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Abstract Patients with neurogenic rosacea (NR) frequently demonstrate pronounced neurological manifestations, often unresponsive to conventional therapeutic approaches. A molecular-level understanding and diagnosis of this patient cohort could significantly guide clinical interventions. In this study, we amalgamated our sequencing data (n = 46) with a publicly accessible database (n = 38) to perform an unsupervised cluster analysis of the integrated dataset. The eighty-four rosacea patients were partitioned into two distinct clusters. Neurovascular biomarkers were found to be elevated in cluster 1 compared to cluster 2. Pathways in cluster 1 were predominantly involved in neurotransmitter synthesis, transmission, and functionality, whereas cluster 2 pathways were centered on inflammation-related processes. Differential gene expression analysis and WGCNA were employed to delineate the characteristic gene sets of the two clusters. Subsequently, a diagnostic model was constructed from the identified gene sets using linear regression methodologies. The model's C index, comprising genes PNPLA3, CUX2, PLIN2, and HMGCR, achieved a remarkable value of 0.9683, with an area under the curve (AUC) for the training cohort's nomogram of 0.9376. Clinical characteristics from our dataset (n = 46) were assessed by three seasoned dermatologists, forming the NR validation cohort (NR, n = 18; non-neurogenic rosacea, n = 28). Upon application of our model to NR diagnosis, the model's AUC value reached 0.9023. Finally, potential therapeutic candidates for both patient groups were predicted via the Connectivity Map. In summation, this study unveiled two clusters with unique molecular phenotypes within rosacea, leading to the development of a precise diagnostic model instrumental in NR diagnosis.

Abstract Rosacea patients show facial hypersensitivity to stimulus factors (such as heat and capsaicin); however, the underlying mechanism of this hyperresponsiveness remains poorly defined. Here, we show capsaicin stimulation in mice induces exacerbated rosacea-like dermatitis but has no apparent effect on normal skin. Nociceptor ablation substantially reduces the hyperresponsiveness of rosacea-like dermatitis. Subsequently, we find that γδ T cells express Ramp1, the receptor of the neuropeptide CGRP, and are in close contact with these nociceptors in the skin. γδ T cells are significantly increased in rosacea skin lesions and can be further recruited and activated by neuron-secreted CGRP. Rosacea-like dermatitis is reduced in T cell receptor δ-deficient (Tcrd−/−) mice, and the nociceptor-mediated aggravation of rosacea-like dermatitis is also reduced in these mice. In vitro experiments show that CGRP induces IL17A secretion from γδ T cells by regulating inflammation-related and metabolism-related pathways. Finally, rimegepant, a CGRP receptor antagonist, shows efficacy in the treatment of rosacea-like dermatitis. In conclusion, our findings demonstrate a neuron-CGRP-γδT cell axis that contributes to the hyperresponsiveness of rosacea, thereby showing that targeting CGRP is a potentially effective therapeutic strategy for rosacea.

Single-atom catalysts (SACs) exhibit outstanding catalytic activity due to their highly dispersed metal centers. Activating persulfates (PS) with SACs can generate various reactive oxygen species (ROS) to efficiently degrade emerging organic contaminants (EOCs) in aqueous environments, offering unique advantages such as high reaction rates and excellent stability. This technique has been extensively researched and holds enormous potential applications. In this paper, we comprehensively elaborated on the synthesis methods of SACs and their limitations, and factors influencing the catalytic performance of SACs, including metal center characteristics, coordination environment, and types of substrates. We also analyzed practical considerations for application. Subsequently, we discussed the mechanism of SACs activating PS for EOCs degradation, encompassing adsorption processes, radical pathways, and non-radical pathways. Finally, we provide prospects and outline our vision for future research, aiming to guide advancements in applying this technique. HIGHLIGHTS Summarized the synthesis methods of single-atom catalysts and limitations.; Discussed the factors influencing the performance of single-atom catalysts and practical factors.; Elucidated the mechanism of SACs activating PS for EOCs degradation and prospects for the future.;

Abstract In recent years, significant improvement has been made in the management of non‐small cell lung cancer (NSCLC), primarily driven by advances in targeted therapy and immunotherapy. Research on neoadjuvant targeted therapy has also experienced considerable development, primarily directed towards NSCLC harboring epidermal growth factor receptor or anaplastic lymphoma kinase mutations. Nevertheless, there remains a dearth of studies investigating neoadjuvant targeted therapy in the context of BRAF (V‐Raf murine sarcoma viral oncogene homolog B) V600E mutant NSCLC. Herein, we describe the clinical trajectory of a stage IIIA NSCLC patient who underwent a two‐month course of neoadjuvant targeted therapy comprising BRAF and MEK (mitogen‐activated extracellular signal‐regulated kinase) inhibitors prior to surgical intervention, and subsequent postoperative evaluation unveiled a pathological complete response. The case reported here indicates the efficacy and safety of combining BRAF and MEK inhibitors as neoadjuvant targeted therapy in BRAF V600E‐mutant NSCLC and suggests the potential viability of such a therapeutic modality in improving treatment outcomes in this subset of NSCLC.

Abstract Background Fungal periprosthetic joint infection (FPJI) is an infrequent but devastating complication that imposes a heavy burden on patients. At present, a consensus regarding the most optimal surgical option for patients with FPJI, the ideal duration of systemic antifungal treatment, and many other issues has not been reached. Methods A comprehensive literature search was performed on the PubMed and Embase databases. The search criteria employed were as follows: (fungal OR candida OR mycotic) AND periprosthetic joint infection. Initially, the titles and abstracts were screened, and subsequently, studies deemed irrelevant or duplicative were eliminated. Following this, the complete texts of remaining articles were thoroughly examined. According to the inclusion and exclusion criteria, 489 joints in 24 articles were screened out. We further extracted the demographic characteristics (age, gender, body mass index, etc.), clinical presentation, fungal species, presence of bacterial coinfection, surgical methods, systemic and local antifungal therapy, and treatment outcomes. Subgroup data were analyzed according to fungal species and bacterial coinfection. Univariate logistic regression analysis was conducted to ascertain the risk factors associated with the infection recurrence. Results A total of 506 fungi were identified within 489 joints. The most prevalent fungal species were Candida albicans (41.5%). Out of 247 joints (50.5%) presenting with concurrent fungal and bacterial infections. Among the initial surgical interventions, two-stage exchange was the most common (59.1%). The infection recurrence rates of DAIR, resection arthroplasty, two-stage, one-stage, and three-stage exchange were 81.4%, 53.1%, 47.7%, 35.0%, and 30%, respectively. The mean duration of systemic antifungal therapy was 12.8 weeks. The most common drugs used both in intravenous (55.9%) and oral therapy (84.0%) were fluconazole. The proportion of patients who used antifungal drugs after replantation (two-stage and three-stage) was 87.6%. 33.2% of cement spacer or fixed cement contained antifungal drugs, of which amphotericin B was the main choice (82.7%). FPJI caused by candida albicans (OR = 1.717, p = 0.041) and DAIR (OR = 8.433, p = 0.003) were risk factors for infection recurrence. Conclusions Two-stage exchange remains the most commonly used surgical approach. The reliability of one- and three-exchange needs further evaluation due to the small sample size. Antifungal-loaded cement spacers, and direct intra-articular injections of antimycotics after reimplatation should be strongly considered. Medication is not standardized but rather individualized according to microbiology and the status of patients.

