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Abstract This study aimed to develop a PANoptosis-related gene prognostic index (PANGPI) to explore its potential value in predicting the prognosis and immunotherapy response of diffuse large B-cell lymphoma (DLBCL). Differentially expressed genes of DLBCL from GEO databases were analyzed and mapped to the PANoptosis gene set. The independent prognostic value of the PANGPI signature was evaluated using LASSO Cox regression and multivariate Cox regression. Additionally, the tumor infiltrating lymphocyte (TIL) characteristics and mutation landscape of both subgroups were evaluated, and drug sensitivity was predicted using the GDSC database. Furthermore, in silico docking and molecular dynamic simulation studies were presented to elucidate the mode of interaction of these predicted drugs. The PANGPI risk score was an independent risk factor for the prognosis of patients with DLBCL and exhibited good prognostic predictive performance. Furthermore, the cytolytic activity of the TILs was positively correlated with the PANGPI scores. Additionally, the PANGPI enabled the identification of 3 chemotherapeutic agents, including BMS-536924, Gefitinib, Navitoclax for DLBCL patients in the high-risk group. We established a novel PANoptosis-related gene subtyping system in DLBCL, which could shed a novel light on the development of new biomarkers for DLBCL.

Context The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown.Objective This study explores the mechanisms of GGD against cardiac hypertrophy.Materials and methods Network pharmacology analysis was carried out to identify the potential targets of GGD. In vivo experiments, C57BL/6J mice were divided into Con, phenylephrine (PE, 10 mg/kg/d), 2-chloroadenosine (CADO, the stable analogue of adenosine, 2 mg/kg/d), GGD (5.4 g/kg/d) and GGD (5.4 g/kg/d) + CGS15943 (a nonselective adenosine receptor antagonist, 4 mg/kg/d). In vitro experiments, primary neonatal rat cardiomyocytes (NRCM) were divided into Con, PE (100 µM), CADO (5 µM), GGD (10−5 g/mL) and GGD (10−5 g/mL) + CGS15943 (5 µM). Ultrasound, H&E and Masson staining, hypertrophic genes expression and cell surface area were conducted to verify the GGD efficacy. Adenosine receptors (ADORs) expression were tested via real-time polymerase chain reaction (PCR), western blotting and immunofluorescence analysis.Results Network pharmacology identified ADORs among those of the core targets of GGD. In vitro experiments demonstrated that GGD attenuated PE-induced increased surface area (with an EC50 of 5.484 × 10−6 g/mL). In vivo data shown that GGD attenuated PE-induced ventricular wall thickening. In vitro and in vivo data indicated that GGD alleviated PE-induced hypertrophic gene expression (e.g., ANP, BNP and MYH7/MYH6), A1AR over-expression and A2aAR down-expression. Moreover, CADO exerts effects similar to GGD, whereas CGS15943 eliminated most effects of GGD.Discussion and conclusions Our findings suggest the mechanism by which GGD inhibits cardiac hypertrophy, highlighting regulation of ADORs as a potential therapeutic strategy for HF.

Abstract Background The impact of the Plan-Do-Check-Act (PDCA) cycle in improving the timeliness of electronic medical record documentation (EMRd) remains uncertain. EMRd that is completed beyond the specified time is classified as late EMRd, while unqualified EMRd refers to electronic medical records with important sections that are not completed on time according to the Chinese Basic Norms of Medical Records Writing. This study aimed to evaluate the effectiveness of PDCA management in improving the timeliness of EMRd among resident doctors. Method This study utilized a before and after design. Resident doctors rotating in the Head and Neck Oncology Department of West China Hospital, Sichuan University, from November 2021 to August 2022 were classified as the control group and did not receive specific training on the timeliness of EMRd. Those rotating from September 2022 to June 2023 were assigned to the PDCA group, which was managed using the PDCA cycle. The effectiveness of PDCA cycle management was evaluated by comparing the incidence of late EMRd and unqualified EMRd between two groups. Univariate and multivariate binary logistic regression analyses were conducted tocontrol for confounding factors. Results A total of 245 resident doctors were included, with 162 doctors in the PDCA group and 152 doctors in the control group. The incidences of late EMRd (5.40% vs. 2.56%, P = 0.005) and unqualified EMRd (1.05% vs. 0.00%, P

Abstract Objective To investigate the effects of zoledronic acid on muscle metabolism in mice with osteoporosis and sarcopenia and elucidate the possible underlying mechanism. Methods Twenty-four 8-week-old male C57BL/6J mice were randomly divided into four groups: non-suspension (N-SUS), suspension (SUS), suspension + zoledronic acid (ZA), and suspension + PTH(PTH) groups. Equal doses of saline, zoledronic acid, and PTH were administered subcutaneously. After 4 weeks, the mice were sacrificed, and body weight and muscle mass (gastrocnemius and soleus) were measured, the right tibia of mice was taken for micro-CT examination, and the muscle specimens were analyzed using HE staining, ATPase staining, western blotting, and real-time PCR. Results Compared with the N-SUS group, the bone mineral density (BMD), trabecular bone relative volume (BV/TV) and trabecular bone number (Tb.N) were significantly decreased in the SUS group (P

Abstract This study aimed to identify the specific site of pulmonary vein conduction recovery after radiofrequency ablation (RFA) of atrial fibrillation (AF) for improved outcomes and reduced recurrence. Patients who underwent RFA for AF at our institution were included. The ablation procedure was guided by the ablation index (AI) and left, and right atrial pressures were monitored before and after ablation. Additionally, the recovery time of the sinoatrial node under Burst 400/300 ms stimulation was examined. Among 60 repeat procedure patients, 48 had paroxysmal and 12 had persistent AF. The recovery sites were 36.6% in the left anterior superior, 35% in the right anterior superior, 20% in the left anterior inferior, 20% in the right anterior inferior, 13.3% in the right top, and 11.6% in the left top. Preoperative and postoperative left and right atrial pressures were significantly higher in the persistent AF group compared with the paroxysmal AF group (P

BackgroundA large body of cross-sectional studies have indicated a correlation between exposure to benzene series and increased rates of menstrual abnormalities in female workers, but these findings are confusing as evidence in the field of preventive medicine. ObjectiveTo provide a more rigorous scientific basis for early prevention of reproductive function impairment through systematic review of independent studies. MethodsA comprehensive search was conducted for scientific articles published between January 1987 and July 2022, encompassing databases such as PubMed, Medline, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and CQVIP. A meta-analysis was conducted on literature that met the stringent criteria for case-control studies, featuring well-defined and consistent datasets. A meticulous investigation was executed to ascertain the collective odds ratio (OR) linked to menstrual abnormalities, encompassing diverse categories such as component, dosage, cumulative exposure dosage, and age groups. The prevalence and corresponding risk fractions were estimated by calculating frequency distributions and attributing risk percentages (AR). ResultsA total of 53 papers of case-control studies were included in the meta-analysis, involving 27068 benzene series-exposed female workers and 22857 control female workers. During inhalation exposure to benzene series, benzene, toluene, and xylene all increased the risk of female menstrual abnormalities (OR=3.46, 95%CI: 2.79, 4.30, AR=29.37%). The OR value elevated with the increase of joint exposure concentration (OR=2.57-4.33), the OR value of the low cumulative exposure group was lower than that of the high cumulative exposure group (OR=2.81 vs 3.86, P < 0.01), and the OR value of the group aged 18 to 36 years old was higher than that of the group aged 18 to 45 years old (OR=5.83 vs 2.93, P < 0.01). The OR value discrepancy was apparent among the groups with single and multi-components of benzene, toluene, and xylene at different concentrations (OR=2.39-6.42, 95%CI: 1.26, 9.06). The symptom dimensions of menstrual abnormalities with a higher AR were abnormal menstrual volume (AR=47.12%), followed by abnormal menstrual cycle (AR=38.68%). The symptoms that were greatly influenced by the exposures were: irregular menstrual cycle (OR=3.33, 95%CI: 2.94, 3.79, AR=51.25%, n=1103), menorrhagia (OR=3.02, 95%CI: 2.76, 3.30, AR=46.73%, n=2262), dysmenorrhea (OR=3.22, 95%CI: 2.69, 3.84, AR=44.18%, n=3183), and prolonged menstrual duration (OR=2.20, 95%CI: 1.99, 2.43, AR=37.02%, n=1452). Conclusion Through inhalation exposure to benzene series, a higher concentration of combined benzene, toluene, and xylenes may increase the risk of menstrual abnormalities in female workers of childbearing age. The OR value of menstrual abnormalities is varied by chemical composition, exposure dose, cumulative exposure dose, and age. Volume and cycle of menstruation are affected by the exposure, and the most common symptoms are dysmenorrhea, menorrhagia, irregular cycle.

