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Yiqiao Xie,1,* Zhiquan Zhuang,2,* Shu Zhang,1 Zihua Xia,1 De Chen,1 Kaiyan Fan,1 Jialin Ren,1 CuiCui Lin,1 Yanzhong Chen,1 Fan Yang1 1Department of Pharmaceutics, Guangdong Pharmaceutical University, 2Department of Pharmacy, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Purpose: The present study examined the factors affecting the content of impurities of nimodipine (NMP) emulsion and the associated methods of compound protection.Methods: Destructive testing of NMP emulsion and its active pharmaceutical ingredient (API) were conducted, and ultracentrifugation was used to study the content of impurities in two phases. The impurity of NMP was measured under different potential of hydrogen (pH) conditions, antioxidants and pH-adjusting agents.Results: Following destruction, the degradation of NMP notably occurred in the basic environment. The consumption of the pH-adjusting agent NaOH was proportional to the production of impurities since the inorganic base and/or acid promoted the degradation of NMP. The organic antioxidants, notably amino acids with an appropriate length of intermediate chain and electron-donating side group, exhibited improved antioxidant effects compared with inorganic antioxidants. The minimal amount of impurities was produced following addition of 0.04% lysine and 0.06% leucine in the aqueous phase and adjustment of the pH to a range of 7.5–8.0 in the presence of acetic acid solution.Conclusion: NMP was more prone to degradation in an oxidative environment, in an aqueous phase and/or in the presence of inorganic pH-adjusting agents and antioxidants. The appropriate antioxidant and pH-adjusting agent should be selected according to the chemical structure, while destructive testing of the drug is considered to play the optimal protective effect. Keywords: nimodipine emulsion, impurity, destructive testing, ultracentrifugation, antioxida­tion, pH

Hydrogels are promising materials for wound protection, but in wet, or underwater environments, the hydration layer and swelling of hydrogels can seriously reduce adhesion and limit their application. In this study, inspired by the structural characteristics of strong barnacle wet adhesion and combined with solvent exchange, a robust wet adhesive hydrogel (CP-Gel) based on chitosan and 2-phenoxyethyl acrylate was obtained by breaking the hydration layer and resisting swelling. As a result, CP-Gel exhibited strong wet adhesion to various interfaces even underwater, adapted to joint movement and skin twisting, resisted sustained rushing water, and sealed damaged organs. More importantly, on-demand detachment and controllable adhesion were achieved by promoting swelling. In addition, CP-Gel with good biosafety significantly promotes seawater-immersed wound healing and is promising for use in water-contact wound care, organ sealing, and marine emergency rescue.

Space reconnaissance has become an important part of modernized combat system, and is the key to obtaining the information dominance in advanced technology warfare and then mastering the initiative on the battlefield. Taking the US military space reconnaissance system as an instance, this paper combs the development status from four aspects: space optical imaging reconnaissance system, space radar imaging reconnaissance system, stationary orbit space signal reconnaissance system and variable orbit space signal reconnaissance system. Combining with the application examples of the US military, it analyzes the technology utilization from the central network, peacetime-to-wartime transformation, joint spying and preliminary reconnaissance, and it summarizes the US military space reconnaissance technologies from four aspects: the collaborative technology of heterogeneous reconnaissance network, high-speed transmission technology of intelligence data, high-resolution penetrating imaging technology, high-precision target positioning technology. Finally, this paper analyzes the development trend of space reconnaissance from five aspects: the mi-niaturization of space reconnaissance satellites, integration of reconnaissance networks, anti-jamming and anti-destruction of reconnaissance systems, integration sharing of reconnaissance information and intelligentization of information analysis and decision making, so as to provide references for the construction, application and development of future space reconnaissance systems.

Abstract Background Low-dose IL-2 (Ld-IL2) has shown favorable therapeutic effects in systemic lupus erythematosus (SLE) therapy. However, previous clinical trials reported an SLE Responder Index-4 (SRI-4) response rate of 65.52%-68%, with approximately half failing to achieve the primary endpoint by week 24. Our study aims to determine the real-world use of Ld-IL2 and to identify determinants of its effectiveness in SLE. Methods We pooled data from 342 SLE patients undergoing sequential Ld-IL2 treatment, with 314 persisting for over 3 months were included in effectiveness and prediction analyses. All patients were categorized into responder (n = 136) and non-responder group (n = 178) according to SRI-4. Lupus Low Disease Activity State (LLDAS) was also analyzed to validate our results. Results Rash, lower complement 3 (C3), and renal involvement including urine protein, urine occult blood and urine casts emerged as prominent predictors of achieving SRI-4. Adjusting for baseline values using the ratio of change to baseline revealed significant differences in CD4 + T cell immune profiles between responders and non-responders. ROC analysis confirmed a satisfactory performance of rash, renal involvement, percentage change of CD4 + T cells, and C3 in predicting SRI-4, yielding an AUC of 0.933. LLDAS analysis showed that hematological involvements and lower CLA + Treg were potent predictive markers in LLDAS attainment. Conversely, renal involvement failed to have significant association in achieving LLDAS. The analysis of background therapy in SLE patients showed that MMF was more likely to reach the SRI-4 response with the combination of Ld-IL2. Conclusions These findings uncovered the predictors of Ld-IL2 treatment efficacy in SLE patients and provided guidance to physicians for rational utilization.

Abstract Greenhouses need to supply CO2 to crops while simultaneously emitting CO2. To effectively harness the dual functionality of greenhouses as a carbon source and carbon consumer, this work incorporates carbon capture and emissions trading into a multi‐energy greenhouse (MEG), which is equipped with various power and heat sources such as photovoltaic (PV) panels and a combined heat and power (CHP) unit and proposes that the captured CO2 should be used to feed crops on‐site. A low‐carbon economic operation method is proposed for the coordinated environment‐energy‐carbon management of the MEG, and it considers various factors, including the power purchase/carbon supply costs, carbon emissions trading income, temperature/humidity/light intensity and CO2 concentration requirements for crops, and operational constraints of various energy/environmental regulation equipment. The proposed method is validated using a tomato MEG. The results highlight the significant economic and environmental benefits of introducing carbon capture, emissions trading, and utilisation into MEGs.

Abstract The task of UAV-based maritime rescue object detection faces two significant challenges: accuracy and real-time performance. The YOLO series models, known for their streamlined and fast performance, offer promising solutions for this task. However, existing YOLO-based UAV maritime rescue object detection methods tend to prioritize high accuracy, often at the expense of real-time performance and ease of implementation and expansion. This study proposes a modular plug-and-play optimization approach based on the YOLOv8 framework, aiming to enhance real-time performance while maintaining high accuracy for UAV maritime rescue object detection. The proposed optimization modules are flexible, easy to implement, and extendable. In experiments on the large-scale publicly available SeaDronesSee dataset, our method achieved a 13.53% improvement in accuracy over YOLOv8x while reducing computational cost by 85.63%. Additionally, it surpassed the detection speed of the SeaDronesSee official code’s two-stage detector by over 20 times, while maintaining comparable accuracy. Furthermore, our analysis of the experimental results highlights differences in detection difficulty among various objects and potential biases within the dataset.