Abstract Background Malignant mesothelioma (MM) is an exceedingly rare tumor with poor prognosis due to the limited availability of effective treatment. Immunotherapy has emerged as a novel treatment approach for MM, but less than 40% of the patients benefit from it. Thus, it is necessary to identify accurate and effective biomarkers that can predict the overall survival (OS) and immunotherapy efficacy for MM. Methods DNA sequencing was used to identify the genomic landscape based on the data from 86 Chinese patients. T cell receptor (TCR) sequencing was used to characterize MM TCR repertoires of 28 patients between October 2016 and April 2023. Results Patients with TP53, NF2, or CDKN2A variants at the genomic level, as well as those exhibiting lower Shannon index (

Abstract Background Currently, the differentiation between benign and malignant cystic pulmonary nodules poses a significant challenge for clinicians. The objective of this retrospective study was to construct a predictive model for determining the likelihood of malignancy in patients with cystic pulmonary nodules. Methods The current study involved 129 patients diagnosed with cystic pulmonary nodules between January 2017 and June 2023 at the Neijiang First People’s Hospital. The study gathered the clinical data, preoperative imaging features of chest CT, and postoperative histopathological results for both cohorts. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors, from which a prediction model and nomogram were developed. In addition, The model's performance was assessed through receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Results A cohort of 129 patients presenting with cystic pulmonary nodules, consisting of 92 malignant and 37 benign lesions, was examined. Logistic data analysis identified a cystic airspace with a mural nodule, spiculation, mural morphology, and the number of cystic cavities as significant independent predictors for discriminating between benign and malignant cystic lung nodules. The nomogram prediction model demonstrated a high level of predictive accuracy, as evidenced by an area under the ROC curve (AUC) of 0.874 (95% CI: 0.804–0.944). Furthermore, the calibration curve of the model displayed satisfactory calibration. DCA proved that the prediction model was useful for clinical application. Conclusion In summary, the risk prediction model for benign and malignant cystic pulmonary nodules has the potential to assist clinicians in the diagnosis of such nodules and enhance clinical decision-making processes.

Abstract Background Deciphering the role of plasma proteins in pancreatic cancer (PC) susceptibility can aid in identifying novel targets for diagnosis and treatment. Methods We examined the relationship between genetically determined levels of plasma proteins and PC through a systemic proteome-wide Mendelian randomization (MR) analysis utilizing cis-pQTLs from multiple centers. Rigorous sensitivity analyses, colocalization, reverse MR, replications with varying instrumental variable selections and additional datasets, as well as subsequent meta-analysis, were utilized to confirm the robustness of significant findings. The causative effect of corresponding protein-coding genes’ expression and their expression pattern in single-cell types were then investigated. Enrichment analysis, between-protein interaction and causation, knock-out mice models, and mediation analysis with established PC risk factors were applied to indicate the pathogenetic pathways. These candidate targets were ultimately prioritized upon druggability and potential side effects predicted by a phenome-wide MR. Results Twenty-one PC-related circulating proteins were identified in the exploratory phase with no evidence for horizontal pleiotropy or reverse causation. Of these, 11 were confirmed in a meta-analysis integrating external validations. The causality at a transcription level was repeated for neutrophil elastase, hydroxyacylglutathione hydrolase, lipase member N, protein disulfide-isomerase A5, xyloside xylosyltransferase 1. The carbohydrate sulfotransferase 11 and histo-blood group ABO system transferase exhibited high-support genetic colocalization evidence and were found to affect PC carcinogenesis partially through modulating body mass index and type 2 diabetes, respectively. Approved drugs have been established for eight candidate targets, which could potentially be repurposed for PC therapies. The phenome-wide investigation revealed 12 proteins associated with 51 non-PC traits, and interference on protein disulfide-isomerase A5 and cystatin-D would increase the risk of other malignancies. Conclusions By employing comprehensive methodologies, this study demonstrated a genetic predisposition linking 21 circulating proteins to PC risk. Our findings shed new light on the PC etiology and highlighted potential targets as priorities for future efforts in early diagnosis and therapeutic strategies of PC.

Objective: Through meta-analysis, this study aims to comprehensively evaluate the efficacy of single-plating and double-plating in the treatment of comminuted fractures of the distal femur. Methods: Computer searches of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang digital journals were performed, and the timeframe for the searches was from the establishment of each database to July 2023 for each of the databases. Meta-analysis was performed using RevMan 5.4 software provided by the Cochrane Library, and the review process was registered in the PROSPERO database. Results: A total of ten studies were included for statistical analysis. One randomised controlled study and nine retrospective cohort studies with a total of 563 patients were included. The double-plate group was superior to the single-plate group in terms of knee mobility at 6 months postoperatively, overall postoperative complications, and the rate of healing of knee deformity. However, it increased the operation time and intraoperative bleeding, and the difference between the two groups was statistically significant (P < 0.05). There was no significant difference between the two groups in terms of excellent knee function rate, fracture healing time, plate fracture, postoperative infection, delayed fracture healing, and non-union (P ≥ 0.05). Conclusion: Double plate fixation for comminuted fractures of the distal femur can improve knee mobility at 6 months postoperatively, reduce overall postoperative complications, and decrease the incidence of malunion healing. However, it increases operative time and bleeding. Randomised studies are needed to provide strong evidence in the future.

Abstract Steady-State Microbunching (SSMB) has been proposed as a concept to generate coherent synchrotron radiation at an electron storage ring. SSMB promises to supply kilowatt level average power radiation in the extreme ultraviolet regime, meeting the power level demands for lithography applications that presently cannot be fulfilled by established accelerator technologies. SSMB is under theoretical and experimental study, building on a proof-of-principle (PoP) experiment at the Metrology Light Source which previously showed the viability of the idea. Here we report experimental findings from systematic studies in the ongoing SSMB PoP experiment, where microbunching is generated from an energy modulation imposed by a laser of wavelength 1064 nm. The results confirm the expected dependence of the microbunching process on modulation amplitude and show that the influence of transverse-longitudinal coupling dynamics is as predicted. This confirmation of key parts of the SSMB theory establishes a solid footing for continuing the proof-of-principle efforts towards the goal of constructing a prototype SSMB light source facility.

Abstract Background Further explore the safety and feasibility of Uni-portal video assisted thoracoscopic (UVATS) left upper lobectomy by optimizing the treatment of incisions and blood vessels. Methods We conducted a retrospective analysis of data from 32 patients who underwent UVATS left upper lobectomy and systematic mediastinal lymph node dissection utilizing the Export priority technique between January 2021 and December 2022. We documented perioperative indicators, including surgical time, intraoperative blood loss, the number of lymph nodes dissected, and postoperative pathological staging. Results All surgeries were conducted utilizing the Export priority technique in UVATS. The mean surgical duration was (98.93 ± 14.98) minutes, with an average intraoperative blood loss of (79.53 ± 37.96) ml. The mean count of dissected lymph nodes was (13.96 ± 2.69). The length of hospital Stay averaged (5.62 ± 1.81) days. On the first postoperative day, the thoracic drainage volume was (101.87 ± 49.46) ml. The mean duration of postoperative thoracic tube insertion was (3.1 ± 1.84) days. No occurrences of postoperative hoarseness, pulmonary infection, or complications such as bronchopleural fistula were observed. Conclusion The application of the Export priority technique improves the safety and feasibility of UVATS left upper lobectomy.

This paper introduces a comprehensive and resilient multi-energy system (MES) designed for independent planning and real-time implementation. A robust daily coordinated planning model is proposed, incorporating adjustable optimization with fundamental operational and uncertainty constraints. The model integrates various energy sources and systems, including photovoltaics, wind turbines, combined heat and power (CHP) units, energy storage system (ESS), electric vehicle (EV), electric boilers, and power-to-gas (P2G) facilities, to manage electricity, natural gas, and heat demands. The objective is to minimize MES operational costs while meeting electricity and heat requirements, considering renewable energy uncertainties. It includes the development of a two-stage flexible robust optimization model that accounts for energy equilibrium, capacity constraints, and demand response mechanisms. The model incorporates price-based demand response with both switchable and interruptible loads, enhancing system controllability and flexibility. Additionally, a scenario generation and reduction technique based on the Kantorovich distance is employed to effectively manage forecast errors and uncertainties. A novel modified Slime Mold Algorithm (SMA) is utilized to solve the optimization problem, demonstrating superior convergence and computational efficiency compared to traditional meta-heuristics. The slime mold algorithm is further enhanced with chaos theory, using a sine map to introduce dynamic exploration capabilities. The findings indicate that the proposed multi-energy system model effectively balances electricity, natural gas, and heat loads while accommodating renewable energy fluctuations. The enhanced slime mold algorithm provides optimal solutions swiftly, ensuring reliable and cost-effective multi-energy system operation.