Abstract Ectomycorrhizal fungi (EMF) are key symbiotic microbial components for the growth and health of trees in urban greenspace habitats (UGSHs). However, the current understanding of EMF diversity in UGSHs remains poor. Therefore, in this study, using morphological classification and molecular identification, we aimed to investigate EMF diversity in three EMF host plants: Cedrus deodara in the roadside green belt, and C. deodara, Pinus massoniana, and Salix babylonica in the park roadside green belt, in Guiyang, China. A total of 62 EMF Operational Taxonomic Units (OTUs) were identified, including 13 EMF OTUs in the C. deodara roadside green belt, and 23, 31, and 9 EMF OTUs in the park green belts. C. deodara, P. massoniana, and S. babylonica were respectively identified in park green belts. Ascomycota and Basidiomycota were the dominant phylum in the EMF communities in roadside and park green habitat, respectively. The Shannon and Simpson indexes of the C. deodara EMF community in the park green belt were higher than those in the roadside green belt. EMF diversity of the tree species in the park green belt was P. massoniana > C. deodara > S. babylonica. Differences in EMF community diversity was observed among the different greening tree species in the UGSHs. UGSHs with different disturbance gradients had a significant impact on the EMF diversity of the same greening tree species. These results can be used as a scientific reference for optimizing the design and scientific management of UGSHs.

Abstract Dermatophagoides pteronyssinus (Der p) subcutaneous immunotherapy (SCIT) has demonstrated efficacy in clinical trials of childhood allergic rhinitis (AR). Currently, there is a lack of some generally accepted biomarkers that may predict the clinical response to SCIT to eventually achieve personalized therapy. In this study, 28 children with AR received Der p SCIT for 26–30 months at baseline, and four efficacy endpoints, serum interleukin (IL)-5, periostin, Der p-specific IgE (sIgE), and Der p sIgG4, were measured by ELSIA. Clinical symptoms and characteristics were assessed by questionnaires, and the associations among periostin, Der p 2 sIgE and clinical efficacy were analyzed. The results showed that SCIT demonstrated a significant reduction in Der p 1 sIgE (P

Abstract Deep understanding of sugar metabolite-protein interactions should provide implications on sugar metabolic reprogramming in human physiopathology. Although tremendous efforts have been made for determining individual event, global profiling of such interactome remains challenging. Here we describe thermal proteome profiling of glycolytic metabolite fructose-1,6-bisphosphate (FBP)-interacting proteins. Our results reveal a chemical signaling role of FBP which acts as a phosphate donor to activate phosphoglycerate mutase 1 (PGAM1) and contribute an intrapathway feedback for glycolysis and cell proliferation. At molecular level, FBP donates either C1-O-phosphate or C6-O-phosphate to the catalytic histidine of PGAM1 to form 3-phosphate histidine (3-pHis) modification. Importantly, structure-activity relationship studies facilitate the discovery of PGAM1 orthostatic inhibitors which can potentially restrain cancer cell proliferation. Collectively we have profiled a spectrum of FBP interactome, and discovered a unique covalent signaling function of FBP that supports Warburg effect via histidine phosphorylation which inspires the development of pharmacological tools targeting sugar metabolism.

Abstract Background The purpose of the study was to evaluate renal quality and predict posttransplant graft function using ex vivo sound touch elastography (STE). Methods In this prospective study, 106 donor kidneys underwent ex vivo STE examination and biopsy from March 2022 to August 2023. The mean stiffness of the superficial cortex (STEsc), deep cortex (STEdc), and medulla (STEme) was obtained and synthesized into one index (STE) through the factor analysis method. Additionally, 100 recipients were followed up for 6 months. A random forest algorithm was employed to explore significant predictive factors associated with the Remuzzi score and allograft function. The performance of parameters was evaluated by using the area under the receiver operating characteristic curve (AUC). Results STE had AUC values of 0.803 for diagnosing low Remuzzi and 0.943 for diagnosing high Remuzzi. Meanwhile, STE had an AUC of 0.723 for diagnosing moderate to severe ATI. Random forest algorithm identified STE and Remuzzi score as significant predictors for 6-month renal function. The AUC for STE in predicting postoperative allograft function was 0.717, which was comparable with that of the Remuzzi score (AUC = 0.756). Nevertheless, the specificity of STE was significantly higher than that of Remuzzi (0.913 vs 0.652, p

Abstract In recent years, people have paid increasing attention to smart agriculture. Its core technology is to combine information technology such as computer vision with agricultural production. In agricultural production, the occurrence of pests and diseases can seriously affect agricultural production. Therefore, in agricultural production, the diagnosis and identification of agricultural pests and diseases is the key to improve crop yield. Traditional machine vision methods often rely on feature extraction and classifier design, lack of strong learning and generalization ability, and can not effectively control crop diseases and pests in a timely manner. In order to solve this problem, this paper designs an agricultural pest recognition system based on machine vision algorithm of fuzzy recognition theory, and applies it to agricultural pest recognition. Compared with the traditional machine vision method, this method has obvious advantages, and can effectively improve the monitoring and early warning ability of crop diseases and pests. The experimental results show that the highest recognition rate of the machine vision optimization algorithm based on fuzzy recognition theory is 98.06%, and the lowest recognition error rate is 5.83%. It can be seen that the machine vision recognition algorithm based on fuzzy recognition theory has good recognition effect and can be used in agricultural pest recognition system to help farmers carry out agricultural production and reduce economic losses caused by diseases and pests.