Abstract Objective Knee osteoarthritis (KOA) is usually bilateral. In many patients, the degree of bilateral knee degeneration varies, with one side involving multiple compartments and the other a single compartment degeneration. Therefore, the objective of this study was to compare the early clinical efficacy of simultaneous bilateral and staged total knee arthroplasty (TKA) combined with unicompartmental knee arthroplasty (UKA) in the treatment of bilateral KOA with different degrees. Methods We compared clinical data from 71 simultaneous bilateral TKA/UKA (SB-TKA/UKA) patients with 52 Staged TKA/UKA (Staged-TKA/UKA) patients. Staged-TKA/UKA is defined as TKA on one knee followed by UKA on the other knee. The comparison included Hospital for Special Surgery (HSS) score, range of motion(ROM), complication rate and prosthetic survival rate at the last follow-up between the two groups. Results The follow-up time of SB-TKA/UKA group was (69.08 ± 14.35) months, and that of Staged-TKA/UKA group was (73.25 ± 18.39) months. Staged-KA/UKA group had a shorter hospital stays, less hospitalization costs and shorter operating time (p 0.05). There was no significant difference in complication rate between the two groups (χ2 = 0.56, p = 0.454). For the TKA-side knee joint, there was no significant difference in the prosthetic survival rate (χ2 = 0.05, p = 0.824) and the prosthetic survival curve (χ2 = 0.052, p = 0.82) between the two groups. For UKA-side knee joint, there was no significant difference in prosthetic survival rate (χ2 = 0.08, p = 0.777) and prosthetic survival curve (χ2 = 0.074, p = 0.786) between the two groups. Conclusions Compared to Staged-TKA/UKA, SB-TKA/UKA has the same early clinical efficacy, shorter operating time and hospital stays, less hospitalization costs, and no increased postoperative complications and prosthesis revision rates. Therefore, SB-TKA/UKA may be recommended for patients who can tolerate simultaneous bilateral surgery as assessed before surgery.

Abstract In federated learning, secret sharing is a key technology to maintain the privacy of participants’ local models. Moreover, with the rapid development of quantum computers, existing federated learning privacy protection schemes based on secret sharing will no longer be able to guarantee the data security of participants in the post-quantum era. In addition, existing privacy protection methods have the problem of high communication and computational overhead. Although the multi-stage secret sharing scheme proposed by Pilaram et al. is one of the effective solutions to the above problems, existing studies have proven the privacy leakage risk of this scheme. This paper firstly designs a new lattice-based multi-stage secret sharing scheme Improved-Pilaram to solve the security problem, which allows participants to use public vectors to reconstruct different secret values without changing the secret sharing. Based on Improved-Pilaram, this article proposes a post-quantum secure federated learning scheme PQSF. PQSF uses double masking technology to encrypt model parameters and achieves mask reconstruction through secret sharing. Since Improved-Pilaram is multi-stage, participants do not need to update their local secret shares frequently during training. Analysis and experimental results show that the PQSF proposed in this paper reduces the communication complexity between participants and reduces the computational overhead by about 20% compared with existing solutions.

Abstract Background Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC. Methods This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m2 intravenous infusion, day 1; capecitabine 1000 mg/m2 oral administration, days 1–14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14–15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed. Discussion In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer. Trial registration This study was registered at www.clinicaltrials.gov . Trial registration number: NCT05972655. Date of registration: 31 July 2023.

Abstract Background As a result of the COVID-19 pandemic, we implemented a novel nurse-led symptom monitoring and virtual telehealth program for patients with advanced cancer on palliative care. Aims To evaluate the reach, effectiveness, adoption, implementation, maintenance and acceptability of our program. Methods This was a prospective study carried out in a cohort of patients with advanced cancer over the period of 3rd June 2020 to 22nd October 2021. Demographic characteristics, cancer diagnosis, and functional status of patients were collected upon recruitment. Patients were asked to complete a patient-reported outcome measure (the Integrated Palliative Care Outcome Scale, IPOS) prior to the first palliative care consult and subsequently every week for the duration of their participation in the program (12 weeks). The IPOS measures the severity of physical symptoms, emotional concerns, information, and financial needs. Participants’ utilization of healthcare services by participants 3 months before, during and 3 months after the telemedicine program was reviewed. At the end of the program, a client satisfaction questionnaire (CSQ-4) to survey participants’ experience with the telehealth program and their willingness to pay for this program was administered. Results Reach: The recruitment to adoption ratio of the program was 0.71. Acceptability:: Participants expressed satisfactory experience. Effectiveness: We noted that the severity of patients’ symptoms and number of emergency department visits decreased over time with nurse support. Adoption: we received referrals from 23 oncologists, yielding an adoption rate of 70%. Implementation: Of the 99 patients recruited for the program, 88.9% of them managed to complete their initial video consults as planned. 16% of them failed to complete the program due to factors such as patient demising. Maintenance: The declining rate of IPOS completion throughout the study period (98.9% at week 1 to 60.8% at week 12) demonstrated the difficulties in sustaining regular administration of self-reported patient outcome measures. Conclusion The telemedicine program was effective and acceptable. We noted challenges in sustaining the administration of patient reported outcome measures over time. Further studies on how we can improve the sustainability of symptom monitoring in a telehealth program for patients with advanced illnesses, under palliative care, should be conducted.

Abstract GLS4 is a first‐in‐class hepatitis B virus (HBV) capsid assembly modulator (class I) that is co‐administered with ritonavir to maintain the anticipated concentration required for the effective antiviral activity of GLS4. In this study, the first physiologically‐based pharmacokinetic (PBPK) model for GLS4/ritonavir was successfully developed. The predictive performance of the PBPK model was verified using data from 39 clinical studies, including single‐dose, multiple‐dose, food effects, and drug–drug interactions (DDI). The PBPK model accurately described the PK profiles of GLS4 and ritonavir, with predicted values closely aligning with observed data. Based on the verified GLS4/ritonavir model, it prospectively predicts the effect of hepatic impairment (HI) and DDI on its pharmacokinetics (PK). Notably, CYP3A4 inducers significantly influenced GLS4 exposure when co‐administered with ritonavir; co‐administered GLS4 and ritonavir significantly influenced the exposure of CYP3A4 substrates. Additionally, with the severity of HI increased, there was a corresponding increase in the exposure to GLS4 when co‐administered with ritonavir. The GLS4/ritonavir PBPK model can potentially be used as an alternative to clinical studies or guide the design of clinical trial protocols.

Abstract Background Osteoporosis with pathological fractures is a significant public health issue, contributing to morbidity, disability, diminished quality of life, and increased mortality. Understanding mortality trends related to this condition is crucial for developing effective interventions to reduce mortality and improve healthcare outcomes. This study aimed to analyze trends and causes of death associated with osteoporosis and pathological fractures in the United States using a multi-cause approach. Methods Annual death and age-standardized mortality rate (ASMR) data from 1999 to 2020 were obtained from the Centers for Disease Control and Prevention (CDC) mortality database. Death certificates listing ICD-10 M82 (osteoporosis with pathological fracture) as an underlying or related cause of death were analyzed. Epidemiological data were analyzed, and the ASMR data were calculated for each year, and trends were assessed using the Cochran-Armitage trend test. Results From 1999 to 2020, there were 40,441 deaths related to osteoporosis with pathological fractures in the United States, with a female-to-male ratio of 5.6:1. Among these, 12,820 deaths (31.7%) listed osteoporosis with pathological fractures as the underlying cause of death (UCD), yielding a female-to-male ASMR ratio of approximately 5.0-7.7:1. When classified as a non-UCD, the ASMR ratio was approximately 4.8–6.2:1. At the same time, we found that the total number of deaths classified as UCD and multiple causes of death (MCD), but the trend ratio of the two groups in different years did not change statistically significant (P > 0.05), and the ASMR of both groups showed a downward trend. The UCD-to-MCD ratio increased between 1999 and 2007, then decreased from 2007 to 2020. As MCD, the number of female deaths was more than that of male, and both showed a decreasing trend, but there was no statistical significance in the change of trend ratio in different years (P > 0.05). Deaths were predominantly concentrated in individuals over 75 years of age, with those over 84 years being the most affected. The number of deaths in different age groups showed a decreasing trend, and the change of trend ratio in different years was statistically significant (P

