresistance of these structures reaches 1.7 × 107%, accompanied by a metal-insulator transition as the temperature increases. This transition becomes noticeable when the magnetic field exceeds a minimal threshold of approximately 0.1 T. These observations suggest the possible existence of complex, correlated states within the partially filled three-dimensional Landau levels of the 3D TGS system. Our findings open up possibilities for achieving XMR by engineering the topological structure of 2D layered moiré systems.

Artificial intelligence in dentistry: A bibliometric analysis from 2000 to 2023.

Background/purpose: Artificial intelligence (AI) is reshaping clinical practice in dentistry. This study aims to provide a comprehensive overview of global trends and research hotspots on the application of AI to dentistry. Materials and methods: Studies on AI in dentistry published between 2000 and 2023 were retrieved from the Web of Science Core Collection. Bibliometric parameters were extracted and bibliometric analysis was conducted using VOSviewer, Pajek, and CiteSpace software. Results: A total of 651 publications were identified, 88.7 % of which were published after 2019. Publications originating from the United States and China accounted for 34.5 % of the total. The Charité Medical University of Berlin was the institution with the highest number of publications, and Schwendicke and Krois were the most active authors in the field. The Journal of Dentistry had the highest citation count. The focus of AI in dentistry primarily centered on the analysis of imaging data and the dental diseases most frequently associated with AI were periodontitis, bone fractures, and dental caries. The dental AI applications most frequently discussed since 2019 included neural networks, medical devices, clinical decision support systems, head and neck cancer, support vector machine, geometric deep learning, and precision medicine. Conclusion: Research on AI in dentistry is experiencing explosive growth. The prevailing research emphasis and anticipated future development involve the establishment of medical devices and clinical decision support systems based on innovative AI algorithms to advance precision dentistry. This study provides dentists with valuable insights into this field.

Quantitative proteomics insights into Chlamydomonas reinhardtii thermal tolerance enhancement by a mutualistic interaction with Sinorhizobium meliloti.

Interactions between photosynthetic microalgae and bacteria impact the physiology of both partners, which influence the fitness and ecological trajectories of each partner in an environmental context-dependent manner. Thermal tolerance of Chlamydomonas reinhardtii can be enhanced through a mutualistic interaction with vitamin B12 (cobalamin)-producing Sinorhizobium meliloti. Here, we used label-free quantitative proteomics to reveal the metabolic networks altered by the interaction under normal and high temperatures. We created a scenario where the growth of Sinorhizobium requires carbon provided by Chlamydomonas for growth in co-cultures, and survival of Chlamydomonas under high temperatures relies on cobalamin and possibly other metabolites produced by Sinorhizobium. Differential abundance analysis identified proteins produced by each partner in co-cultures compared to mono-cultures at each temperature. Proteins involved in cobalamin production by Sinorhizobium increased in the presence of Chlamydomonas under elevated temperatures, whereas in Chlamydomonas, there was an increase in cobalamin-dependent methionine synthase and certain proteins associated with methylation reactions. Co-cultivation and heat stress strongly modulated the central metabolism of both partners as well as various transporters that could facilitate nutrient cross-utilization. Co-cultivation modulated expression of various components of two- or one-component signal transduction systems, transcriptional activators/regulators, or sigma factors, suggesting complex regulatory networks modulate the interaction in a temperature-dependent manner. Notably, heat and general stress-response and antioxidant proteins were upregulated in co-cultures, suggesting that the interaction is inherently stressful to each partner despite the benefits of mutualism. Our results shed insight into the metabolic tradeoffs required for mutualism and how metabolic networks are modulated by elevated temperature. IMPORTANCE: Photosynthetic microalgae are key primary producers in aquatic ecosystems, playing an important role in the global carbon cycle. Nearly every alga lives in association with a diverse community of microorganisms that influence each other and their metabolic activities or survival. One chemical produced by bacteria that influence algae is vitamin B12, an enzyme cofactor used for a variety of metabolic functions. The alga Chlamydomonas reinhardtii benefits from vitamin B12 produced by Sinorhizobium meliloti by producing the amino acid methionine under high temperatures which are required for Chlamydomonas thermotolerance. Yet, our understanding of this interaction under normal and stressful temperatures is poor. Here, we used quantitative proteomics to identify differentially expressed proteins to reveal metabolic adjustments made by Chlamydomonas and Sinorhizobium that could facilitate this mutualism. These findings will enhance our understanding of how photosynthetic algae and their associated microbiomes will respond as global temperatures increase.