Androgen‐regulated DNA damage response (DDR) is one of the essential mechanisms in prostate cancer (PCa), a hormone‐sensitive disease. The heterogeneous nuclear ribonucleoprotein K (hnRNPK)‐homology splicing regulatory protein known as far upstream element‐binding protein 2 (KHSRP) is an RNA‐binding protein that can attach to AU‐rich elements in the 3′ untranslated region (3′‐UTR) of messenger RNAs (mRNAs) to mediate mRNA decay and emerges as a critical regulator in the DDR to preserve genome integrity. Nevertheless, how KHSRP responds to androgen‐regulated DDR in PCa development remains unclear. This study found that androgen can significantly induce acetylation of KHSRP, which intrinsically drives tumor growth in xenografted mice. Moreover, enhanced KHSRP acetylation upon androgen stimuli impedes KHSRP‐regulated DDR gene expression, as seen by analyzing RNA sequencing (RNA‐seq) and Gene Set Enrichment Analysis (GSEA) datasets. Additionally, NAD‐dependent protein deacetylase sirtuin‐7 (SIRT7) is a promising deacetylase of KHSRP, and androgen stimuli impairs its interaction with KHSRP to sustain the increased KHSRP acetylation level in PCa. We first report the acetylation of KHSRP induced by androgen, which interrupts the KHSRP‐regulated mRNA decay of the DDR‐related genes to promote the tumorigenesis of PCa. This study provides insight into KHSRP biology and potential therapeutic strategies for PCa treatment, particularly that of castration‐resistant PCa.

Abstract Some cases of chronic rhinosinusitis (CRS) require surgical treatment and postoperative nasal packing, but bleeding and adhesion are common complications after nasal surgery. Biodegradable drug-loaded implants hold great therapeutic options for the treatment of CRS, but little data are available regarding the safety and efficacy of a novel drug-loaded haemostatic sponge (DLHS) in the sinus. The aim of this study was to investigate the safety and efficacy of DLHS in the sinus. We conducted a prospective, randomized, controlled, double-blind clinical trial. In this clinical trial, 49 patients were enrolled and randomly divided into 2 groups: group A (n = 25) had the DLHS containing 1 mg budesonide and 0.67 mg sodium hyaluronate placed into the sinus, and group B (n = 24) had the Nasopore placed after ESS. Endoscopic follow-up was performed for 12 weeks, and the findings were classified using the discharge, inflammation, polyps/oedema (DIP) endoscopic appearance scores. All patients completed questionnaires to evaluate their sinonasal symptoms by using the sinonasal outcome test-22 (SNOT-22) Chinese version and visual analogue scale (VAS). Serum cortisol concentration in group A was measured prior to surgery and at days 1, 3, 7, and 14 after nasal surgery. Comparing group A and group B, at 2 weeks, no significant differences were observed in either objective or subjective parameters. The mean value of VAS for rhinorrhoea and DIP for oedema and the mean value of nasal adhesion were significantly lower in Group A than in Group B at 6 and 12 weeks, but a significant difference did not occur in SNOT-22 and VAS for dysosmia between the two groups at 6 and 12 weeks. The mean serum cortisol concentrations in group A at the follow-up were within normal limits without remarkable fluctuations. This study demonstrates the safety and efficacy of a novel biodegradable DLHS with the possibility of being used in CRS patients, and this sponge may reduce inflammation and minimize adhesions via controlled local drug delivery without measurable systemic exposure.

Abstract As per the regulations of Intergovernmental Panel on Climate Change (IPCC), the country’s carbon emission data hold primacy. Nevertheless, establishing and utilizing a database pose a daunting challenge. This study presents the “Carbon Seer System,” a novel software prototype designed to inform and educate users about the carbon footprint during their production and in daily life. The development process involved a three-stage user interview process, ensuring system’s alignment with user needs and preferences. The system employs machine learning and visual recognition technology, including convolutional neural networks (CNNs), feature pyramid networks, and self-attention mechanisms, enabling users to analyze captured images for carbon emission factors. It automatically identifies the carbon emission factors of industrial products, energy producers, household producers, waste treatment, and transportation. A unique “group detection” method allows for the simultaneous analysis of multiple objects in a single image, enhancing user convenience. Additionally, the software features a carbon footprint tracker and a carbon sink dashboard, providing users with insights into their carbon emissions and the efforts needed for offsetting. The study concludes that the “Carbon Seer System” represents a significant step towards individual enablement at understanding and actively participating in a low-carbon lifestyle.

Nowadays, Internet of Things (IoT) is widely deployed and brings great opportunities to change people's daily life. To realize more effective human-computer interaction in the IoT applications, the Question Answering (QA) systems implanted in the IoT services are supposed to improve the ability to understand natural language. Therefore, the distributed representation of words, which contains more semantic or syntactic information, has been playing a more and more important role in the QA systems. However, learning high-quality distributed word vectors requires lots of storage and computing resources, hence it cannot be deployed on the resource-constrained IoT devices. It is a good choice to outsource the data and computation to the cloud servers. Nevertheless, it could cause privacy risks to directly upload private data to the untrusted cloud. Therefore, realizing the word vector learning process over untrusted cloud servers without privacy leakage is an urgent and challenging task. In this paper, we present a novel efficient word vector learning scheme over encrypted data. We first design a series of arithmetic computation protocols. Then we use two non-colluding cloud servers to implement high-quality word vectors learning over encrypted data. The proposed scheme allows us to perform training word vectors on the remote cloud servers while protecting privacy. Security analysis and experiments over real data sets demonstrate that our scheme is more secure and efficient than existing privacy-preserving word vector learning schemes.

Abstract Hepatocellular carcinoma (HCC) still presents poor prognosis with low overall survival rates and limited therapeutic options available. Recently, attention has been drawn to peptidomic analysis, an emerging field of proteomics for the exploration of new potential peptide drugs for the treatment of various diseases. However, research on the potential function of HCC peptides is lacking. Here, we analyzed the peptide spectrum in HCC tissues using peptidomic techniques and explored the potentially beneficial peptides involved in HCC. Changes in peptide profiles in HCC were examined using liquid chromatography-mass spectrometry (LC–MS/MS). Analyze the physicochemical properties and function of differently expressed peptides using bioinformatics. The effect of candidate functional peptides on HCC cell growth and migration was evaluated using the CCK-8, colony formation, and transwell assays. Transcriptome sequencing analysis and western blot were employed to delve into the mode of action of potential peptide on HCC. Peptidomic analysis of HCC tissue yielded a total of 8683 peptides, of which 452 exhibited up-regulation and 362 showed down-regulation. The peptides that were differentially expressed, according to bioinformatic analysis, were closely linked to carbon metabolism and the mitochondrial inner membrane. The peptide functional validation identified a novel peptide, PDLC (peptide derived from liver cancer), which was found to dramatically boost HCC cell proliferation through the Ras/Raf/MEK/ERK signaling cascade. Our research defined the peptide’s properties and pattern of expression in HCC and identified a novel peptide, PDLC, with a function in encouraging HCC progression, offering an entirely new potential therapeutic target the disease.

Abstract The Montreal Protocol has been successful in safeguarding the ozone layer and curbing climate change. However, accurately estimating and reducing the time-lagged emissions of ozone-depleting substances or their substitutes, such as produced but not-yet-emitted fluorocarbon banks, remains a significant challenge. Here, we use a dynamic material flow analysis model to characterize the global stocks and flows of two fluorocarbon categories, hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs), from 1986 to 2060. We assess emission pathways, time-lagged emission sizes, and potential abatement measures throughout different life cycle stages while focusing on the role of banked fluorocarbons in global and regional decarbonization efforts in the post-Kigali Amendment era. Although fluorocarbon releases are expected to decline, the cumulative global warming potential (GWP)-weighted emissions of HCFCs and HFCs are significant; these will be 6.4 (±1.2) and 14.8 (±2.5) gigatons CO2-equivalent, respectively, in 2022–2060 in our business-as-usual (BAU) scenario. Scenario analysis demonstrates that implementing currently available best environmental practices in developed economies can reduce cumulative GWP-weighted emissions by up to 45% compared with the BAU scenario.