Abstract Background Ocular toxicity is a severe adverse effect that limits the chronic clinical use of the antiarrhythmic drug amiodarone. Here, we aimed to evaluate the cytoprotective effect of artemisinin and explore the potential signalling pathways in human retinal pigment epithelial (RPE) cell cultures. Methods D407 cell cultures were exposed to amiodarone and the impact of artemisinin was evaluated. The key parameters included lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) generation, and the mitochondrial membrane potential (MMP). We also assessed the protein levels of cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), phosphorylated adenosine monophosphate-activated protein kinase (AMPK)ɑ (p-AMPK), calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), and nuclear factor erythroid 2-related factor 2 (Nrf2). Results Artemisinin reduced the cytotoxicity induced by amiodarone, as reflected by decreased LDH release, ROS generation, and MMP disruption. Additionally, artemisinin increased p-AMPK, CaMKK2, and Nrf2 protein levels. Inhibition of AMPK, CaMKK2, or Nrf2 abolished the cytoprotective effect of artemisinin. AMPK activation and Nrf2 knockdown further supported its protective role. Conclusions Artemisinin protected RPE cells from amiodarone-induced damage via the CaMKK2/AMPK/Nrf2 pathway. The in vivo experiments in mice confirmed its efficacy in preventing retinal injury caused by amiodarone. These results suggest that an artemisinin-based eye formulation could be repurposed for treating amiodarone-induced ocular toxicity.

Abstract Mitochondrial dysfunction is a significant contributor to podocyte injury in diabetic kidney disease (DKD). While previous studies have shown that PVT1 might play a vital role in DKD, the precise molecular mechanisms are largely unknown. By analyzing the plasma and kidney tissues of DKD patients, we observed a significant upregulation of PVT1 expression, which exhibited a positive correlation with albumin/creatinine ratios and serum creatinine levels. Then, we generated mice with podocyte-specific deletion of PVT1 (Nphs2-Cre/Pvt1 flox/flox ) and confirmed that the deletion of PVT1 suppressed podocyte mitochondrial dysfunction and inflammation in addition to ameliorating diabetes-induced podocyte injury, glomerulopathy, and proteinuria. Subsequently, we cultured podocytes in vitro and observed that PVT1 expression was upregulated under hyperglycemic conditions. Mechanistically, we demonstrated that PVT1 was involved in mitochondrial dysfunction by interacting with TRIM56 post-transcriptionally to modulate the ubiquitination of AMPKα, leading to aberrant mitochondrial biogenesis and fission. Additionally, the release of mtDNA and mtROS from damaged mitochondria triggered inflammation in podocytes. Subsequently, we verified the important role of TRIM56 in vivo by constructing Nphs2-Cre/Trim56flox/flox mice, consistently with the results of Nphs2-Cre/Pvt1 flox/flox mice. Together, our results revealed that upregulation of PVT1 could promote mitochondrial dysfunction and inflammation of podocyte by modulating TRIM56, highlighting a potential novel therapeutic target for DKD.

Abstract Evidence-based data regarding the timing of the application of invasive mechanical ventilation among adults with septic shock is insufficient. The guidelines fail to provide clear advice about the optimal time to initiate this support. Consequently, we aimed to investigate whether early intubation could improve survival rates in septic shock patients. We conducted a retrospective analysis of the MIMIC-IV database to evaluate the effectiveness of early intubation on mortality in a cohort of septic shock patients. Adults diagnosed with septic shock, according to the Sepsis-3 definition, were included. They were categorized into an early intubation group (first 8 h after vasopressor initiation) and a non-early intubation group (unexposed). A propensity score matching (PSM) analysis was used to balance the baseline characteristics between the two groups. The primary outcomes were 30-day and 90-day all-cause mortality rates. In addition, we employed the restricted cubic spline to analyze the potential non-linear relationship between the timing of intubation and 30-day or 90-day all-cause mortality. A total of 6864 adult patients, of whom 2048 were intubated in the first 8 h, were evaluated in the final cohort. Following a 1:1 PSM procedure, 2786 patients were successfully paired. At 30 days, 288 of 1393 patients (20.7%) in the early intubation group and 381 of 1393 patients (27.4%) in the non-early intubation group had died (hazard ratio [HR] 0.717; 95% confidence interval [CI] 0.616–0.836; p

Abstract Small molecular RNAs, including microRNA (miRNA) and small interfering RNA (siRNA), participate in the regulation of gene expression. As powerful regulators, miRNAs, take part in posttranscriptional regulation of gene expression and play important roles in the diagnosis and treatment of cancer. Meanwhile, siRNA can induce sequence-specific gene silencing, thus being able to inhibit tumorigenesis by suppressing the expression of their targeted proto-oncogenes. Small RNAs (including naked miRNAs and siRNAs) are easily degraded by circulating RNAase, which can be retarded through the package of nanoparticles. Therefore, nanoparticles help tumor therapy by regulating targeted genes of small RNAs. Here, we reviewed the effects of small RNAs on gene expression; the advantages, disadvantages, and targeted modification of nanoparticles as carriers transporting small RNAs; and the application of nanocarriers delivering small RNA for cancer-targeted therapy.