Purpose To assess the value of pretreatment neutrophil-to-lymphocyte ratio (NLR) and systemic immunoinflammatory index (SII) in the prognosis of nasopharyngeal carcinoma (NPC) patients. Methods This retrospective study analyzed a total of 185 NPC patients who visited the clinic from June 2015 to December 2018 and were selected as study subjects. The NLR and SII were calculated based on the collection of demographic information, clinical characteristics, and pre-treatment lymphocyte counts, neutrophil counts, and platelet counts. Predictive efficacy was evaluated using the receiver operating characteristic (ROC) curve, and survival analysis was performed through life table methods and Cox risk-proportional regression. Results Using the X-tile software, significant differences were found in clinical factors among NPC patients based on NLR (>2.91) and SII (>535.47). Age, TNM staging, SII, and NLR were identified as independent prognostic factors in a Cox regression analysis. SII had the highest area under the curve (AUC) for predicting 1-year survival, TNM staging had the highest AUC for predicting 3-year survival, and NLR had the highest AUC for predicting 5-year survival. The combined model showed superior predictive accuracy across all time points. Conclusion NLR and SII, as biomarkers of inflammation and immune status, have significant clinical applications in the prognostic assessment of NPC. The integrated prediction model combining age, TNM staging, SII, and NLR significantly improved the accuracy of survival prediction and provided a reliable basis for individualised treatment of NPC.

Objective Unintentional injuries constitute a significant global public health issue with significant social and economic costs. Previous evidence suggests ambient temperatures are associated with unintentional injury occurrences. However, the impacts of ambient temperature on unintentional injury economic burden have received little research attention. The objective of the study was to examine the association between ambient temperature and economic burden of unintentional injury.Design Time-stratified case-crossover study.Setting This study was performed at Tianjin Hospital, the largest trauma centre in Tianjin, by applying a hospital-based time-stratified case-crossover study.Participants The 12 241 patients admitted with unintentional injuries and meteorological data were collected in Tianjin, China in 2021.Primary and secondary outcome The association between ambient temperature and unintentional injury hospitalisation was evaluated with a distributed lag non-linear model, further temperature-attributable economic burden of unintentional injuries was quantified, and adjusted for demographic characteristics, injury mechanism and injury location of injury.Results The temperatures below 11.5°C were significantly associated with the increased risk of unintentional injury hospitalisation in Tianjin, in 2021. The effect was maximised on the current day. The relatively low temperature was responsible for 25.44% (95% CI 13.74, 33.09) of unintentional injury patients, and was associated with the number of unintentional injury patients (3114, 95% CI 1608, 4036). The relatively low temperature was associated with the excess economic burden for unintentional injury (¥197.52 million, 95% CI 102.00, 256.00; about 27.10 million dollars), accounting for 26.49% of the total economic burden. The cold temperatures generally had greater impacts on males (¥136.46 million, 95% CI 83.28, 172.42; about 18.67 million dollars) and the elderly (¥74.35 million, 95% CI 14.87, 102.14; about 10.24 million dollars).Conclusion The temperature was associated with approximately 3000 unintentional injury patients and ¥200 million (27 million dollars), accounting for 26% of the total economic burden in Tianjin, 2021.

Ureteral endometriosis accounts for about 5 % of urologic endometriosis, with a peak incidence in the age group of 30–35 years, usually with unilateral onset. Because of its insidious onset, often combined with asymptomatic loss of renal function, and the ineffectiveness of medications, surgery is the gold standard of treatment.Thus, here we report a case of ureteral endometriosis with severe hydronephrosis to raise awareness of this condition.

Agricultural non-point source pollution (ANP) had become an important source of water pollution, which seriously restricted the coordinated development of Beijing, Tianjin and Hebei. As the primary agricultural production base in the region of Beijing-Tianjin-Hebei, Hebei had serious ANP. In order to clarify the current status of ANP in Hebei and figure out the main pollution source and areas, ANP load of Hebei from 2000 to 2021 were evaluated by the export coefficient modeling (ECM) and spatial-temporal characteristics were carried out using geographic information system (GIS). In addition, ANP severity and emission characteristics of Hebei in 2021 were evaluated. The results showed that the environmental impact of ANP in southwest area was obviously more serious than that in northeast area of Hebei. Especially, ANP emissions in Hebei showed significant decreasing inflection points in 2007 and 2017, respectively, reaching a minimum by 2021. The TN and TP emissions of ANP in Hebei were 315,026.1 t and 50,323.76 t in 2021, respectively. The contribution of agricultural land, livestock and poultry breeding and rural life to TN and TP emissions were 37%, 34%, 29% and 20%, 61% and 18%, respectively. The ANP pollution mainly came from livestock and poultry breeding in Hebei Province. Based on cluster analysis, cities in Hebei were divided into four types, and the control strategies for ANP environment management were put forward.

Ulcerative colitis (UC), characterized by its recurrent nature, imposes a significant disease burden and compromises the quality of life. Emerging evidence suggests that achieving clinical remission is not sufficient for long-term remission. In pursuit of a favorable prognosis, mucosal healing (MH) has been defined as the target of therapies in UC. This paradigm shift has given rise to the formulation of diverse endoscopic and histological scoring systems, providing distinct definitions for MH. Endoscopic remission (ER) has been widely employed in clinical practice, but it is susceptible to subjective factors related to endoscopists. And there’s growing evidence that histological remission (HR) might be associated with a lower risk of disease flares, but the incorporation of HR as a routine therapeutic endpoint remains a debate. The integration of advanced technology has further enriched the definition of deep MH. Up to now, a universal standardized definition for deep MH in clinical practice is currently lacking. This review will focus on the definition of deep MH, from different dimensions, and analyze strengths and limitations, respectively. Subsequent multiple large-scale trials are needed to validate the concept of deep MH, offering valuable insights into potential benefits for UC patients.

Variable fluorescence measurements provide automatic and rapid estimates of electron-based photosynthesis. However, electron transport rates (ETR) to phytoplankton production vary greatly due to biological physiology and environmental stress along the Changjiang River to the adjacent seawater, where the turbid riverside, nutrient-rich river plume, and seawater are divided by the sediment front and plume front. We assessed the light responses of ETR, 18O-labeled gross primary production (GPP), and O2-based net community production (NCP) during the bloom season at the Changjiang River Estuary. The distribution of phytoplankton and potential photosynthesis efficiency were positively correlated, exhibiting offshore decreasing trends and peaking around the upwelling areas. The conversion factors of ΦGPP (mol e- per mol O2 production) ranged from 0.8 to 31.8, and ΦNCP ranged from 0.9 to 36.9, respectively. Φe: O increased from the nutrient-rich Changjiang diluted water (CDW) to the nutrient-poor seawater. Although ΦGPP and ΦNCP were linearly related to non-photochemical quenching (R2 > 0.5) in the CDW, this relationship was decoupled in offshore seawater due to P-limitation, light stress, and shifts in the phytoplankton community. A better relationship between ΦGPP and ΦNCP was quantified using multiple linear analyses with the light attenuation coefficient (Kd), euphotic depth (Zeu), salinity, nutrients, and temperature (p< 0.001). This improvement in accuracy represents a major step forward for widespread and accurate fluorometry-based GPP and NCP applications at high temporal and spatial resolutions in the future.