The ZCuPb15Sn5/1045 bimetallic composites were prepared by the melt-casting composite method. The mechanical and tribological properties of the copper-steel bimetallic composites under different cooling process conditions were studied. The results showed that with the acceleration of the cooling rate, the copper layer of the copper-steel bimetallic composite became harder, the grain became finer, and the distribution of the anti-friction element Pb became more uniform. Underwater cooling conditions, the shear strength increased, and the shear fracture gradually showed the tendency of tough and brittle fracture. The cooling process had a more significant influence on the tribological properties of the material. When the cooling rate was slow, the copper layer of the bimetallic composites had a high friction coefficient and relatively serious adhesive wear and oxidation wear. For the water cooling sample with a very fast cooling rate, the friction coefficient of the copper layer was low and the wear degree was relatively light.

Geotechnical centrifuge tests were conducted to examine the influence of invert voids and surface traffic loads on 1400 mm diameter reinforced concrete pipes buried with a shallow soil cover depth of 700 mm. Void formation beneath the pipe was simulated during centrifuge testing. The test results revealed that before void formation, the surface load directly above the middle of the pipe caused a significant increase in not only the circumferential bending moments but also the longitudinal bending moments, the latter of which was considerable and could not be ignored. Void formation beneath the middle of the pipe led to a reduction in both the circumferential bending moments and longitudinal bending moments at all measuring positions, i.e., crown, springline, and invert. The most significant reduction occurred at the invert, and there was even a reversal in the sign of the invert longitudinal bending moment. A comparison was made between centrifuge tests with erosion voids and surface loads at different horizontal positions, which had a marked influence even when the positions differed by half a pipe length. Joint rotation played an important role in relieving large bending moments of pipe barrels in a jointed pipeline when the void and surface load were located at the joint.

The COVID-19 pandemic has posed severe threats to global sustainable development. However, a comprehensive quantitative assessment of the impacts of COVID-19 on Sustainable Development Goals (SDGs) is still lacking. This research quantified the post-COVID-19 SDG progress from 2020 to 2024 using projected GDP growth and population and machine learning models including support vector machine, random forest, and extreme gradient boosting. The results show that the overall SDG performance declined by 7.7% in 2020 at the global scale, with 12 socioeconomic SDG performance decreasing by 3.0%–22.3% and 4 environmental SDG performance increasing by 1.6%–9.2%. By 2024, the progress of 12 SDGs will lag behind for one to eight years compared to their pre-COVID-19 trajectories, while extra time will be gained for 4 environment-related SDGs. Furthermore, the pandemic will cause more impacts on countries in emerging markets and developing economies than those on advanced economies, and the latter will recover more quickly to be closer to their pre-COVID-19 trajectories by 2024. Post-COVID-19 economic recovery should emphasize in areas that can help decouple economic growth from negative environmental impacts. The results can help government and non-state stakeholders identify critical areas for targeted policy to resume and speed up the progress to achieve SDGs by 2030.

Abstract Understanding the combined effects of risk factors on all-cause mortality is crucial for implementing effective risk stratification and designing targeted interventions, but such combined effects are understudied. We aim to use survival-tree based machine learning models as more flexible nonparametric techniques to examine the combined effects of multiple physiological risk factors on mortality. More specifically, we (1) study the combined effects between multiple physiological factors and all-cause mortality, (2) identify the five most influential factors and visualize their combined influence on all-cause mortality, and (3) compare the mortality cut-offs with the current clinical thresholds. Data from the 1999–2014 NHANES Survey were linked to National Death Index data with follow-up through 2015 for 17,790 adults. We observed that the five most influential factors affecting mortality are the tobacco smoking biomarker cotinine, glomerular filtration rate (GFR), plasma glucose, sex, and white blood cell count. Specifically, high mortality risk is associated with being male, active smoking, low GFR, elevated plasma glucose levels, and high white blood cell count. The identified mortality-based cutoffs for these factors are mostly consistent with relevant studies and current clinical thresholds. This approach enabled us to identify important cutoffs and provide enhanced risk prediction as an important basis to inform clinical practice and develop new strategies for precision medicine.

Background Surgical treatment for hinge failure in mega‐prosthesis continues to be a challenge. This study introduces a new method for treating hinge failure by using a unilateral prosthesis and hinge revision. Case Presentation We here present two patients who underwent mega‐prosthesis reconstruction after resection of osteosarcoma in the distal femur. To address the issue of knee hyperextension after mega‐prosthesis reconstruction, one patient underwent three revision surgeries, two surgeries were performed using the original hinge, and one surgery involved a newly designed hinge. To resolve the problem of dislocation, one patient underwent three revisions, with the first two revisions not involving hinge replacement and the third revision involving a newly designed hinge. Two replacements of unilateral prosthesis and hinge renovations were successful. Conclusions Unilateral prosthesis and newly designed hinge device revision are effective in treating the failure of old‐fashioned mega‐prosthesis hinges.

IntroductionEffective postoperative pain management remains a significant challenge due to the severe side effects of opioids and the limitations of existing analgesic delivery systems. Inflammation plays a critical role in pain exacerbation, highlighting the need for therapies that combine analgesic effects with intrinsic anti-inflammatory properties.MethodsHerein, we develop an intrinsic anti-inflammatory nanomedicine designed to enhance pain management by integrating controlled anesthetic release with inherent anti-inflammatory activity. Our nanoplatform utilizes dendritic mesoporous silica nanoparticles (MSNs) loaded with levobupivacaine and coated with Rg3-based liposomes derived from ginsenoside Rg3, termed LMSN-bupi.ResultsThe MSNs enable sustained and controlled release of the local anesthetic, while the Rg3-liposome coating provides intrinsic anti-inflammatory effects by inhibiting macrophage activation. In animal models, LMSN-bupi demonstrates significantly prolonged analgesic effects and attenuated inflammatory responses compared to traditional liposome-decorated nanoparticles (TMSN-bupi) (n = 5).DiscussionThese findings underscore the potential of intrinsic anti-inflammatory nanomedicines in enhancing pain management, offering a promising strategy to overcome the limitations of current therapies and improve patient outcomes in postoperative care.

IntroductionThe involvement of thyroid hormone in cardiovascular disease remains debated. The aim of our research was to ascertain whether thyroid hormone sensitivity indices are related to carotid plaque (CAP) risk in the general population.MethodsWe recruited 5,360 participants for health examinations to explore the correlation between thyroid hormone sensitivity indices and CAP risk. We then compared baseline characteristics of participants with CAP to those without CAP based on multivariate logistic regression analysis. Additionally, we conducted subgroup analyses stratified by gender and age to further elucidate this relationship.ResultsAmong the 5,360 participants, 1,055 (19.7%) were diagnosed with CAP. After adjusting for various confounding factors, our results showed a positive association between CAP risk and the indices (TFQI, PTFQI, TSHI, and TT4RI). Conversely, the FT3/FT4 ratio showed a negative correlation with CAP risk. Sex-based subgroup analysis revealed a stronger correlation between thyroid hormone sensitivity and CAP in females compared to males. In the age subgroup, the significant association was observed in older individuals (age >60) compared to middle-aged participants (age ≤60).ConclusionOur study suggests a significant correlation between thyroid hormone sensitivity and CAP, particularly in females and participants over the age of 60.