Abstract Objective There is growing evidence that simultaneous bilateral open wedge high tibial osteotomy(SBOWHTO) and simultaneous bilateral unicompartmental knee arthroplasty(SBUKA) is an effective surgical treatment for bilateral medial knee osteoarthritis (MKOA). However, which intervention is more beneficial for bilateral MKOA patients remains unknown. Therefore, the aim of this study was to compare the effectiveness of these two strategies through early clinical outcomes, complication rates, and prosthetic survival. Methods The clinical data of 60 patients with bilateral MKOA admitted to the Affiliated Hospital of Qingdao University from January 2018 to December 2022 were retrospectively analyzed, and they were divided into SBOWHTO group (n = 28) and SBUKA group (n = 32) according to different treatment methods. Clinical relevant indexes, Hospital for Special Surgery (HSS) score, Knee Society Knee (KSS) score, range of motion(ROM), postoperative complications and prosthetic survival rate were compared between the two groups. Results Patients in the SBOWHTO group were followed up for 27 to 50 months, with an average of (37.18 ± 6.84) months. Patients in the SBUKA group were followed up for 24 to 59 months, with an average of (39.38 ± 9.74) months. There were no significant differences in postoperative KSS, HSS and ROM between SBOWHTO group and SBUKA group (p > 0.05). There was no significant difference in complication rate between the two groups (p = 0.721). There was no significant difference in prosthetic survival rate (p = 0.622) and prosthetic survival curve (χ2 = 0.546, p = 0.46) between the two groups. Conclusions This study compared early clinical outcomes, complication rates, and prosthesis retention rates after SBOWHTO and SBUKA, and found that the early clinical benefits of SBOWHTO and SBUKA were comparable in patients with bilateral MKOA.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is often diagnosed at advanced stages due to the inherent limitations of current screening methodologies. Central to evaluating tumor invasion and prognostic assessment in ESCC is the integrity of the basement membrane (BM). However, current research on the implications of BM-related genes (BMRGs) in diagnosing ESCC remains sparse. Methods We performed a comprehensive analysis using single-cell RNA-sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, alongside gene expression profiles acquired from GEO and The Cancer Genome Atlas (TCGA) databases. This identified differentially expressed BMRGs in ESCC. Employing LASSO, RF, and SVM-RFE, we selected potential BM biomarkers and crafted a diagnostic nomogram for ESCC, validated by ROC curves and AUC values. We also explored immune infiltration and biological mechanisms through consensus clustering and GSVA, and utilized single cell trajectory analysis and GSCALite to study gene distributions and pathways. In vitro experiments further elucidated the role of these genes in ESCC carcinogenesis. Results Here, we discovered that ESCC cell types exhibited markedly elevated BM-related scores. Our analysis pinpointed seven BM genes upregulated and linked to immune infiltration, showcasing unique gene expression profiles and varying immune cell densities across the BM-related subtypes. Furthermore, a robust positive correlation was observed between these genes expression and EMT activity. The knockdown of BGN significantly suppressed cell proliferation, migration, invasion, while also augmenting cell viability following chemotherapy drug treatment. Conclusion Our study identified seven key BMRGs (BGN, LAMB3, SPARC, MMP1, LUM, COL4A1, and NELL2) and established a diagnostic nomogram for ESCC. Of noteworthy significance is the discovery of BGN as a promising drug target, indicating a novel strategy for future clinical combination therapies in ESCC.

Abstract Many patients with diabetes struggle with post-meal high blood glucose due to missed or untimely meal-related insulin doses. To address this challenge, our research aims to: (1) study mealtime patterns in patients with type 1 diabetes using wearable insulin pump data, and (2) develop personalized models for predicting future mealtimes to support timely insulin dose administration. Using two independent datasets with over 45,000 meal logs from 82 patients with diabetes, we find that the majority of people ( $$\sim$$ ∼ 60%) have irregular and inconsistent mealtime patterns that change notably through the course of each day and across months in their own historical data. We also show the feasibility of predicting future mealtimes with personalized LSTM-based models that achieve an average F1 score of > 95% with less than 0.25 false positives per day. Our research lays the groundwork for developing a meal prediction system that can nudge patients with diabetes to administer bolus insulin doses before meal consumption to reduce the occurrence of post-meal high blood glucose.

ABSTRACT: We investigated the short- and long-term effects of different forage types supplemented in preweaning dairy calves on growth performance, blood metabolites, rumen fermentation, bacterial community, and milk production during first lactation. A total of 60 healthy 30-d-old female Holstein calves were blocked by birth date and body weight and randomly assigned to 1 of 3 groups (n = 20): normal milk and pelleted starter feeding (CON), supplemented with chopped oat hay (OAH; 75.0 g/d per calf [DM basis]), or alfalfa hay (ALF; 75.0 g/d per calf [DM basis]). The forage supplementation started when calves were 30 d old (d 1 of the experimental period) and ended when they were 73 d old (d 44 of the experimental period, when calves were weaned). Milk and feed intakes and fecal consistency scores were recorded daily. Growth performance, rumen fluid, and blood samples were collected biweekly. After weaning, all the calves were integrated with the same barn and diets. After calving, the milk production was recorded daily. During the experimental period, the OAH group had greater solid feed and total DM intakes and greater rumen pH than the CON group (P ≤ 0.04), but had lower forage intake and CP digestibility than the ALF group (P ≤ 0.04). The ALF group had higher rumen pH and blood BHB concentration (P ≤ 0.04), lower fecal score (P = 0.02), and greater ether extract digestibility (P = 0.02) than the CON group. The ALF and OAH groups had lower concentrations of ruminal total VFA (P = 0.01). Still, the ALF group had a greater proportion of acetate and a relative abundance of cellulose degradation-related bacteria (Lachnoclostridium_1 and Oribacterium) and a lower relative abundance of inflammation-related bacteria (Erysipelotrichaceae_UCG-009) in the rumen compared with CON. Interestingly, the average milk production from 6 to 200 DIM was greater in the ALF group (P < 0.01), even though no significant effects were found on the rumen fermentation parameters and blood metabolites at 200 DIM. Generally, alfalfa hay supplementation in preweaning dairy calves had positive effects in the short- and long-term for rumen development, health status, and future milk production.

Digital light processing (DLP)-based bioprinting technology holds immense promise for the advancement of hydrogel constructs in biomedical applications. However, creating high-performance hydrogel constructs with this method is still a challenge, as it requires balancing the physicochemical properties of the matrix while also retaining the cellular activity of the encapsulated cells. Herein, we propose a facile and practical strategy for the 3D bioprinting of high-performance hydrogel constructs through the in-situ birth of stem cell spheroids. The strategy is achieved by loading the cell/dextran microdroplets within gelatin methacryloyl (GelMA) emulsion, where dextran functions as a decoy to capture and aggregate the cells for bioprinting while GelMA enables the mechanical support without losing the structural complexity and fidelity. Post-bioprinting, the leaching of dextran results in a smooth curved surface that promotes in-situ birth of spheroids within hydrogel constructs. This process significant enhances differentiation potential of encapsulated stem cells. As a proof-of-concept, we encapsulate dental pulp stem cells (DPSCs) within hydrogel constructs, showcasing their regenerative capabilities in dentin and neovascular-like structures in vivo. The strategy in our study enables high-performance hydrogel tissue construct fabrication with DLP-based bioprinting, which is anticipated to pave a promising way for diverse biomedical applications.

Optimizing blasting parameters is of paramount importance in minimizing overbreak during tunneling. Hence, this paper proposed an intelligent approach, which integrates separate parameter optimization based on varying rock mass qualities, with the objective of reducing overbreak. This novel intelligent method constructs a comprehensive model with three distinct functions, which can provide precise overbreak prediction, analyze the mechanisms by which input parameters influence overbreak, and integrate feature importance into the blasting parameters optimization process. First, the hyperparameters of seven tree-based algorithms were optimized using the Sparrow Search Algorithm (SSA), and the best predictive model was selected by comparing various performance metrics. Then, the importance and influencing mechanisms of input features on overbreak were revealed through the utilization of the Shapley Additive Explanation. Subsequently, interactions among crucial parameters were investigated, and their design values were recommended. Finally, a novel parameter optimization method was employed to reduce overbreak, which combines the conclusions drawn from the importance analysis of input features with SSA through three key steps: modification of the initial position, expanding the search scope, and neighborhood perturbation. Compared to the unimproved methods, the proposed approach can significantly reduce post-blast overbreak areas in different sections of the tunnel by 12.8 % and 16.4 %, respectively.