Abstract Production of liquid fertilizers containing nitrogenous nutrients and biostimulants from sewage sludge (SS-NB) has been attracting increasing attention due to its excellent fertilization effect and resource recycling attributes. To better understand the functional effects of nutrients and biostimulants in SS-NB on soil, the adsorption capacity and mechanism of straw biochar (SB) and wood chip biochar (WCB) for alkaline and neutral SS-NB components were investigated. The adsorption of total organic carbon (TOC) from alkaline and neutral SS-NB by WCB was 61.14% and 89.73%, respectively, higher than that by SB, which was 56.25% and 83.36%. Moreover, TOC from neutral SS-NB was more readily adsorbed, especially for fulvic and humic acids. SB had a strong adsorption capacity for calcium ions and nitrogen (TKN, nitrate N, protein, amino acid) and released large amounts of P. In addition, WCB and SB showed a strong affinity for macromolecules (proteins) and reducing substances (lignin and lipids) and excellent fixation ability for phytohormones and allelochemicals. However, WCB adsorbed more types of molecular substances than SB while maintaining a high immobilization rate. Analysis of the adsorption mechanism showed that surface amino groups of the biochar were involved in adsorption, while WCB had additionally high adsorption efficiencies through pore adsorption, hydrogen bonding adsorption and pore size-exclusion effects. The study revealed that biochar can be used as an efficient adsorption carrier for SS-NB to improve soil fertility management. Graphical Abstract

Abstract Background Odontogenic cysts/tumor can cause severe bone destruction, which affects maxillofacial function and aesthetics. Meanwhile, metabolic reprogramming is an important hallmark of diseases. Changes in metabolic flow affect all aspects of disease, especially bone-related diseases. At present, the researches on pathogenesis of odontogenic cysts/tumor are mainly focused on the level of gene regulation, but the effects of metabolic alterations on odontogenic cysts/tumor have still underexplored. Materials and methods Imaging analysis was used to evaluate the lesion size of different odontogenic lesions. Tartrate resistant acid phosphatase (TRAP) and immunohistochemistry (IHC) assays were utilized to detect the differences in bone destruction activity in odontogenic cysts and tumors. Furthermore, metabolomics and weighted gene co-expression network analysis (WGCNA) were conducted for the metabolomic features and key metabolite screening, respectively. The effect of ferroptosis inhibition on bone destruction was confirmed by IHC, immunofluorescence, and malondialdehyde colorimetric assay. Results The bone destruction activity of ameloblastoma (AM) was the strongest and the weakest in odontogenic cysts (OC). High-throughput targeted metabolomics was used to map the metabolomic profiles of OC, odontogenic keratocyst (OKC) and AM. WGCNA and differential analysis identified L-cysteine in OKC and AM. Cystathionine γ-lyase (CTH) was further screened by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The functions of L-cysteine were further validated. Finally, we confirmed that CTH affected destructive activities by regulating the sensitivity of epithelial cells to ferroptosis. Conclusion High-throughput targeted metabolomics performed on diseased tissue confirmed the unique alteration of metabolic profiles in OKC and AM. CTH and its metabolite L-cysteine are the key factors regulating destructive activities.

Objective To analyze relationship between autonomic nervous function and cognitive function in elderly patients with Parkinson's disease (PD). Methods A total of 130 elderly patients with PD admitted to The Affiliated Brain Hospital of Nanjing Medical University from January 2020 to December 2022 were included. Hoehn‑Yahr staging was used to evaluate stage of the disease, Unified Parkinson's Disease Rating Scale Ⅲ (UPDRS Ⅲ) was used to evaluate the severity of motor disorders, Scales for Outcomes in Parkinson's Disease ‑ Autonomic (SCOPA ‑ AUT) was used to evaluate autonomic nervous function, Mini‑Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function, Non‑Μotor Symptoms Scale (NMSS) was used to evaluate the severity of nonmotor symptoms. Results According to whether the patients were accompanied by Alzheimer's disease (AD), they were divided into a group with AD (n = 82) and a group without AD (n = 48). The proportion of Hoehn‑Yahr staging 3 to 5 (χ2 = 5.689, P = 0.017), UPDRSⅢ score (t = 21.490, P = 0.000), SCOPA‑AUT score (t = 21.330, P = 0.000), dysregulation of body temperature (χ2 = 8.512, P = 0.004), urinary dysfunction (χ2 = 17.270, P = 0.000), gastrointestinal dysfunction (χ2 = 24.471, P = 0.000), dysregulation of pupil (χ2 = 5.299, P = 0.021), cardiovascular dysfunction (χ2 = 15.355, P = 0.000) and NMSS score (t = 32.309, P = 0.000) in the group with AD were higher than those in the group without AD, the MMSE (t = 4.730, P = 0.000) and MoCA (t = 6.840, P = 0.000) total scores and subtype scores (P = 0.000, for all) in the group with AD were lower than those in the group without AD. Correlation analysis showed that the SCOPA‑AUT score of PD patients with AD was negatively correlated with MMSE and MoCA total scores and subtype scores (P = 0.000, for all). Conclusions The autonomic dysfunction of elderly PD patients with AD is more serious, and the autonomic nervous function is closely related to cognitive function.

Due to various causes, chronic kidney disease（CKD） is characterized by chronic irreversible changes in the structure and function of kidney. The most common pathological manifestation is renal fibrosis. Many studies have demonstrated that injured renal tubular epithelial cells could release a large variety of cytokines to cause extracellular matrix deposition and promote the development of renal fibrosis during CKD. This review summarized the latest studies on the roles of renal tubular epithelial cell injury-related cytokines in CKD. It provided new concepts for clarifying the mechanism and exploring new treatments of CKD.

Abstract Background Approximately 10-15% of inflammatory bowel disease (IBD) patients with overlapping features of ulcerative colitis (UC) and Crohn’s disease (CD) are termed as inflammatory bowel disease unclassified (IBDU). This study aimed to describe the clinical features of IBDU and evaluate the potential associated factors of reclassification. Methods The clinical data of 37 IBDU patients were retrospectively analyzed from November 2012 to November 2020. 74 UC and 74 CD patients were randomly selected and age- and sex-matched with the 37 IBDU patients. Clinical characteristics were compared between the three patient groups. Potential factors associated with the IBDU reclassification were evaluated. Results 60% of IBDU patients displayed rectal-sparing disease, and 70% of them displayed segmental disease. In comparison to UC and CD, the IBDU group demonstrated higher rates of gastrointestinal bleeding (32.4%), intestinal perforation (13.5%), spontaneous blood on endoscopy (51.4%), and progression (56.8%). The inflammation proceeded relatively slowly, manifesting as chronic alterations like pseudopolyps (78.4%) and haustra blunt or disappearance (56.8%). 60% of IBDU patients exhibited crypt abscess, and 16.7% of them exhibited fissuring ulcers or transmural lymphoid inflammation. The proportions of IBDU patients receiving immunosuppressants, surgery, and infliximab were basically the same as those of CD patients. During the 79 (66, 91) months of follow-up, 24.3% of IBDU patients were reclassified as UC, while 21.6% were reclassified as CD. The presence of intestinal hemorrhaging was associated with CD reclassification, while hypoalbuminemia was associated with UC reclassification. Conclusions IBDU may evolve into UC or CD during follow-up, and hemorrhage was associated with CD reclassification. Different from the other two groups, IBDU exhibited a more acute onset and a gradual progression. When an IBD patient presents with transmural inflammation or crypt abscess but lacks transmural lymphoid aggregates or fissuring ulcers, the diagnosis of IBDU should be considered.