BackgroundColorectal cancer (CRC) is a leading cause of cancer-related deaths globally. The heterogeneity of the tumor microenvironment significantly influences patient prognosis, while the diversity of tumor cells shapes its unique characteristics. A comprehensive analysis of the molecular profile of tumor cells is crucial for identifying novel molecular targets for drug sensitivity analysis and for uncovering the pathophysiological mechanisms underlying CRC.MethodsWe utilized single-cell RNA sequencing technology to analyze 13 tissue samples from 4 CRC patients, identifying key cell types within the tumor microenvironment. Intercellular communication was assessed using CellChat, and a risk score model was developed based on eight prognostic genes to enhance patient stratification for immunotherapeutic approaches. Additionally, in vitro experiments were performed on DLX2, a gene strongly associated with poor prognosis, to validate its potential role as a therapeutic target in CRC progression.ResultsEight major cell types were identified across the tissue samples. Within the tumor cell population, seven distinct subtypes were recognized, with the C0 FXYD5+ tumor cells subtype being significantly linked to cancer progression and poor prognosis. CellChat analysis indicated extensive communication among tumor cells, fibroblasts, and immune cells, underscoring the complexity of the tumor microenvironment. The risk score model demonstrated high accuracy in predicting 1-, 3-, and 5-year survival rates in CRC patients. Enrichment analysis revealed that the C0 FXYD5+ tumor cell subtype exhibited increased energy metabolism, protein synthesis, and oxidative phosphorylation, contributing to its aggressive behavior. In vitro experiments confirmed DLX2 as a critical gene associated with poor prognosis, suggesting its viability as a target for improving drug sensitivity.ConclusionIn summary, this study advances our understanding of CRC progression by identifying critical tumor subtypes, molecular pathways, and prognostic markers that can inform innovative strategies for predicting and enhancing drug sensitivity. These findings hold promise for optimizing immunotherapeutic approaches and developing new targeted therapies, ultimately aiming to improve patient outcomes in CRC.

ABSTRACTThis experiment is to investigate whether interspecies differences exist in the effects of leucine (Leu) on digestive enzyme secretion in pancreatic tissues through in vitro. Five healthy Simmental cattle and Duroc × Landrace × Yorkshire growing-finishing pigs were selected, and pancreatic tissues were taken for culture after slaughter. Leu levels of 0, 2.62, 5.24, 10.48 mg/mL. Leu levels of 0, 5.24 mg/mL were selected to determine the expression of mRNA and proteins in the signaling pathways. The results showed that Leu increased the activity of digestive enzyme in cattle and pig, and there was an interaction was found on trypsin and chymotrypsin (P

AbstractAim This article introduces the giant magneto-impedance-based MEG detection technique to facilitate and inspire researchers wishing to engage in related studies.Methods We take non-invasive brain-computer interface (BCI) as the application background, and firstly analyze the advantages of magnetoencephalography (MEG) over electroencephalography (EEG) in terms of practicality, temporal and spatial resolution, and data acquisition. Then the development status of the major MEG detection techniques are overviewed. In addition, the circuit structure and research status of GMI sensor are outlined. Finally, the future development trends and challenges of the MEG-based BCI technology and the MEG detection technique based on GMI sensor are analyzed and summarized.Conclusion Detecting MEG signals in an unshielded environment is a worldwide challenge. The MEG detection technique based on the GMI effect has a promising application in the field of BCI, so it is significant to conduct the investigation of this technique.

Graphic design, as a product of the burgeoning new media era, has seen its users’ requirements for images continuously evolve. However, external factors such as light and noise often cause graphic design images to become distorted during acquisition. To enhance the definition of these images, this paper introduces a novel image enhancement model based on visual features. Initially, a histogram equalization (HE) algorithm is applied to enhance the graphic design images. Subsequently, image feature extraction is performed using a dual-flow network comprising convolutional neural network (CNN) and Transformer architectures. The CNN employs a residual dense block (RDB) to embed spatial local structure information with varying receptive fields. An improved attention mechanism module, attention feature fusion (AFF), is then introduced to integrate the image features extracted from the dual-flow network. Finally, through image perception quality guided adversarial learning, the model adjusts the initial enhanced image’s color and recovers more details. Experimental results demonstrate that the proposed algorithm model achieves enhancement effects exceeding 90% on two large image datasets, which represents a 5%–10% improvement over other models. Furthermore, the algorithm exhibits superior performance in terms of peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) image quality evaluation metrics. Our findings indicate that the fusion model significantly enhances image quality, thereby advancing the field of graphic design and showcasing its potential in cultural and creative product design.

BackgroundCoronary heart disease (CHD) is one of the leading causes of mortality. The current study aims to assess the association between C-reactive protein-triglyceride glucose index (CTI) and the risk of prevalent CHD and to evaluate the usefulness of CTI to refine the identification of prevalent CHD.Methods19,451 subjects from the National Health and Nutrition Examination Survey 1999–2010 were enrolled. CHD was ascertained according to the questionnaire.ResultsThe prevalent of CHD was 6.23%. After adjusting for conventional cardiovascular risk factors, each SD increase of CTI could cast a 1.357 times risk of CHD. In quartile analysis, the top quartile had a 1.807 times risk of CHD than the bottom quartile. Smooth curving fitting displayed that the association was linear in the entire range of CTI. Subgroup analysis revealed that the association was robust among several common subpopulations but stronger in subjects aged

BackgroundTumor resection near the proximal end of the femur and revision surgery of the distal femoral prosthesis may result in a very short bone segment remaining at the proximal end of the femur, known as ultrashort residual proximal femur (URPF). In this study, we propose a triangular fixation stem (TFS) prosthesis to improve the fixation of URPF. The aim of this research is to investigate the biomechanical properties of the TFS prosthesis and compare it with the conventional stem (CS) prosthesis through in vitro biomechanical experiments, providing preliminary biomechanical evidence for prosthetic fixation of URPF.MethodsA biomechanical study was conducted using Sawbones to explore initial stability. Twelve Sawbones were used to create a bone defect model, and prostheses were designed and fabricated to emulate TFS fixation and CS fixation structures. Axial compression and horizontal torsion experiments were performed on the fixed models using a mechanical testing machine, recording maximum displacement, maximum torque, and femoral strain conditions.ResultsUnder an axial compressive load of 2800 N, the overall displacement of the TFS group was 3.33 ± 0.58 mm, which was significantly smaller than that of the CS group (4.03 ± 0.32 mm, P = 0.029). The femoral samples of the TFS group demonstrated that the strain value alterations at the medial points 2, 3, 5, 6 and the lateral point 10 were conspicuously smaller than those of the conventional stem group (P < 0.05). Under torsional loads at levels of 1°, 3°, and 5°, the torques of the TFS group were 3.86 ± 0.69 Nm, 3.90 ± 1.26 Nm, and 4.39 ± 1.67 Nm respectively, all of which were significantly greater than those of the CS group (1.82 ± 0.82 Nm, P < 0.001; 2.05 ± 0.89 Nm, P = 0.016; 1.96 ± 0.50 Nm, P = 0.015 respectively).ConclusionThe TFS prosthesis improves fixation strength and reduces strain on the femur’s proximal surface. Compared to CS fixation, it offers better resistance to compression and rotation, as well as improved initial stability.