The present work focused on examining the function of rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) in jejunal oxidative resistance, integrity and immune function in the ovine foetal model of intrauterine growth restriction (IUGR). Thirty-two twin-bearing Hu ewes at d 35 of gestation were randomised as 4 treatment groups (n = 8 each): Control (CON), received 100% of the recommended National Research Council (NRC) for pregnancy; Restricted (RES), received 50% of the recommended NRC for pregnancy; RES + ARG, RES ewes added with 20 g/d of RP-Arg; or RES + NCG treatment, RES ewes added with 5 g/d of NCG. Foetal jejunal samples were collected on d 110 of pregnancy and were assayed for biomarkers of oxidative damage, integrity and immune function. The villus height was elevated (p

ObjectivesThe natural draft cooling towers with flue gas injection (NDCT-FGI) is a crucial retrofitting technique for enhancing the efficiency of thermal power plants. However, its operational impacts on existing systems are significant and cannot be overlooked. Therefore, the current status of NDCT-FGI technology and its problems in operation were analyzed, and the countermeasures were put forward.MethodsThrough comprehensive analysis of the existing research, the causes and formation mechanism of environmental impact, cooling tower corrosion, and deterioration of circulating cooling water quality caused by the technical transformation of NDCT-FGI were discussed.ResultsThe protective distance can be reasonably set by the simulation results of flue gas emission trajectory and pollutant landing concentration by computational fluid dynamics (CFD). Installation of baffles at the tower top can prevent flue gas washdown during the extreme weather conditions. Different anticorrosive coatings are recommended for various parts of the cooling tower to extend its service life. To control and optimize cooling water quality, the advanced water treatment techniques are necessary for optimizing chemical dosing, and the management of effluent and makeup water must be carefully controlled to ensure operational sustainability.ConclusionsBy implementing appropriate and effective countermeasures, the negative impacts of NDCT-FGI retrofitting can be mitigated, thereby enhancing both the environmental and economic benefits for thermal power plants.

In non-small cell lung cancer (NSCLC), as an improtant oncogenic driver gene, epidermal growth factor receptor exon 20 insertion (EGFR ex20ins) has a unique protein structure and is primarily drug-resistant to traditional EGFR-tyrosine kinase inhibitors (EGFR-TKIs). In recent years, exploration of targeted therapy for EGFR ex20ins has never stopped. Firstly Mobocertinib and Amivantamab obtained approval from U.S. Food and Drug Administration (FDA) for EGFR ex20ins mutant NSCLC patients, then other drugs, such as Sunvozertinib, made breakthroughs and combination therapies also obtained gains. Multi-pronged measures are hopeful to overcome EGFR ex20ins drug resistance. As mentioned above, it’s definitely important to gain deeper understanding of molecular mechanism of EGFR ex20ins and assess effect and difference between novel drugs. This review is devoted to make a summary about newest achievement so to provide valuable reference about precise therapy for patients with EGFR ex20ins.

Multifunctional metastructure integrated broadband microwave absorption and effective mechanical resistance has attracted much attention. However, multifunctional performance is limited by the lack of theoretical approaches to integrated design. Herein, a multi-layer impedance gradient honeycomb (MIGH) was designed through theoretical analysis and simulation calculation, and fabricated using 3D printing technique. A theoretical calculation strategy for impedance gradient structure was established based on the electromagnetic parameter equivalent method and the multi-layer finite iterative method. The impedance of MIGH was analyzed by the theoretical calculation strategy to resolve the broadband absorption. Intrinsic loss mechanism of matrix materials and distributions of electric fields, magnetic fields and power loss were analyzed to investigate the absorption mechanism. Experimental results indicated that a 15 ​mm thick designed metastructure can achieve the absorption more than 88.9% in the frequency range of 2-18 ​GHz. Moreover, equivalent mechanical parameters of MIGH was calculated by integral method according to the Y-shaped model. Finite Element analysis of stress distributions were carried out to predict the deformation behavior. Mechanical tests demonstrate that MIGH achieved the compression modulus of 22.89 ​MPa and flexure modulus of 17.05 ​MPa. The integration of broadband electromagnetic absorption and effective mechanical resistance was achieved by the proposed design principle and fabrication methodology.

Abstract RNase H1 has been acknowledged as an endoribonuclease specializing in the internal degradation of the RNA moiety within RNA–DNA hybrids, and its ribonuclease activity is indispensable in multifaceted aspects of nucleic acid metabolism. However, the molecular mechanism underlying RNase H1-mediated hybrid cleavage remains inadequately elucidated. Herein, using single-molecule approaches, we probe the dynamics of the hybrid cleavage by Saccharomyces cerevisiae RNase H1. Remarkably, a single RNase H1 enzyme displays 3′-to-5′ exoribonuclease activity. The directional RNA degradation proceeds processively and yet discretely, wherein unwinding approximately 6-bp hybrids as a prerequisite for two consecutive 3-nt RNA excisions limits the overall rate within each catalytic cycle. Moreover, Replication Protein A (RPA) reinforces RNase H1’s 3′-to-5′ nucleolytic rate and processivity and stimulates its 5′-to-3′ exoribonuclease activity. This stimulation is primarily realized through the pre-separation of the hybrids and consequently transfers RNase H1 to a bidirectional exoribonuclease, further potentiating its cleavage efficiency. These findings unveil unprecedented characteristics of an RNase and provide a dynamic view of RPA-enhanced processive hybrid cleavage by RNase H1.

Abstract Background Cabbage Fusarium wilt (CFW) is a devastating disease caused by the soil-borne fungus Fusarium oxysporum f. sp. conglutinans (Foc). One of the optimal measures for managing CFW is the employment of tolerant/resistant cabbage varieties. However, the interplay between plant genotypes and the pathogen Foc in shaping the rhizosphere microbial community, and the consequent influence of these microbial assemblages on biological resistance, remains inadequately understood. Results Based on amplicon metabarcoding data, we observed distinct differences in the fungal alpha diversity index (Shannon index) and beta diversity index (unweighted Bray–Curtis dissimilarity) within the rhizosphere of the YR (resistant to Foc) and ZG (susceptible to Foc) cabbage varieties, irrespective of Foc inoculation. Notably, the Shannon diversity shifts in the resistant YR variety were more pronounced following Foc inoculation. Disease-resistant plant variety demonstrate a higher propensity for harboring beneficial microorganisms, such as Pseudomonas, and exhibit superior capabilities in evading harmful microorganisms, in contrast to their disease-susceptible counterparts. Furthermore, the network analysis was performed on rhizosphere-associated microorganisms, including both bacteria and fungi. The networks of association recovered from YR exhibited greater complexity, robustness, and density, regardless of Foc inoculation. Following Foc infection in the YR rhizosphere, there was a notable increase in the dominant bacterium NA13, which is also a hub taxon in the microbial network. Reintroducing NA13 into the soil significantly improved disease resistance in the susceptible ZG variety, by directly inhibiting Foc and triggering defense mechanisms in the roots. Conclusions The rhizosphere microbial communities of these two cabbage varieties are markedly distinct, with the introduction of the pathogen eliciting significant alterations in their microbial networks which is correlated with susceptibility or resistance to soil-borne pathogens. Furthermore, we identified a rhizobacteria species that significantly boosts disease resistance in susceptible cabbages. Our results indicated that the induction of resistance genes leading to varied responses in microbial communities to pathogens may partly explain the differing susceptibilities of the cabbage varieties tested to CFW. Video Abstract