Abstract Background and objectives The study investigated the pathogenesis of Yao syndrome (YAOS), a rare systemic autoinflammatory disease associated with the nucleotide-binding oligomerization domain containing 2 (NOD2) gene variants. Methods RNA sequencing analyses were used to detect transcriptomic profile changes. Immunoblot and immunohistochemistry were used to examine the NOD2-mediated inflammatory signaling pathways and ELISA was used to detect cytokines. Results Transcriptome analysis of YAOS revealed NOD-like receptor signaling pathway enrichment. Compared with HCs, P-RIP2, p-p65, p-p38, p-ERK, and p-JNK notably increased in PBMCs of a patient with YAOS. P-RIP2, p-p65, and p-p38 elevated in small intestinal mucosa tissues. P-p65 and p-p38 in synovial tissues from YAOS were higher than those in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Serum interleukin (IL)-6 level along with tumor necrosis factor (TNF)-α and IL-6 secreted from PBMCs were markedly higher in patients with YAOS in comparison to healthy controls (HCs). The supernatants of synovial cells from a patient with YAOS showed substantially higher IL-1β and IL-6 levels than those of RA and OA. Canakinumab therapy of a Q902K heterozygous patient with YAOS resulted in notable clinical improvement. Conclusion Overproduction of pro-inflammatory cytokines and the hyperactivation of NOD2-mediated signaling pathways were found in the NOD2 variant Q902K patient with YAOS. NOD2-RIP2-MAPK pathway might play a pivotal role in the pathogenesis of YAOS. These results provide new perspectives for targeted therapies in YAOS.

Abstract Background Cronkhite-Canada syndrome (CCS) is a rare, nonhereditary disease characterized by diffuse gastrointestinal polyposis and ectodermal abnormalities. Although it has been proposed to be a chronic inflammatory condition, direct evidence of its pathogenesis is lacking. This study aims to investigate the pathophysiology of CCS by analyzing transcriptomic changes in the colonic microenvironment. Methods Next-generation sequencing-based genome-wide transcriptional profiling was performed on colonic hamartomatous polyps from four CCS patients and normal colonic mucosa from four healthy volunteers. Analyses of differential expression and multiple enrichment analyses were conducted from the molecular level to the cellular level. Quantitative real-time PCR (qRT-PCR) was carried out to validate the sequencing accuracy in samples from six CCS patients and six healthy volunteers. Results A total of 543 differentially expressed genes were identified, including an abundance of CC- and CXC-chemokines. Innate immune response-related pathways and processes, such as leukocyte chemotaxis, cytokine production, IL-17, TNF, IL-1 and NF-kB signaling pathways, were prominently enhanced in CCS colonic polyps. Upregulation of wound healing, epithelial-mesenchymal transition, Wnt, and PI3K-Akt signaling pathways were also observed. Enrichment analyses at different levels identified extracellular structure disorganization, dysfunction of the gut mucosal barrier, and increased angiogenesis. Validation by qRT-PCR confirmed increased expression of the LCN2, IL1B, CXCL1, and CXCL3 genes in CCS colonic polyps. Conclusions This case-control whole transcriptome analysis of active CCS colonic hamartomatous polyps revealed intricate molecular pathways, emphasizing the role of the innate immune response, extracellular matrix disorganization, inflammatory cell infiltration, increased angiogenesis, and potential epithelial to mesenchymal transition. These findings supports CCS as a chronic inflammatory condition and sheds light on potential therapeutic targets, paving the way for more effective and personalized management of CCS in the future.

Celiac disease (CD), a gluten‐related disease, is a multi‐system rare disorder mainly involving the gastrointestinal tract. The clinical signs of CD are exceedingly heterogeneous, which increases the difficulty of clinical differential diagnosis. Neurological manifestations are one of the non‐classical CD symptoms. As some patients present only neurological symptoms at early stages, the diagnosis of CD is always delayed. Correct diagnosis and management could decrease patient morbidity and deaths. A 32‐year‐old male was admitted to the hospital due to progressive muscle atrophy of both lower limbs and lumbar stiffness. Based on positive gluten‐sensitive enteropathy autoantibody profiles and gastroscopy foundation, the diagnosis of CD was established. The patient was instructed to gluten‐free diet. The antibody titer of gluten‐sensitive enteropathy autoantibodies decreased, and the patient's symptoms alleviated. We emphasize the importance of CD screening in patients with neurological disorders of unknown aetiology.

The Qinghai-Tibet Plateau stands as one of the most ecologically fragile and biodiversity-rich regions globally. Understanding the distribution of different taxa and their relationship with environmental factors is crucial for effective conservation and sustainable management. Polytrichaceae, a significant bryophyte family widely distributed in Tibet, displays distinct structural, morphological, and phylogenetic traits compared to other mosses. Despite its importance, the distribution of Polytrichaceae in Tibet and its correlation with environmental factors have yet to be explored. In this study, we used an optimized Maximum Entropy (MaxEnt) model to explore the potential suitable habitats of Polytrichaceae in Tibet, aiming to clarify their geographic distribution pattern as well as the key environmental influence factors. The model had high accuracy with an average Area Under the Curve (AUC) of 0.933 and True Skill Statistics (TSS) value of 0.789. The results showed that the potential suitability habitats of Polytrichaceae were mainly located in southeastern Tibet, and the low suitable, moderately suitable, and highly suitable habitats accounted for 12.53 %, 6.84 %, and 3.31 % of the total area of Tibet respectively. Unsuitable habitats were mainly located in northwestern Tibet, accounting for about 77.32 %. In Tibet, temperature factors (Mean Temperature of Coldest Quarter (Bio11) and Annual Mean Temperature (Bio1)) played a pivotal role in determining the potential suitable habitats for Polytrichaceae, and elevation, precipitation, and vegetation coverage also had an important influence. The family preferred warm, moist and densely vegetated habitats in Tibet. This study enriched our ecological understanding of bryophyte ecology in this region and provided data-driven support for biodiversity conservation and ecosystem management in Tibet.

BackgroundDespite extensive research on hyperuricemia (HUA) in adults, there remains a dearth of studies examining this condition in youth. Consequently, our objective was to investigate the prevalence of HUA among youth in the United States, as well as identify the corresponding risk factors.MethodsThis study employed a nationally representative subsample of 1,051 youth aged 13–20 from the US National Health and Nutrition Examination Survey (NHANES) conducted between January 2017 and March 2020. Univariate and multivariate techniques were utilized to examine the association between HUA and obesity, dietary nutrients, liver and kidney function, glucose and lipid metabolism, inflammation, and other indicators in the adolescent population.ResultsThe study encompassed a cohort of 1,051 youth aged 13–20 years, comprising 538 boys and 513 girls. The overall prevalence of HUA was found to be 7% (74 out of 1,051). Univariate analysis revealed that the HUA group exhibited greater age, body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). Additionally, the prevalence of obesity was significantly higher in the HUA group compared to the non- HUA group (all p 0.05).ConclusionHigh BMI remains a major risk factor for HUA in US youth aged 13–20 years, and ALT and Cr levels should be closely monitored along with serum uric acid.

Background and PurposeUntil now, it has been difficult to accurately predict the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC). A novel indicator, the lung immune prognostic index (LIPI), has shown relatively high prognostic value in patients with solid cancer. Therefore, this study aimed to further identify the association between LIPI and the survival of patients with NSCLC who receive immune checkpoint inhibitors (ICIs).MethodsSeveral electronic databases were searched for available publications up to April 23, 2023. Immunotherapy outcomes included overall survival (OS), progression-free survival (PFS), and hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analysis based on the study design and comparison of the LIPI was conducted.ResultsIn this meta-analysis, 21 studies with 9,010 patients were included in this meta-analysis. The pooled results demonstrated that elevated LIPI was significantly associated with poor OS (HR = 2.50, 95% CI:2.09–2.99, p < 0.001) and PFS (HR = 1.77, 95% CI:1.64–1.91, p < 0.001). Subgroup analyses stratified by study design (retrospective vs. prospective) and comparison of LIPI (1 vs. 0, 2 vs. 0, 1–2 vs. 0, 2 vs. 1 vs. 0, 2 vs. 0–1 and 2 vs. 1) showed similar results.ConclusionLIPI could serve as a novel and reliable prognostic factor in NSCLC treated with ICIs, and elevated LIPI predicts worse prognosis.