IntroductionAcupoint Catgut Embedding (ACE) is an extended and developed form of traditional acupuncture that serves as a composite stimulation therapy for various diseases. However, its local stimulation effects on acupoints remain unclear. Acupuncture can activate mechanically sensitive calcium ion channels, TRPV2 and TRPV4, located on various cell membranes, promoting Ca2+ influx in acupoint tissues to exert effects. Whether ACE can form mechanical physical stimulation to regulate these channels and the related linkage effect requires validation.MethodsThis study investigates the influence of TRPV2 and TRPV4 ion channels on the local stimulation effects of ACE by embedding PGLA suture at the Zusanli (ST36) acupoint in rats and using TRPV2 and TRPV4 inhibitors. Flow cytometry, immunofluorescence, Western blot, and Real-time quantitative PCR were employed to detect intracellular Ca2+ fluorescence intensity, the expression of macrophage (Mac) CD68 and mast cell (MC) tryptase, as well as the protein and mRNA expression of TRPV2 and TRPV4 in acupoint tissues after PGLA embedding.ResultsThe results indicate that ACE using PGLA suture significantly increases the mRNA and protein expression of TRPV2 and TRPV4, Ca2+ fluorescence intensity, and the expression of Mac CD68 and MC tryptase in acupoint tissues, with these effects diminishing over time. The increasing trends are reduced after using inhibitors, particularly when both inhibitors are used simultaneously. Furthermore, correlation analysis shows that embedding PGLA suture at the ST36 acupoint regulates Mac and MC functions through Ca2+ signaling involving not only TRPV2 and TRPV4 but multiple pathways.DiscussionThese results suggest that embedding PGLA suture at the ST36 acupoint generates mechanical physical stimulation and regulates TRPV2 and TRPV4 ion channels, which couple with Ca2+ signaling to form a linkage effect that gradually weakens over time. This provides new reference data for further studies on the stimulation effects and clinical promotion of ACE.

Abstract Background Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet β cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed. Methods db/db, high-fat diet (HFD)-fed, and global pannexin 1 (PANX1) knockout mice, as well as liver sections of individuals, were used in this study. Adenoviruses and adeno-associated viruses were utilized for in vivo gene overexpression or inhibition. To evaluate the metabolic status in mice, oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT), insulin tolerance test (ITT), and magnetic resonance imaging (MRI) were conducted. Protein–protein interactions were determined by coimmunoprecipitation with mass spectrometry (MS) assays. Results In livers of individuals and mice with steatosis, the expression of ATP-permeable channel PANX1 was increased (P

Background Revision of tumor‐type prosthetic fractures is very challenging in clinical work. Traditional repair methods may not be able to meet the needs of complex cases or cause greater bone damage. Therefore, more effective and reliable solutions need to be found. Case Presentation This study presents a novel revision technique for managing fractures of tumor‐type total elbow prostheses. A 57‐year‐old female patient was diagnosed with a left distal humeral bone tumor accompanied by pathological fracture and underwent customized tumor‐type total elbow prosthesis arthroplasty. After 5 years, she experienced pain and encountered difficulty in flexing the left elbow while lifting heavy objects. The X‐ray examination revealed a fracture of the distal humeral prosthesis. As a response, the elbow joint was initially explored, and the damaged component of the prosthesis was extracted. Subsequently, we utilized 3D printing technology to design a split‐piece sleeve prosthesis and effectively restored the fractured left distal humerus implant. During the 2‐year follow‐up, The X‐ray demonstrated satisfactory positioning of the prosthesis, which remained securely affixed without any indications of loosening. The Mayo Elbow Performance Score (MEPS) reached 80 points, the Musculoskeletal Tumor Society (MSTS) attained a score of 28 points, and the range of motion of the elbow was measured between 25° and 110°, revealing favorable functional outcomes. Conclusion The utilization of a 3D printed split‐piece sleeve prosthesis presents a viable clinical treatment strategy for addressing fractures in tumor‐type elbow prostheses.

Abstract Polyamines, such as putrescine, spermidine, and spermine, are crucial for plant defense against both abiotic and biotic stresses. Putrescine is also known as a significant inducer of deoxynivalenol (DON) production in Fusarium graminearum, the primary causal agent of Fusarium head blight (FHB). However, the impact of other polyamines on DON production and whether modifying polyamine biosynthesis could improve wheat resistance to FHB are currently unknown. In this study, we demonstrate that key precursor components of putrescine synthesis, including arginine, ornithine, and agmatine, can induce DON production, albeit to a lesser extent than putrescine in trichothecene biosynthesis-inducing (TBI) culture under the same total nitrogen conditions. Intriguingly, spermidine and spermine, downstream products of putrescine in the polyamine biosynthesis pathway, do not induce DON production under the same conditions. Additionally, externally applying either spermidine or spermine to wheat heads significantly reduces the diseased spikelet number caused by F. graminearum. Furthermore, our results show that overexpression of the wheat spermidine synthase (SPDS) gene TaSPDS-7D1 significantly enhances the spermidine content and wheat resistance to FHB. In addition, the TaSPDS-7D1-overexpressing line OE3 exhibited a 1000-grain weight and plant height increase compared to the wild type. Our findings reveal that overexpression of the spermidine synthase gene can enhance wheat resistance to FHB without compromising wheat yield.

Abstract The indication of information in materials is widely used in our daily life, and optical encoding materials are ideal for information loading due to their easily readable nature and adjustable optical properties. However, most of them could only indicate one type of information, either changing or unchanging due to the mutual interference. Inspired by firefly, we present a non-interfering bipolar information indication system capable of indicating both changing and unchanging information. A photochemical afterglow material is incorporated into the photonic crystal matrix through a high-throughput technique called shear-induced ordering technique, which can efficiently produce large-area photonic crystal films. The indication of changing and unchanging information is enabled by two different utilizations of white light by the afterglow material and photonic crystals, respectively, which overcome the limitations of mutual interference. As a proof of concept, this system is used to indicate the changing photodegradation level of mecobalamin (a photosensitive medicine) and unchanging intrinsic drug information with anti-counterfeiting functionality, which is a promising alternative to instantly ascertain the efficacy of medicine at home where conventional assays are impractical.

Abstract Background As a recognized win–win-win approach to international debt relief, Debt-to-Health(D2H)has successfully translated debt repayments into investments in health-related projects. Although D2H has experienced modifications and periodic suspension, it has been playing an increasingly important role in resource mobilization in public health, particularly for low-and middle-income countries deep in debt. Main text D2H, as a practical health financing instrument, is not fully evidenced and gauged by academic literature though. We employed a five-step scoping review methodology. After posing questions, we conducted comprehensive literature searches across three databases and one official website to identify relevant studies.We also supplemented our research with expert interviews. Through this review and interviews, we were able to define the concept and structure of D2H, identify stakeholders, and assess its current shortcomings. Finally, we proposed relevant countermeasures and suggestions. Conclusion This paper examines the D2H project's implementation structure and influencing variables, as well as the current research plan's limitations, with a focus on the role health funding institutions have played during the project's whole life. Simultaneously, it examines the interdependencies between debtor nations, creditor nations, and health financing establishments, establishing the groundwork for augmenting and revamping D2H within the ever-changing worldwide context of health development assistance.