Abstract Background Tumor recurrence and mortality rates remain challenging in cancer patients despite comprehensive treatment. Neoadjuvant chemotherapy and immunotherapy aim to eliminate residual tumor cells, reducing the risk of recurrence. However, drug resistance during neoadjuvant therapy is a significant hurdle. Recent studies suggest a correlation between RNA methylation regulators (RMRs) and response to neoadjuvant therapy. Methods Using a multi-center approach, we integrated advanced techniques such as single-cell transcriptomics, whole-genome sequencing, RNA sequencing, proteomics, machine learning, and in vivo/in vitro experiments. Analyzing pan-cancer cohorts, the association between neoadjuvant chemotherapy/immunotherapy effectiveness and RNA methylation using single-cell sequencing was investigated. Multi-omics analysis and machine learning algorithms identified genomic variations, transcriptional dysregulation, and prognostic relevance of RMRs, revealing distinct molecular subtypes guiding pan-cancer neoadjuvant therapy stratification. Results Our analysis unveiled a strong link between neoadjuvant therapy efficacy and RNA methylation dynamics, supported by pan-cancer single-cell sequencing data. Integration of omics data and machine learning algorithms identified RMR genomic variations, transcriptional dysregulation, and prognostic implications in pan-cancer. High-RMR-expressing tumors displayed increased genomic alterations, an immunosuppressive microenvironment, poorer prognosis, and resistance to neoadjuvant therapy. Molecular investigations and in vivo/in vitro experiments have substantiated that the JAK inhibitor TG-101,209 exerts notable effects on the immune microenvironment of tumors, rendering high-RMR-expressing pan-cancer tumors, particularly in pancreatic cancer, more susceptible to chemotherapy and immunotherapy. Conclusions This study emphasizes the pivotal role of RMRs in pan-cancer neoadjuvant therapy, serving as predictive biomarkers for monitoring the tumor microenvironment, patient prognosis, and therapeutic response. Distinct molecular subtypes of RMRs aid individualized stratification in neoadjuvant therapy. Combining TG-101,209 adjuvant therapy presents a promising strategy to enhance the sensitivity of high-RMR-expressing tumors to chemotherapy and immunotherapy. However, further validation studies are necessary to fully understand the clinical utility of RNA methylation regulators and their impact on patient outcomes.

This is an article in the field of mining engineering. The Southern Xizang is one of the main distribution areas of high temperature geothermal zones in China with rich geothermal resources. The chemical analysis and test results of the geothermal water show that the lithium content in the geothermal water of the high temperature geothermal zone in Southern Xizang can reach 34.51 mg/L, and the relative abundance of geothermal lithium is obviously better than that of the world's typical plateau Salt Lake brines, such as Clayton Valley in the Western Plateau of North America and Uyuni in the Andes Plateau of South America. The lithium magnesium ratio is mostly less than 3, which is conducive to lithium extraction from brine. The areas with high lithium content in the geothermal water of the high temperature geothermal zones in Southern Xizang are all distributed in the the Yarlung Zangbo River suture zone and the areas to the south, consistent with the distribution range of lithium rich rocks. At the same time, the Yarlung Zangbo River suture zone and its south area have more Cl-Na geothermal water than the north, and the south has higher TDS and longer circulation path. Based on the stable isotopic composition of hydrogen and oxygen in geothermal water and the provenance of lithium in the surrounding lithium-rich Salt Lake brine, it is inferred that the main sources of lithium in the geothermal water are leaching of lithium-rich rocks by geothermal water and lithium-rich magmatic hydrothermal solutions formed during magmatic differentiation.

Objective: To investigate the effect and mechanism of Hippophae rhamnoides flavone (HRF) on polycystic ovarian syndrome (PCOS) in rats, and to provide new ideas for the prevention and treatment of PCOS. Methods: A PCOS rat model was duplicated by giving rats a high-fat diet combined with the intragastric administration of letrozole, and the model rats were randomly divided into model group, low-dose HRF group (200 mg/kg HRF), high-dose HRF group (400 mg/kg HRF) and metformin group (100 mg/kg). Changes in the related indicators were detected on the 21 d after the rats were administered with the different agents by gavage. Results: Compared with that in the model group, the ovarian index, the percentage of interestrus temporal image, the fasting blood glucose (FBG) level, the fasting insulin (FINS) content, the insulin resistance index (HOMA-IR), the activities of serum luteinizing hormone (LH) and testosterone (T), the levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and C reactive protein (CRP) of rats in low- and high-dose HRF groups were respectively decreased significantly (P

Abstract A body area network involving wearable sensors distributed around the human body can continuously monitor physiological signals, finding applications in personal healthcare and athletic evaluation. Existing solutions for near-field body area networks, while facilitating reliable and secure interconnection among battery-free sensors, face challenges including limited spectral stability against external interference. Here we demonstrate a textile metamaterial featuring a coaxially-shielded internal structure designed to mitigate interference from extraneous loadings. The metamaterial can be patterned onto clothing to form a scalable, customizable network, enabling communication between near-field reading devices and battery-free sensing nodes placed within the network. Proof of concept demonstration shows the metamaterial’s robustness against mechanical deformation and exposure to lossy, conductive saline solutions, underscoring its potential applications in wet environments, particularly in athletic activities involving water or significant perspiration, offering insights for the future development of radio frequency components for a robust body area network at a system level.

Abstract Astragaloside IV, a prime active component of Astragalus membranaceus, has potential as a neuroprotectant. We aimed to identify the active ingredients in A. membranaceus and assess if Astragaloside IV can improve cerebral ischemia-reperfusion injury (CIRI) cell apoptosis by reducing P-Src and P-GRK2 via ryanodine receptor (RyR) expression inhibition. We used bioinformatics analysis to examine the effects of A. membranaceus on ischemic stroke. We studied brain samples from middle cerebral artery occlusion (MCAO) mice treated with normal saline, Astragaloside IV, and sham mice for pathology and Western blot tests. We also tested PC12 cells in vitro with or without Astragaloside IV or GSK180736A using Western blotting and fluorescence assays. Our bioinformatics analysis suggested a possible association between A. membranaceus, calcium ion pathways, and apoptosis pathways. Western blot data indicated Astragaloside IV significantly decreased RyR, p-Src, and downstream phosphorylated GRK2, PLC, CaMKII, and IP3R levels in MCAO mice brains. Astragaloside IV also considerably inhibited pro-apoptotic and oxidative stress-associated proteins’ expression while boosting anti-apoptotic protein expression. The results suggest Astragaloside IV can inhibit RyR expression, subsequently reducing brain cell apoptosis.

Abstract Background Addressing presbyopia in the aging population, particularly in non-cataractous patients, remains a challenge. This study evaluates the outcomes of refractive lens exchange (RLE) with AT LISA tri 839MP trifocal intraocular lens (IOL) implantation in a Chinese presbyopic population without cataracts. Methods The study included 164 eyes from 82 patients undergoing bilateral RLE at Peking Union Medical College Hospital. Comprehensive evaluations encompassed visual acuities, refraction, ocular aberrometry, and subjective outcomes via the VF-14 questionnaire. The focus was on postoperative visual performance, refractive outcomes, safety, objective optical quality, and patient satisfaction. Results 100%, 90.2%, and 89.0% of patients achieved binocular UDVA, UNVA, and UIVA of logMAR 0.1 or better at 6 months postoperatively. 97.6% of eyes were within ± 1.00 D of emmetropia postoperatively. Optical quality assessments showed increases in modulation transfer function and Strehl ratios (p

Codonopsis pilosula (known as dangshen) is experiencing a serious replant disease caused by continuous monoculture in its main and endemic cultivation region in Dingxi, China. In this study, changes in physicochemical properties, fungal microbiomes, and isolated strains were investigated in the rhizosphere soil of 1-, 2-, 3-, and 5-year continuous monoculture natural fields. It was observed that wilted seedlings and a variety of root rot diseases occurred after the third year of continuous monoculture in the field. The soil-available potassium content and the pH value decreased significantly in the 3- and 5-year fields. Using Illumina sequencing, it was demonstrated that the 3- and 5-year fields had a higher diversity of fungal communities compared with the 1- and 2-year fields. At the genus level, abundance of some potentially pathogenic fungal taxa also increased. A total of 33 isolated strains belonging to the Fusarium species complexes Plectosphaerella cucumerina, Paraphoma ledniceana, Alternaria alstroemeriae, Mucor hiemalis, and Clonostachys rosea were obtained from the roots in 3- and 5-year fields. The correlation analysis revealed that the abundance of the fungal community at the genus level was positively correlated with the available phosphorus, total nitrogen, and soil organic matter. The results revealed that continuous monoculture has a negative impact on the fungal community and enriches potential pathogenic fungi in the rhizosphere of C. pilosula.