BackgroundThough considerable studies suggesting connections between micronutrients and pregnancy complications, current evidence remains inconsistent and lacks causative confirmation. Our study aimed to explore the causal links between them with a two-sample Mendelian randomization (MR) analysis.MethodsGenome-wide association studies (GWAS) data for circulating micronutrients were sourced from GWAS Catalog consortium and PubMed, while data for pregnancy outcomes, including gestational diabetes mellitus (GDM), gestational hypertension (GH), spontaneous abortion (SA), preterm birth (PTB), and stillbirth (SB), were retrieved from the UK Biobank and FinnGen consortia. Causal effects were appraised using inverse variance weighted (IVW), weighted median (WM), and MR-Egger, followed by sensitivity analyses and meta-analysis for validation.ResultsGenetically predicted higher vitamin E (OR = 0.993, 95% CI 0.987–0.998; p = 0.005) levels were inversely associated with SA risk. Consistent results were obtained in meta-analysis (OR = 0.99, 95% CI 0.99–1.00; p = 0.005). Besides, a potential positive causality between genetic predisposition to vitamin B12 and SB was identified in both IVW (OR = 0.974, 95% CI 0.953–0.996; p = 0.018) and WM analysis (OR = 0.965, 95% CI 0.939–0.993; p = 0.013). However, no causal relationships were observed between other analyzed circulating micronutrients and pregnancy complications.ConclusionThis study offers compelling evidence of causal associations between circulating levels of vitamins E, B12 and the risk of SA and SB, respectively. These findings are pivotal for pregnancy complications screening and prevention, potentially guiding clinical practice and public health policies toward targeted nutritional interventions.

The integration of distributed generation resources in power systems offers various advantages, such as peak load management and reduced transmission line congestion. However, it also introduces challenges related to voltage stability. This paper presents a novel multi-objective model for optimizing the allocation of solar resources in radial distribution systems. The model aims to achieve an optimal voltage profile, minimize losses, and maximize penetration levels. To address the conflicting nature of these objectives, a refined multi-objective slime mold algorithm (MOSMA) is proposed. This algorithm demonstrates exceptional capabilities in finding Pareto fronts, avoiding local optima, and effectively solving multi-objective problems compared to other optimization methods. Additionally, the corrected social hierarchy method is integrated to enhance performance. The proposed method is evaluated using a standard system under various operational conditions, showing superior results in terms of maintaining an acceptable voltage profile and significantly reducing losses. The study reveals that while losses decrease for penetration levels ranging from low to medium, they start to increase for levels exceeding 100 %. Notably, the proposed method achieves approximately 12 % system efficiency improvement, as measured by the voltage profile, at a penetration level of 300 %. These findings highlight the effectiveness of the proposed method, even at high penetration levels, surpassing other optimization approaches based on the inverse generation distance parameter.

BackgroundTo the best of our knowledge, numerous observational studies have linked pregnancy complications to increased risks of diabetes and cardiovascular disease (CVD), causal evidence remains lacking. Our aim was to estimate the association of adverse pregnancy outcomes with diabetes and cardiovascular diseases.MethodsA two-sample Mendelian randomization (MR) analysis was employed, which is not subject to potential reverse causality. Data for pregnancy complications were obtained from the FinnGen consortium. For primary analysis, outcome data on diabetes, related traits, stroke, and coronary heart disease (CHD) were extracted from the GWAS Catalog, MAGIC, MEGASTROKE, and CARDIoGRAMplusC4D consortium. The MAGIC and UKB consortium datasets were used for replication and meta-analysis. Causal effects were appraised using inverse variance weighted (IVW), weighted median (WM), and MR-Egger. Sensitivity analyses were implemented with Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out (LOO) analysis and the funnel plot.ResultsGenetically predicted gestational diabetes mellitus (GDM) was causally associated with an increased diabetes risk (OR=1.01, 95% CI=1–1.01, P

Study region: The largest inland river basin in China (the Tarim River Basin) Study focus: This study introduces a novel classification scheme for dry and warm snow droughts with focus on their duration, severity, and intensity. The Nonparametric Standardized SWE Index (NSWEI) and the Standardized Precipitation Index (SPI) were employed to assess these drought types. The optimal parameters-based geographical detector (OPGD) model and machine learning (including random forest model and Shapley-XGBoost algorithm) were applied to reveal the spatial and time dynamic driving forces of droughts. New hydrological insights for the regions: Results indicated that warm-type droughts occurred more frequently and with greater intensity, exhibiting a larger spatial coverage compared to dry-type droughts, which can be attributed to warm-type droughts dominated by temperature and vapor pressure deficit, whereas dry-type are predominantly influenced by relative humidity and solar radiation. Moreover, the dynamics of snow droughts exhibited a contrasting pattern between the south (experiencing an upward trend) and the north (experiencing a descending trend). In the south, dry-type droughts were exacerbated by the strength of North Pacific Oscillation (PDO)-precipitation coupling, while warm-type droughts are influenced by the strength of North Atlantic Oscillation (NAO)-precipitation coupling and El Niño Southern Oscillation (ENSO)-precipitation.

Abstract Background Human dermal fibroblasts (HDFs) are essential in the processes of skin ageing and wound healing. However, the underlying mechanism of HDFs in skin healing of the elderly has not been well defined. This study aims to elucidate the mechanisms of HDFs senescence and how senescent HDFs affect wound healing in aged skin. Methods The expression and function of sperm equatorial segment protein 1 (SPESP1) in skin ageing were evaluated via in vivo and in vitro experiments. To delve into the potential molecular mechanisms by which SPESP1 influences skin ageing, a combination of techniques was employed, including proteomics, RNA sequencing, immunoprecipitation, chromatin immunoprecipitation and liquid chromatography‐mass spectrometry analyses. Clearance of senescent cells by dasatinib plus quercetin (D+Q) was investigated to explore the role of SPESP1‐induced senescent HDFs in wound healing. Results Here, we define the critical role of SPESP1 in ameliorating HDFs senescence and retarding the skin ageing process. Mechanistic studies demonstrate that SPESP1 directly binds to methyl‐binding protein, leading to Decorin demethylation and subsequently upregulation of its expression. Moreover, SPESP1 knockdown delays wound healing in young mice and SPESP1 overexpression induces wound healing in old mice. Notably, pharmacogenetic clearance of senescent cells by D+Q improved wound healing in SPESP1 knockdown skin. Conclusions Taken together, these findings reveal the critical role of SPESP1 in skin ageing and wound healing, expecting to facilitate the development of anti‐ageing strategies and improve wound healing in the elderly.

In modern ecological systems, the overuse and misuse of antibiotics have escalated the prevalence of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs), positioning them as emerging environmental contaminants. Notably, composting serves as a sustainable method to recycle agricultural waste into nutrient-rich fertilizer while potentially reducing ARGs and MGEs. This study conducted a 47-day composting experiment using pig manure and corn straw, supplemented with chitin and N-Acetyl-D-glucosamine, to explore the impact of these additives on the dynamics of ARGs and MGEs, and to unravel the interplay between these genetic elements and microbial communities in pig manure composting. Results showed that adding 5% chitin into composting significantly postponed thermophilic phase, yet enhanced the removal efficiency of total ARGs and MGEs by over 20% compared to the control. Additionally, the addition of N-Acetyl-D-glucosamine significantly increased the abundance of tetracycline-resistant and sulfonamide-resistant genes, as well as MGEs. High-throughput sequencing revealed that N-Acetyl-D-glucosamine enhanced bacterial α-diversity, providing diverse hosts for ARGs and MGEs. Resistance mechanisms, predominantly efflux pumps and antibiotic deactivation, played a pivotal role in shaping the resistome of composting process. Co-occurrence network analysis identified the key bacterial phyla Proteobacteria, Firmicutes, Gemmatimonadota, and Myxococcota in ARGs and MGEs transformation and dissemination. Redundancy analysis indicated that physicochemical factors, particularly the carbon-to-nitrogen ratio emerged as critical variables influencing ARGs and MGEs. The findings lay a foundation for the developing microbial regulation method to reduce the risks of ARGs in animal manure composts.