Abstract Background To analyse the causal associations of different physical measures with osteoarthritis knee (KOA). Methods Exposure factors (weight, body mass index (BMI), body fat percentage, waist circumference, hip circumference, waist–hip ratio (WHR), and basal metabolic rate (BMR)), and outcome factor KOA were analyzed by inverse-variance weighted (IVW) method, along with heterogeneity test, sensitivity and pleiotropy analyses. Meta-analysis was used to combine the effect values of IVW methods in different data sources. Results Weight, BMI, body fat percentage, waist circumference, hip circumference and BMR analyses showed causal association with increased KOA risk, while WHR analysis indicated a reduction of the incidence of KOA. P-value for all the results was less than 0.05 and F-value large than 20. All results were negative for heterogeneity tests and sensitivity analyses, and there was pleiotropy in weight and BMR. Meta-analysis results showed that the results of Odds Ratios (95% Confidence Intervals) for Weight (1.43(1.35–1.51)), BMI (1.40(1.10–1.78)), body fat percentage (1.56(1.44–1.68)), waist circumference (1.40(1.10–1.78)), hip circumference (1.37(1.30–1.44)), WHR (0.86(0.71–1.04)) and BMR (1.36(1.27–1.46) were consistent with the ones by Mendelian randomization analyses. Conclusions Body fat percentage may be a better indicator of KOA than BMI. In addition, weight and BMR may have a causal effect in KOA, but WHR does not have a causal relationship. BMI, body fat percentage, waist circumference, and hip circumference has a causal effect on KOA.

BackgroundAs the population ages, there has been a growing focus on the decline in fertility. Research has identified age and fertility history as the primary influencing factors. Nevertheless, there is a deficiency in fundamental data regarding the fertility status among different industries. ObjectiveTo investigate the fertility status and influencing factors among female workers aged 22-35 years in different industries. MethodsFrom July 2020 to February 2021, a cross-sectional survey was conducted using a staged sampling approach. This survey specifically targeted 22-35-year-old married female workers with a history of pregnancy in industries such as education, healthcare, finance, and telecommunications, totaling 22903 participants. The survey encompassed industry, demographic characteristics, pregnancy history, time to pregnancy (TTP), and other influencing factors. The influencing factors of decline in fertility were identified by chi-square test and Cox proportional hazards regression. Subsequent industry-specific Cox proportional hazards regression models were used to compared fertility decline patterns across a spectrum of industries after selected influencing factors were adjusted. ResultsAmong the 22903 respondents, 19194 valid questionnaires were collected, with a valid recovery rate of 83.8%. The cumulative pregnancy rates (CRP) of 1-6 months and 1-12 months for the 22-35-year-old female workers were 67.23% and 91.33% respectively. The multivariate analysis showed that region, age, education level, personal annual income, housework time, coping style, gravidity, parity, and spontaneous abortion were influencing factors of fertility decline (P

Background: Gallbladder cancer (GBC) is one of the most lethal malignancies worldwide with an extremely poor prognosis. Previous studies have suggested that tripartite motif containing 47 (TRIM47) is involved in the progression of numerous cancers. However, the molecular mechanism and function of TRIM47 in GBC remain unclear. Methods: The clinical significance of TRIM47 was evaluated using immunohistochemistry. Functional assays were performed in vitro and in vivo to determine the role of TRIM47 in GBC. Mass spectrometric analysis, western blotting, and immunoprecipitation assays were performed to investigate the molecular mechanisms involved. Results: In this study, TRIM47 was upregulated in GBC tissues and associated with shorter overall survival rates and TRIM47 was involved in GBC cell proliferation, migration, and apoptosis. Mechanistically, TRIM47 interacts with PARP1 and mediates the K63-linked polyubiquitination of PARP1, thereby stabilizing its expression. Furthermore, TRIM47 activated the AKT signaling pathway via PARP1. Conclusion: The present study revealed that TRIM47 contributes to the progression of GBC and is therefore an important biomarker for predicting the prognosis of GBC and for therapeutic intervention.

Abstract Crystallization speed of phase change material is one of the main obstacles for the application of phase change memory (PCM) as storage class memory in computing systems, which requires the combination of nonvolatility with ultra‐fast operation speed in nanoseconds. Here, we propose a novel approach to speed up crystallization process of the only commercial phase change chalcogenide Ge2Sb2Te5 (GST). By employing TiO2 as the dielectric layer in phase change device, operation speed of 650 ps has been achieved, which is the fastest among existing representative PCM, and is comparable to the programing speed of commercial dynamic random access memory (DRAM). Because of its octahedral atomic configuration, TiO2 can provide nucleation interfaces for GST, thus facilitating the crystal growth at the determinate interface area. Ti–O–Ti–O four‐fold rings on the (110) plane of tetragonal TiO2 is critical for the fast‐atomic rearrangement in the amorphous matrix of GST that enables ultra‐fast operation speed. The significant improvement of operation speed in PCM through incorporating standard dielectric material TiO2 in DRAM paves the way for the application of phase change memory in high performance cache‐type data storage.

Residential buildings have a significant potential for energy conservation. The building energy consumption process is a complex system influenced by several factors at climate, building system, and occupant levels. This study introduces a novel model based on a multi-agent system to systematically integrate these multiple influencing factors, simulate their interactions, and estimate the resultant cooling and heating energy with dynamic variations over years considered. The automatic dynamic energy simulation was conducted over 30 years considering four temporal parameters (i.e., outdoor temperature, heat transfer coefficient of the building envelope, household type, and behavior pattern of occupants). A case building was used to validate the model, and the dynamic annual results were quite different from the static ones. The dynamic cumulative cooling energy consumption during 31 years was 0.69 % lower than the static one, whereas dynamic cumulative heating energy was 7.53 % higher compared with static energy. It highlighted the importance of considering dynamic multi-agent interactions. Besides, the roles of multiple energy influencing factors and dynamic parameters were compared and discussed. This study provides critical insights into improving building energy performance and offers a rapid and automatic approach for dynamic energy simulation.

Denosumab has recently become an important part of the treatment regime for spinal giant cell tumors of the bone (GCTB). Its use has significantly reduced the risk of surgery and postoperative complications in patients with spinal GCTB. However, the use of denosumab has not yet been optimized to reap the maximum benefits. Here, we have reported the case of a patient who was treated with denosumab in combination with excision and scraping for GCTB of the T10 vertebrae, which achieved good tumor control and no recurrence at the 2-year postoperative follow-up. We have also reviewed the case in the light of relevant literature as well as presented our ideas and recommendations for the optimal use of denosumab.

Over the last three decades, ocean color satellites have recorded continuous change in phytoplankton concentration, and in doing so, the satellites have helped marine remote sensing to become an emerging discipline. However, ocean color satellite has provided the state of global phytoplankton only around midday whereas phytoplankton have significant diurnal variation characteristics over an entire day-night cycle, which would lead to large estimation uncertainty in downstream products. A large global field observations show that the diurnal variation curves can be constructed as the sum of an exponential and a polynomial function. After correction with our diurnal variation curves, the intermission difference between MODISA and MODIST phytoplankton product could be decreased from 7.57% to 6%, which is critical to monitor the long-term changing trend with multi-mission data. When the satellite-recorded chlorophyll-a concentration is simply equal to a daily average value, it results in overestimating uncertainties of 16% and 54% for the northern and southern hemispheric oceans, respectively. Moreover, as a typical example of downstream product of the chlorophyll-a, the coverage of oligotrophic waters can oscillate 76% from day to night simulated from satellite images with our diurnal variation curves, further confirming the importance of global synchronous observation. The geostationary satellite might be an efficient regional tool for diurnal observation, but it must account for its limitations under the weak light conditions of early morning and late afternoon. In the real world, the effects of diurnal variations in ocean properties reach far beyond chlorophyll-a in the global oceans. We anticipate these quantitatively findings to be a starting point for quantitatively re-examining the proper application of ocean color products in scientific communication.