Abstract Background Chronic kidney disease (CKD) and its associated end-stage renal disease (ESRD) are significant health problems that pose a threat to human well-being. Renal fibrosis is a common feature and ultimate pathological outcome of various CKD leading to ESRD. The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) is a refined compound formulated by our research group, which has been clinically administered for over a decade and has demonstrated the ability to improve the inflammatory state of various acute or chronic kidney diseases. However, the underlying mechanism by which A&P ameliorates renal fibrosis remains unclear. Methods We established a mouse model by surgically ligating the unilateral ureter to induce renal injury in vivo. And we utilized renal in situ electroporation of a plasmid with low LncRNA A33 expression to establish the unilateral ureteral obstruction(UUO)mouse model. In vitro, we stimulated primary tubular epithelial cells(pTEC) injury using TGF-β1, siRNA-A33, and pcDNA3.1-A33 plasmids were transfected into pTECs to respectively knockdown and overexpress LncRNA A33, and both in vitro and in vivo models were intervened with A&P. Results The results demonstrated that A&P effectively alleviated renal fibrosis in mice. Subsequent findings indicated high expression of LncRNA A33 in the kidneys of UUO mice and TGF-β1-induced renal tubular cells. In situ, renal electroporation of a plasmid with reduced LncRNA A33 expression revealed that inhibiting LncRNA A33 significantly improved renal fibrosis in UUO mice. Moreover, A&P effectively suppressed LncRNA A33 expression both in vitro and in vivo. Subsequent downregulation of LncRNA A33 in renal tubular epithelial cells resulted in the downregulation of numerous fibrotic markers, a significant inhibition of LncRNA A33, and a notable reduction in downstream ferroptosis signaling. Cell experiments demonstrated that A&P improved renal fibrosis in UUO mice by inhibiting LncRNA A33 and downregulating ferroptosis signaling. Conclusion Through the inhibition of LncRNA A33 and subsequent downregulation of ferroptosis signaling, A&P showed potential as a therapeutic approach for improving renal fibrosis in UUO mice, providing a potential treatment avenue for CKD.

Abstract Objectives To develop and validate a novel interpretable artificial intelligence (AI) model that integrates radiomic features, deep learning features, and imaging features at multiple semantic levels to predict the prognosis of intracerebral hemorrhage (ICH) patients at 6 months post-onset. Materials and methods Retrospectively enrolled 222 patients with ICH for Non-contrast Computed Tomography (NCCT) images and clinical data, who were divided into a training cohort (n = 186, medical center 1) and an external testing cohort (n = 36, medical center 2). Following image preprocessing, the entire hematoma region was segmented by two radiologists as the volume of interest (VOI). Pyradiomics algorithm library was utilized to extract 1762 radiomics features, while a deep convolutional neural network (EfficientnetV2-L) was employed to extract 1000 deep learning features. Additionally, radiologists evaluated imaging features. Based on the three different modalities of features mentioned above, the Random Forest (RF) model was trained, resulting in three models (Radiomics Model, Radiomics-Clinical Model, and DL-Radiomics-Clinical Model). The performance and clinical utility of the models were assessed using the Area Under the Receiver Operating Characteristic Curve (AUC), calibration curve, and Decision Curve Analysis (DCA), with AUC compared using the DeLong test. Furthermore, this study employs three methods, Shapley Additive Explanations (SHAP), Grad-CAM, and Guided Grad-CAM, to conduct a multidimensional interpretability analysis of model decisions. Results The Radiomics-Clinical Model and DL-Radiomics-Clinical Model exhibited relatively good predictive performance, with an AUC of 0.86 [95% Confidence Intervals (CI): 0.71, 0.95; P

Abstract Objective The practice of simultaneous bilateral unicompartmental knee arthroplasty (SBUKA) remains a topic of debate, particularly in patients with obesity. Thus, the purpose of this study was to assess the impact of body mass index (BMI) on the 30-day complication rate and the survival rate of the implant following SBUKA. Methods We retrospectively examined the clinical records of 245 patients (490 knees) who underwent SBUKA at the Affiliated Hospital of Qingdao University and the Third Hospital of Hebei Medical University between January 2010 and December 2020. Patients were categorised based on their BMI at the time of surgery into four groups: normal weight (BMI 18.5 to 22.9 kg/m2), overweight (BMI 23.0 to 24.9 kg/m2), obese (BMI 25.0 to 29.9 kg/m2), and severely obese (BMI ≥30 kg/m2). Variables such as length of hospital stay, duration of surgery, and costs of hospitalisation were compared across all groups. Additionally, we recorded the 30-day postoperative complication rate and the time from surgery to any required revision. The Kaplan-Meier survival analysis was employed to evaluate and compare the implant survival rates. Results The follow-up period for the 245 patients ranged from 39 to 114 months, with an average of 77.05±18.71 months. The incidence of complications within 30 days post-surgery did not significantly differ across the groups (χ2 = 1.102, p = 0.777). The implant survival rates from the lowest to the highest BMI groups were 97.14%, 93.9%, 94.44%, and 96.43%, respectively. Both the rate of implant revision (χ2 =1.612, p = 0.657) and the survival curves of the implants (p = 0.639) showed no statistically significant differences among the groups. Conclusions BMI did not influence the 30-day complication rate nor the survival rate of implants following SBUKA, suggesting that SBUKA should not be contraindicated based on BMI alone.

Abstract The outcomes of patients with sepsis are influenced by the contractile function of the right ventricle (RV), but the impact of cardiopulmonary interaction in ICU-mortality of sepsis patients remains unclear. This study aims to investigate the ICU-mortality impact of right ventricular-pulmonary artery (RV-PA) coupling in patients with sepsis. We employed echocardiography to assess patients with sepsis within the initial 24 h of their admission to the ICU. RV-PA coupling was evaluated using the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio. A total of 92 subjects were enrolled, with 55 survivors and 37 non-survivors. TAPSE/PASP ratio assessed mortality with an area under the curve (AUC) of 0.766 (95% CI 0.670–0.862) and the optimal cutoff value was 0.495 mm/mmHg. We constructed a nomogram depicting the TAPSE/PASP in conjunction with IL-6 and Lac for the joint prediction of sepsis prognosis, and demonstrated the highest predictive capability (AUC = 0.878, 95% CI 0.809–0.948). In conclusion, the TAPSE/PASP ratio demonstrated prognostic value for ICU mortality in sepsis patients. The nomogram, which combines the TAPSE/PASP, IL-6, and LAC, demonstrated enhanced predictive efficacy for the prognosis of sepsis patients.