Effectiveness and safety of sequential transarterial chemoembolization and microwave ablation for subphrenic hepatocellular carcinoma: A comprehensive evaluation.

BACKGROUND: Subphrenic carcinoma has been identified as a significant risk factor for the thermal ablation of intrahepatic tumors, resulting in a high rate of residual tumor recurrence. Some studies have proposed that combination treatment with transarterial chemoembolization (TACE) followed by radiofrequency ablation is both feasible and safe for tumors in the subphrenic region. However, research specifically examining the therapeutic outcomes of combination therapy using TACE and microwave ablation (TACE-MWA) in subphrenic tumors is lacking. AIM: To evaluate the efficacy and safety of TACE-MWA in patients with subphrenic hepatocellular carcinoma (HCC). METHODS: Between December 2017 and December 2021, 49 patients diagnosed with HCC ≤ 6 cm, who received TACE-MWA, were included in this retrospective cohort study. These patients were classified into subphrenic and non-subphrenic groups based on the distance between the diaphragm and the tumor margin. The rates of local tumor progression (LTP), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Complications were evaluated by using a grading system developed by the Society of Interventional Radiology. RESULTS: After a median follow-up time of 38 mo, there were no significant differences in LTP between the subphrenic and non-subphrenic groups (27.3% and 22.2% at 5 years, respectively; P = 0.66), PFS (55.5% at 5 years in both groups; P = 0.91), and OS (85.0% and 90.9% in the subphrenic and non-subphrenic groups at 5 years; P = 0.57). However, a significantly higher rate of LTP was observed in subphrenic HCC > 3 cm compared to those ≤ 3 cm (P = 0.085). The dosage of iodized oil [hazard ratio (HR): 1.52; 95% confidence interval (CI): 1.11-2.08; P = 0.009] and multiple tumors (HR: 13.22; 95%CI: 1.62-107.51; P = 0.016) were independent prognostic factors for LTP. There were no significant differences in complication rates between the two groups (P = 0.549). CONCLUSION: Combined TACE and MWA was practical and safe for managing subphrenic HCC. The efficacy and safety levels did not vary significantly when tumors outside the subphrenic region were treated.

Expression profile of long noncoding RNAs and comprehensive analysis of lncRNA-cisTF-DGE regulation in condyloma acuminatum.

OBJECTIVE: To identify differentially expressed long noncoding RNAs (lncRNAs) in condyloma acuminatum (CA) and to explore their probable regulatory mechanisms by establishing coexpression networks. METHODS: High-throughput RNA sequencing was performed to assess genome-wide lncRNA expression in CA and paired adjacent mucosal tissue. The expression of candidate lncRNAs and their target genes in larger CA specimens was validated using real-time quantitative reverse transcriptase polymerase chain reaction (RT‒qPCR). Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for the functional enrichment analysis of these candidate lncRNAs and differential mRNAs. The coexpressed mRNAs of the candidate lncRNAs, calculated by Pearson's correlation coefficient, were also analysed using GO and KEGG analysis. In addition, the interactions among differentially expressed lncRNAs (DElncRNAs)-cis-regulatory transcription factors (cisTFs)-differentially expressed genes (DEGs) were analysed and their network was constructed. RESULTS: A total of 546 lncRNAs and 2553 mRNAs were found to be differentially expressed in CA compared to the paired control. Functional enrichment analysis revealed that the DEGs coexpressed with DElncRNAs were enriched in the terms of cell adhesion and keratinocyte differentiation, and the pathways of ECM-receptor interaction, local adhesion, PI3K/AKT and TGF-ß signaling. We further constructed the network among DElncRNAs-cisTFs-DEGs and found that these 95 DEGs were mainly enriched in GO terms of epithelial development, regulation of transcription or gene expression. Furthermore, the expression of 3 pairs of DElncRNAs and cisTFs, EVX1-AS and HOXA13, HOXA11-AS and EVX1, and DLX6-AS and DLX5, was validated with a larger number of specimens using RT‒qPCR. CONCLUSION: CA has a specific lncRNA profile, and the differentially expressed lncRNAs play regulatory roles in mRNA expression through cis-acting TFs, which provides insight into their regulatory networks. It will be useful to understand the pathogenesis of CA to provide new directions for the prevention, clinical treatment and efficacy evaluation of CA.