The peel stripe margin pattern is one of the most important quality traits of watermelon. In this study, two contrasted watermelon lines [slb line (P1) with a clear peel stripe margin pattern and GWAS-38 line (P2) with a blurred peel stripe margin pattern] were crossed, and biparental F2 mapping populations were developed. Genetic segregation analysis revealed that a single recessive gene is modulating the main-effect genetic locus (Clcsm) of the clear stripe margin pattern of peel. Bulked segregant analysis-based sequencing (BSA-Seq) and fine genetic mapping exposed the delimited Clcsm locus to a 19.686-kb interval on chromosome 6, and the Cla97C06G126680 gene encoding the MYB transcription factor family was identified. The gene mutation analysis showed that two non-synonymous single-nucleotide polymorphism (nsSNP) sites [Chr6:28438793 (A-T) and Chr6:28438845 (A-C)] contribute to the clear peel stripe margin pattern, and quantitative real-time polymerase chain reaction (qRT-PCR) also showed a higher expression trend in the slb line than in the GWAS-38 line. Further, comparative transcriptomic analysis identified major differentially expressed genes (DEGs) in three developmental periods [4, 12, and 20 days after pollination (DAP)] of both parental lines. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses indicated highly enriched DEGs involved in metabolic processes and catalytic activity. A total of 44 transcription factor families and candidate genes belonging to the ARR-B transcription factor family are believed to regulate the clear stripe margin trait of watermelon peel. The gene structure, sequence polymorphism, and expression trends depicted significant differences in the peel stripe margin pattern of both parental lines. The ClMYB36 gene showed a higher expression trend for regulating the clear peel stripe margin of the slb line, and the ClAPRR5 gene depicted a higher expression for modulating the blurred peel stripe margin in the GWAS-38 line. Overall, our fine genetic mapping and transcriptomic analysis revealed candidate genes differentiating the clear and blurred peel stripe patterns of watermelon fruit.

The interactions between human serum albumin (HSA) and the hemostatic components of the Chinese medicine Sanguisorbae Radix (SR), specifically phenolic acid compounds such as caffeic acid (CA), ferulic acid (FA) and their 1:1 mixture (1:1) were studied to investigate the molecular mechanism underlying the hemostatic effect of SR. Network pharmacology combined with the experimental and computational data revealed that HSA is one of the hemostatic targets to SR phenolic acids. SDS-PAGE and multi-spectroscopy demonstrated that the phenolic acids bind to the Sudlow site I on HSA, altering its structure and influencing its migration velocity. There is an observed synergistic effect upon the mixture of CA and FA. Quantum chemistry, molecular docking, and molecular dynamics simulations indicate that the binding of phenolic acids to HSA is stable, and variations in binding efficiency are associated with the hydrophobicity of the substituent at the C3 position of the side chain, and also, the key amino acids and functional groups for hemostasis of SR were identified, along with the active sites that contribute to the synergistic enhancement by phenolic acids.

ObjectivePrevious observational studies have suggested an association between gut microbiota and diabetic neuropathy (DN). However, confounding factors and reverse causality make the causal relationship between gut microbiota and DN uncertain. We aimed to investigate the interactive causal relationships between the abundance of gut microbiota and DN.MethodsWe conducted a Mendelian randomization (MR) analysis to examine the causal relationship between gut microbiota and DN. Genomic data on gut microbiota at the genus level were obtained from the MiBioGen Consortium, including 18,340 individuals of European descent. Data on diabetic polyneuropathy (DPN) were obtained from the FinnGen Consortium, which included 1,048 cases and 374,434 controls, while data on diabetic autonomic neuropathy (DAN) were also obtained from the FinnGen Consortium, including 111 cases and 374,434 controls. Causal effects were primarily estimated using inverse variance weighted (IVW) analysis, supplemented with four validation methods, and additional sensitivity analyses to assess the pleiotropy, heterogeneity, and robustness of instrumental variables.ResultsThe IVW analysis indicated that Prevotella 9 had a protective effect on DPN (OR = 0.715, 95% CI: 0.521-0.982, P = 0.038), and Bacteroides also showed a protective effect (OR = 0.602, 95% CI: 0.364-0.996, P = 0.048). On the other hand, Ruminococcus 2 had a promoting effect on DPN (OR = 1.449, 95% CI: 1.008-2.083, P = 0.045). Blautia (OR = 0.161, 95% CI: 0.035-0.733, P = 0.018), Clostridium innocuum group (OR = 3.033, 95% CI: 1.379-6.672, P = 0.006), and Howardella (OR = 2.595, 95% CI: 1.074-6.269, P = 0.034) were causally associated with DAN in the IVW analysis, with no evidence of heterogeneity or pleiotropy. Sensitivity analyses showed no significant pleiotropy or heterogeneity.ConclusionOur study identified a causal relationship between gut microbiota and the increased or decreased risk of diabetic neuropathy. These findings underscore the importance of adopting a comprehensive approach that combines gut microbiota modulation with other therapeutic interventions in the management of diabetic neuropathy.

Summary: Population-normalized indicators (e.g., GDP per capita), under the assumption of the indicators scaling linearly with population, are ubiquitously used in national development performance comparison. This assumption, however, is not valid because it may ignore agglomeration effect resulting from nonlinear interactions in socioeconomic systems. Here, we present extensive empirical evidence showing the sub-linear scaling rather than the presumed linear scaling between population and multiple indicators of national development performance. We then develop a theoretical framework based on the scaling rule observed in cities to explore the origin of scaling in countries. Finally, we demonstrate that urbanization plays a pivotal role in transforming national development from limited sub-linear growth to unlimited super-linear growth. This underscores the significance of urbanization in achieving sustained growth and elevating human living standards at the national level. Our findings have the potential to inform policies aimed at promoting equitable inter-country comparison and achieving sustainable development in countries.

Primary intraosseous malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive neoplasms originating from peripheral nerves. Typically manifesting as soft tissue masses accompanied by pain or functional impairment, these tumors pose significant challenges in management. Surgical intervention remains the cornerstone of treatment for patients with MPNST lacking distant metastasis, with generally modest success rates. In cases of recurrence and metastasis, the pursuit of effective systemic therapies has been a focus of clinical investigation. Herein, we present a case study involving an elderly female patient with refractory MPNST. In light of surgical limitations, a multimodal therapeutic approach combining chemotherapy, denosumab, and subsequent administration of anlotinib was pursued following collaborative consultation. This regimen yielded noteworthy clinical benefits, exemplifying a promising avenue in the management of challenging MPNST cases.

Filamentous cell growth is a vital property of fungal pathogens. The mechanisms of filamentation in the emerging multidrug-resistant fungal pathogen Candida auris are poorly understood. Here, we show that exposure of C. auris to glycerol triggers a rod-like filamentation-competent (RL-FC) phenotype, which forms elongated filamentous cells after a prolonged culture period. Whole-genome sequencing analysis reveals that all RL-FC isolates harbor a mutation in the C2H2 zinc finger transcription factor-encoding gene GFC1 (Gfc1 variants). Deletion of GFC1 leads to an RL-FC phenotype similar to that observed in Gfc1 variants. We further demonstrate that GFC1 mutation causes enhanced fatty acid β-oxidation metabolism and thereby promotes RL-FC/filamentous growth. This regulation is achieved through a Multiple Carbon source Utilizer (Mcu1)-dependent mechanism. Interestingly, both the evolved RL-FC isolates and the gfc1Δ mutant exhibit an enhanced ability to colonize the skin. Our results reveal that glycerol-mediated GFC1 mutations are beneficial during C. auris skin colonization and infection.