Abstract Wide-scale sensing of natural and human-made events is critical for protecting against environmental disasters and reducing the monetary losses associated with telecommunication service downtime. However, achieving dense sensing coverage is difficult, given the high deployment overhead of modern sensor networks. Here we offer an in-depth exploration of state-of-polarization sensing over fiber-optic networks using unmodified optical transceivers to establish a strong correlation with ground truth distributed acoustic sensing. To validate our sensing methodology, we collect 85 days of polarization and distributed acoustic sensing measurements along two colocated, 50 km fiber-optic cables in Southern California. We then examine how polarization sensing can improve network reliability by accurately modeling overall network health and preemptively detecting traffic loss. Finally, we explore the feasibility of wide-scale seismic monitoring with polarization sensing, showcasing the polarization perturbations following low-intensity earthquakes and the potential to more than double seismic monitoring coverage in Southern California alone.

Gynostemma pentaphyllum (Thunb.) Makino (GP), a plant with homology of medicine and food, as a traditional Chinese medicine, possesses promising biological activities in the prevention and treatment of type 2 diabetes mellitus (T2DM). However, the material basis and the mechanism of action of GP in the treatment of T2DM have not been fully elucidated. This study aimed to clarify the active components, potential targets and signaling pathways of GP in treating T2DM. The chemical ingredients of GP were collected by combining UPLC-HRMS analysis and literature research. Network pharmacology revealed that GP had 32 components and 326 potential targets in treating T2DM. The results showed that GP affected T2DM by mediating the insulin resistance signaling pathway, PI3K/Akt signaling pathway and FoxO1 signaling pathway, which had a close relationship with T2DM. Molecular docking results showed that STAT3, PIK3CA, AKT1, EGFR, VEGFA and INSR had high affinity with the active compounds of GP. In vitro, GP extracts obviously increased the glucose uptake and glucose consumption in IR-HepG2 cells. GP extracts increased the levels of PI3K, p-AKT, p-GSK3β and p-FoxO1 and decreased the expression of p-IRS1, p-GS, PEPCK and G6Pase, which indicated that GP could promote glycogen synthesis and inhibit gluconeogenesis by regulating the IRS1/PI3K/Akt signaling pathway. The results demonstrated that GP could improve insulin resistance by promoting glucose uptake and glycogen synthesis and inhibiting gluconeogenesis through regulating the IRS1/PI3K/Akt signaling pathway, which might be a potential alternative therapy for T2DM.

Abstract The term “geographical synthetic thinking” is taken from the latest Chinese version of the “Geography Curriculum Standards” (General High School 2017 edition, Compulsory Education 2022 edition) and is one of the four core competencies prioritized in the teaching of geography at the secondary-school level. This study proposes that using geographic subject mind maps improves students’ geographical synthetic thinking and develops a set of geographic subject mind map (GSMM) drawing standards for teachers and matching standards and suggestions for teaching applications. Seven geography teachers and their students from eight class sections in seven provinces and cities in China were recruited to participate in the study. The teachers taught students how to use geographic subject mind maps designed to develop students’ geographical synthetic thinking in the geography classroom. After 4–5 experimental lessons, the geographical synthetic thinking level of the 267 valid student participants showed a significant improvement, with a statistically significant difference between pretest and posttest scores. The teachers’ level of application of geographic subject mind maps in teaching was significantly and positively correlated with the students’ improvements in geographical synthetic thinking, demonstrating that the standardized use of geographic subject mind maps in accordance with teaching application standards can effectively improve students’ geographical synthetic thinking levels.

Abstract Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remolding and occlusion, leading to the elevated pulmonary arterial pressures, right ventricular hypertrophy, and eventual heart failure if left untreated. Understanding the molecular mechanisms underlying the development and progression of pulmonary hypertension (PH) is crucial for devising efficient therapeutic approaches for the disease. Lung homogenates were collected weekly and underwent RNA-sequencing in the monocrotaline (MCT)-induced PH rat model to explore genes associated with PH progression. Statistical analyses revealed 1038, 1244, and 3125 significantly altered genes (P log21.5) between control and MCT-exposed rats during the first, second, and third week, respectively. Pathway enrichment analyses revealed involvement of cell cycle and innate immune system for the upregulated genes, GPCR and VEGF signaling for the downregulated genes. Furthermore, qRT-PCR validated upregulation of representative genes associated with cell cycle including Cdc25c (cell division cycle 25C), Cdc45, Top2a (topoisomerase IIα), Ccna2 (cyclin A2) and Ccnb1 (cyclin B1). Western blot and immunofluorescence analysis confirmed increases in PCNA, Ccna2, Top2a, along with other proliferation markers in the lung tissue of MCT-treated rats. In summary, RNA sequencing data highlights the significance of cell proliferation in progression of rodent PH.

Against the backdrop of rapid global climate change, the frequency and severity of storm surges in coastal areas are increasing, particularly in tidal river segments that are affected by storm surges and upstream river flooding. Although existing storm surge models have introduced a variety of different boundary settings, the boundary conditions provided are limited and cannot meet the current generalization needs of complex hydraulic engineering projects in China. This study considered the Feiyun River Basin as the research subject and coupled the upstream hydrodynamic model IFMS with the oceanic storm surge model ADCIRC. By utilizing the strengths of both models, a flood evolution model for the estuarine tidal river segment was established, enabling the spatiotemporal simulation of tidal levels in the Feiyun River tidal segment. The model not only effectively considers the impact of storm surge propagation at the estuary on flood evolution in the tidal river segment, but also the effect of upstream river flooding on the area. The study first validated the model with Typhoon Meranti in 2016, where the simulation results showed a high degree of agreement with the observed data series and errors were within acceptable limits. Flood processes at the Ruian, Mayu, Bishan Liqiao, and Dongtou tidal stations during Typhoons Doksuri and Khanun were simulated. The results show that the peak flood errors at all four stations were below 0.30 m, with Nash coefficients >0.80, indicating the model's capability to accurately reflect tidal level fluctuations and effectively contribute to disaster prevention and mitigation efforts in estuarine tidal segments. Finally, the study analyzed the impact of the driving forces of the upstream and downstream boundaries on tidal level predictions at three stations (Ruian, Mayu, and Bishan Liqiao). It was concluded that, compared to Mayu and Bishan Liqiao stations, the influence of the upstream boundary on Ruian can essentially be ignored, suggesting that the error from the upstream boundary under the influence of Typhoon Khanun is negligible for predicting errors at Ruian. The degree of the impact of the downstream boundary fluctuations on the three stations, from largest to smallest, was Ruian, Bishan Liqiao, and Mayu. Compared to the changes in the upstream boundary, the downstream boundary had a greater overall impact on all three stations. Additionally, when the downstream boundary changed by the same magnitude, the variation in low tide levels showed a decreasing trend from downstream to upstream, whereas the variation in high tide levels, although following the same trend, did not show a significant difference between the three. In summary, compared to the upstream boundary, the downstream boundary had a greater impact on tidal-level predictions at the three stations. The result shows that the lower boundary has a greater impact on the tidal level forecasts at three stations compared to the upper boundary. The study not only provides a new method for tidal river flood simulation in coastal urbanized areas but also offers directions for improving model simulation accuracy through analysis.