Predicting, issuing early warnings, and assessing risks associated with unnatural epidemics (UEs) present significant challenges. These tasks also represent key areas of focus within the field of prevention and control research for UEs. A scoping review was conducted using databases such as PubMed, Web of Science, Scopus, and Embase, from inception to 31 December 2023. Sixty-six studies met the inclusion criteria. Two types of models (data-driven and mechanistic-based models) and a class of analysis tools for risk assessment of UEs were identified. The validation part of models involved calibration, improvement, and comparison. Three surveillance systems (event-based, indicator-based, and hybrid) were reported for monitoring UEs. In the current study, mathematical models and analysis tools suggest a distinction between natural epidemics and UEs in selecting model parameters and warning thresholds. Future research should consider combining a mechanistic-based model with a data-driven model and learning to pursue time-varying, high-precision risk assessment capabilities.

To address the challenges of road extraction in high-resolution remote sensing images, this paper presents an enhanced UNet++ road extraction method that incorporates CBAM. The original UNet++ network is referenced, and the loss function is improved by introducing a new joint loss function. The enhanced UNet++ network utilizes an attention mechanism to enhance the network’s ability to identify road features, thereby improving the accuracy of road extraction. Additionally, a new joint loss function is employed to enhance the network’s stability and further improve its road extraction capability. Experimental validation is performed on the Massachusetts roads dataset and DeepGlobal road dataset. The experimental results demonstrate that this method outperforms U-Net, SegNet, and UNet++ networks in terms of IoU, Recall, OA, and Kappa. Specifically, on the Massachusetts road dataset, the OA and Kappa values are 94.92% and 0.9202, respectively. On the DeepGlobal road dataset, the OA and Kappa values for this algorithm are 98.12% and 0.9515, respectively. The ablation experiment confirms the effectiveness of the proposed enhancements. In conclusion, this paper presents a method that effectively extracts roads from high-resolution remote sensing images, exhibits a certain level of generalization ability, and can provide valuable support for road protection and planning.

A new pixel circuit consisting of eleven n-type IGZO transistors (TFTs) and four capacitors is proposed and applied for micro light emitting diode (MLED) displays. The circuit is driven by pulse hybrid modulation (PHM), combining pulse amplitude modulation (PAM) and pulse width modulation (PWM). In purpose, high grayscales are achieved by PAM mode and low grayscales are achieved by PWM mode, which keep the driving current of LED out of the small value range so as to avoid unstable luminance performance. It is conducted that the MLED display driven by PHM demonstrate a stable luminance at low grayscale with well suppressed luminance errors of over 30% decrease, in comparison with the display driven by PAM. Moreover, both threshold voltage (VTH) shifts of driving TFTs for PAM mode and PWM mode could be well compensated in this circuit. As revealed by simulations, the driving current variations of LED could be retained within 10% when VTH shifts in the ranges from −1 to 2 V for PAM driving TFT and from −1 to 1.5 V for PWM driving TFT, respectively. In practice, a good brightness uniformity over 90% after 240-hours aging of the MLED display could be realized.

Abstract Background Tar is the main toxic of cigarettes, and its effect on atherosclerosis progression and the underlying mechanisms remain largely unknown. Vascular smooth muscle cells (VSMCs) play a key role in atherogenesis and plaque vulnerability. The present study sought to investigate the mechanism of atherosclerosis progression through tar-induced VSMC necroptosis, a recently described form of necrosis. Methods The effect of tar on atherosclerosis progression and VSMC necroptosis was examined in ApoE−/− mice and cultured VSMCs. The role of necroptosis in tar-induced plaque development was evaluated in RIPK3-deletion mice (ApoE−/−RIPK3−/−). The key proteins of necroptosis in carotid plaques of smokers and non-smokers were also examined. Quantitative proteomics of mice aortas was conducted to further investigate the underlying mechanism. Pharmacological approaches were then applied to modulate the expression of targets to verify the regulatory process of tar-induced necroptosis. Results Tar administration led to increased atherosclerotic plaque area and reduced collagen and VSMCs in ApoE−/− mice. The expression of RIPK1、RIPK3、and MLKL in VSMCs of plaques were all increased in tar-exposed mice and smokers. RIPK3 deletion protected against VSMC loss and plaque progression stimulated by tar. In mechanistic studies, quantitative proteomics analysis of ApoE−/− mice aortas suggested that tar triggered endoplasmic reticulum (ER) stress. PERK-eIF2α-CHOP axis was activated in tar-treated VSMCs and atherosclerotic plaque. Inhibition of ER stress using 4PBA significantly reduced plaque progression and VSMC necroptosis. Further study revealed that ER stress resulted in calcium (Ca2+) release into mitochondria and cytoplasm. Elevated Ca2+ levels lead to mitochondrial dysfunction and excessive reactive oxygen species (ROS) production, which consequently promote RIPK3-dependent necroptosis. In addition, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activated by cytosolic Ca2+ overload binds to RIPK3, accounting for necroptosis. Conclusion The findings revealed that cigarette tar promoted atherosclerosis progression by inducing RIPK3-dependent VSMC necroptosis and identified novel avenues of ER stress and Ca2+ overload.

Abstract To investigate the occurrence and 90-day mortality of cancer patients following unplanned admission to the intensive care unit (ICU), as well as to develop a risk prediction model for their 90-day prognosis. We prospectively analyzed data from cancer patients who were admitted to the ICU without prior planning within the past 7 days, specifically between May 12, 2021, and July 12, 2021. The patients were grouped based on their 90-day survival status, and the aim was to identify the risk factors influencing their survival status. A total of 1488 cases were included in the study, with an average age of 63.2 ± 12.4 years. The most common reason for ICU admission was sepsis (n = 940, 63.2%). During their ICU stay, 29.7% of patients required vasoactive drug support (n = 442), 39.8% needed invasive mechanical ventilation support (n = 592), and 82 patients (5.5%) received renal replacement therapy. We conducted a multivariate COX proportional hazards model analysis, which revealed that BMI and a history of hypertension were protective factors. On the other hand, antitumor treatment within the 3 months prior to admission, transfer from the emergency department, general ward, or external hospital, high APACHE score, diagnosis of shock and respiratory failure, receiving invasive ventilation, and experiencing acute kidney injury (AKI) were identified as risk factors for poor prognosis within 90 days after ICU admission. The average length of stay in the ICU was 4 days, while the hospital stay duration was 18 days. A total of 415 patients died within 90 days after ICU admission, resulting in a mortality rate of 27.9%. We selected 8 indicators to construct the predictive model, which demonstrated good discrimination and calibration. The prognosis of cancer patients who are unplanned transferred to the ICU is generally poor. Assessing the risk factors and developing a risk prediction model for these patients can play a significant role in evaluating their prognosis.

Abstract Background Integrative Chinese and Western medicine (ICWM) is commonly used for the treatment of ulcerative colitis (UC) in clinical practice. However, it is unclear whether the details of ICWM interventions, such as selection rationale, implementation design, and potential interactions, were adequately reported. Therefore, this study aimed to assess the quality of reporting in the ICWM interventional randomized controlled trials (RCTs) of UC and to identify the common problems if any. Methods Through a search of 10 international electronic databases, we identified RCTs of UC with ICWM interventions published in English or Chinese from the inception date of each database up to 16 June 2023. Literature screening was strictly conducted based on the inclusion and exclusion criteria of the Population, Concept, and Context (PCC) framework. The general characteristics of the included studies were described. The quality of reporting was assessed according to three checklists, including the CONSORT (Consolidated Standards of Reporting Trials) with 36 items (except for one item 1b about abstract), the CONSORT for Abstracts (17 items), and a self-designed ICWM-related checklist (27 items covering design rationale, intervention details, outcome assessments, and analysis). The reporting scores of RCTs published before and after 2010 were compared. Results A total of 1458 eligible RCTs were included. For the reporting compliance, the median score (interquartile ranges) of the CONSORT (72 score in total), the CONSORT for Abstract (34 score), and ICWM-related (54 score) items was 21 (18–25), 13 (12–15), and 18 (15–21), respectively. Although the time period comparisons showed that reporting quality of included publications improved significantly after the CONSORT 2010 issued (P

Objective: To express the protein HmpA of Salmonella paratyphi A in prokaryotes, and perform bioinformatics analysis on it to provide a theoretical reference for studying the effect of this protein on the nitric oxide (NO) signaling pathway in the host. Methods: The hmpA gene was amplified by PCR and subcloned into the T-vector. Then the expression vector pNdeI-hmpA was constructed and transformed into BL21 (DE3). After induced by IPTG, the recombinant protein expression form was assessed by SDS-PAGE. HmpA was purified using Histrap preload column and identified by Western blot. Bioinformatics technology was used to analyze the characteristics of HmpA. Results: The prokaryotic expression vector pNdeI-hmpA was successfully constructed. HmpA coexisted in the inclusion body and soluble forms under low temperatures after being induced with IPTG. The purified HmpA protein could be detected by the anti-His antibody. Bioinformatics analysis suggested that HmpA was a hydrophilic protein with no transmembrane structural domain or signal peptide. The secondary structure of this protein was mainly composed of α-helix with irregular convolutions, and the tertiary structure model was similar to a ring. The protein structural domain analysis showed that HmpA contains one functional structural domain belonging to the PRK13289 superfamily. There were 32 phosphorylation sites in HmpA. Associated with multiple Salmonella proteases or transcription factors that degrade nitrates and killer NO. Conclusion: This study successfully obtained Salmonella paratyphi A HmpA protein by genetic engineering technology and predicted part of its biological characteristics by bioinformatics methods, which would provide theoretical support for the subsequent uncovering of the influence of HmpA of Salmonella paratyphi A on the nitric oxide signaling pathway in the host.

Abstract. Background:. Human neutrophil lipocalin (HNL) has been used extensively to differentiate acute bacterial infection from febrile diseases as a biomarker to reflect the activation of the neutrophil. The serum HNL levels in the adult-onset Still's disease (AOSD) patients with and without infection, as well as the healthy controls (HCs), were analyzed statistically in this study to evaluate the value of HNL for the diagnosis of AOSD. Methods:. A total of 129 AOSD patients were enrolled, from whom blood samples were drawn and the AOSD diagnosis was confirmed through the review of the medical records, where the systemic score, demographic characteristics, clinical manifestations, and laboratory parameters were also collected for the patients; in addition, a total of 40 HCs were recruited among the blood donors from the healthcare center with the relevant information collected. The HNL test was done for the blood samples with the enzyme-linked immunosorbent assay and the analyses were done for the correlations of HNL with clinical manifestations and diagnostic effectiveness. Results:. The serum HNL increased significantly in the patients with only AOSD as compared with that in the HCs (139.76 ± 8.99 ng/mL vs. 55.92 ± 6.12 ng/mL; P

Abstract Background Cultivated Hippeastrum × hybridum is a popular ornamental plant with large and colorful flowers, long flowering duration, and high commercial value. As its main ornamental feature, its flower color is related to the anthocyanin content in the tepals. However, the molecular regulatory mechanisms of anthocyanin biosynthesis in H. × hybridum have not yet been elucidated. Results In the present study, 12 cDNA libraries of four stages of H.× hybridum ‘Royal Velvet’ tepal development were used for RNA-seq, obtaining 79.83 gigabases (GB) of clean data. The data were assembled into 148,453 unigenes, and 11,262 differentially expressed genes were identified. Forty key enzymes participating in anthocyanin biosynthesis were investigated, and the results showed that most of the anthocyanin structural genes were expressed at low levels in S1 and were markedly upregulated in S2 and S3. The expression profiles of 12 selected genes were verified by qRT-PCR. Furthermore, the R2R3-MYB transcription factor (TF), HpMYB1, involved in the regulation of anthocyanin biosynthesis was identified by sequence, expression pattern, and subcellular localization analyses. Its overexpression in tobacco significantly increased the anthocyanin levels in various tissues and activated anthocyanin-related genes. Conclusions Using RNA-seq technology, we successfully identified a potential R2R3-MYB gene, HpMYB1, that regulates anthocyanin biosynthesis in H.× hybridum ‘Royal Velvet’. Our findings provide basic transcript information and valuable transcriptome data for further identification of key genes involved in anthocyanin biosynthesis and can be applied in the artificial breeding of new H. × hybridum cultivars with enhanced ornamental value.

Abstract Background and aims Common variable immunodeficiency disorder (CVID) patients may have gastrointestinal (GI) involvement and suffer from infections, which are poorly understood. This study aimed to evaluate the clinical, endoscopic, and histopathological features of CVID patients with GI symptoms and determine their correlation with infections. Methods We performed a retrospective study on 21 CVID patients with GI symptoms who underwent endoscopic examination in Peking Union Medical College Hospital from 2000 to 2020. The clinical, infectious, endoscopic, and histopathological features were reassessed. Results Chronic diarrhea was the most prevalent GI symptom, observed in 95.2% of our CVID cohort. Over 85% of patients had low body weight and malabsorption. Small bowel villous atrophy was found in 90.5% of patients under endoscopy and mostly confirmed by histopathology. GI infections were identified in 9 (42.9%) patients. Of these, 7 patients with diffuse and obvious nodular lymphoid hyperplasia (NLH) of small bowel under endoscopy had significantly higher infection rate (85.7% vs 21.4%, p

Rheumatoid arthritis is a chronic, systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate. Several drugs have been used for the treatment of rheumatoid arthritis, but their use is limited by suboptimal bioavailability, serious adverse effects, and nonnegligible first-pass effects. In contrast, transdermal drug delivery systems (TDDSs) can avoid these drawbacks and improve patient compliance, making them a promising option for the treatment of rheumatoid arthritis (RA). Of course, TDDSs also face unique challenges, as the physiological barrier of the skin makes drug delivery somewhat limited. To overcome this barrier and maximize drug delivery efficiency, TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology, and different generations of TDDSs have been derived, which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery. In this review, we summarize the different generations of transdermal drug delivery systems, the corresponding transdermal strategies, and their applications in the treatment of RA.

A high-precision focusing mechanism was designed using a flexible hinge to address the demand for precise focusing in space cameras. Firstly, a finite element model of the liner guideway was created using Hertz contact theory, and the accuracy of the model was confirmed using the “flip method”. Subsequently, the flexible hinge was optimized by a mix of topological and integrated optimization. The simulation results demonstrated that the improved flexible hinge successfully eliminates interference between the liner guideway and the screw, minimizes the effects of initial assembly mistakes, and greatly reduces the tilt error of the focusing mechanism. Afterward, the focusing mechanism was subjected to a vibration test, which showed that its first-order fundamental frequency reached 163.28 Hz. This frequency is sufficiently high to minimize the risk of resonance during the launch phase. Ultimately, the tilt error of the focusing mechanism was assessed using both a rigid connector and a flexible hinge. The findings demonstrated that implementing the flexible hinge resulted in a 55.7% decrease in the range of Δθz and a 55.22% reduction in the standard deviation, effectively fulfilling the specified design requirements. This study indicates that the inclusion of a flexible hinge in the focusing mechanism leads to a substantial decrease in tilt error.