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Abstract At present, most of the analyses or studies about inductive power transfer (IPT) with constant current (CC) output and constant voltage (CV) output are carried out without considering misalignment conditions or different gaps. An IPT system satisfying battery charging demand and anti‐misalignment requirements simultaneously is infrequent. This paper proposes a multi‐objective particle swarm optimization method of IPT reconfigurable topology to realize CC and CV modes at varying resistance conditions and wide coupling ranges. The output characteristics of an inductor–capacitor–capacitor (LCC)–LCC compensation circuit have been explored, and it is found that the secondary‐side compensated capacitors have a greater impact on the output power, which can be used to improve power regulation ability accompanied by coupling varying. Eight optimization compensated parameters of the reconfigurable topology are obtained from the Pareto front to achieve the required CC and CV charging outputs. By switching the compensated capacitors, the selected parameters can make the current and voltage fluctuation less than 9.3% and 7.9%, respectively, during the coupling charging range from 0.3 to 0.22. Moreover, primary zero voltage switching operation is achieved to enable high efficiency. The simulation and the experimental verification are carried out to verify the validity of the proposed method.

Abstract Background Sepsis-induced myocardial dysfunction (SIMD) may contribute to the poor prognosis of septic patients. Carvacrol (2-methyl-5-isopropyl phenol), a phenolic monoterpene compound extracted from various aromatic plants and fragrance essential oils, has multiple beneficial effects such as antibacterial, anti-inflammatory, and antioxidant properties. These attributes make it potentially useful for treating many diseases. This study aims to investigate the effects of CAR on LPS-induced myocardial dysfunction and explore the underlying mechanism. Results H9c2 cells were stimulated with 10 µg/ml LPS for 12 h, and c57BL/6 mice were intraperitoneally injected with 10 mg/kg LPS to establish a septic-myocardial injury model. Our results showed that CAR could improve cardiac function, significantly reduce serum levels of inflammatory cytokines (including TNF-α, IL-1β, and IL-6), decrease oxidative stress, and inhibit cardiomyocyte apoptosis in LPS-injured mice. Additionally, CAR significantly downregulated the expression of TLR4, MyD88, and NF-κB in LPS-injured mice and H9c2 cells. It also inhibited the upregulation of inflammasome components (such as NLRP3, GSDMD, and IL-1β) in H9c2 cells triggered by LPS. Conclusion Taken together, CAR exhibited potential cardioprotective effects against sepsis, which may be mainly attributed to the TLR4/MyD88/NF-κB pathway and the NLRP3 inflammasome.

Abstract Background Antimicrobial resistance and bacterial hypermucoviscosity, associated with escalating production of capsules, constitute major challenges for the clinical management of Klebsiella pneumoniae (K. pneumoniae) infections. This study investigates the association and underlying mechanism between ceftazidime-avibactam (CAZ-AVI) resistance and bacterial hypermucoviscosity in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp). Results The proportion of CAZ-AVI-sensitive clinical isolates exhibiting the hypermucoviscous phenotype was significantly lower than that of the resistant strains (5.6% vs. 46.7%, P

Abstract Background The hyperinflammatory condition and lymphoproliferation due to Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) affect the detection of lymphomas by 18F-FDG PET/CT. We aimed to improve the diagnostic capabilities of 18F-FDG PET/CT by combining laboratory parameters. Methods This retrospective study involved 46 patients diagnosed with EBV-positive HLH, who underwent 18F-FDG PET/CT before beginning chemotherapy within a 4-year timeframe. These patients were categorized into two groups: EBV-associated HLH (EBV-HLH) (n = 31) and EBV-positive lymphoma-associated HLH (EBV + LA-HLH) (n = 15). We employed multivariable logistic regression and regression tree analysis to develop diagnostic models and assessed their efficacy in diagnosis and prognosis. Results A nomogram combining the SUVmax ratio, copies of plasma EBV-DNA, and IFN-γ reached 100% sensitivity and 81.8% specificity, with an AUC of 0.926 (95%CI, 0.779–0.988). Importantly, this nomogram also demonstrated predictive power for mortality in EBV-HLH patients, with a hazard ratio of 4.2 (95%CI, 1.1–16.5). The high-risk EBV-HLH patients identified by the nomogram had a similarly unfavorable prognosis as patients with lymphoma. Conclusions The study found that while 18F-FDG PET/CT alone has limitations in differentiating between lymphoma and EBV-HLH in patients with active EBV infection, the integration of a nomogram significantly improves the diagnostic accuracy and also exhibits a strong association with prognostic outcomes.

Abstract Introduction The estimated dose of radiation to immune cells (EDRIC) has been shown to correlate with the overall survival (OS) of patients who receive definitive thoracic radiotherapy. However, the planning target volume (PTV) may be a confounding factor. We assessed the prognostic value of EDRIC for non-small cell lung cancer (NSCLC) in patients who underwent postoperative radiotherapy (PORT) with homogeneous PTV. Methods Patients with NSCLC who underwent PORT between 2004 and 2019 were included. EDRIC was computed as a function of the number of radiation fractions and mean doses to the lungs, heart, and remaining body. The correlations between EDRIC and OS, disease-free survival (DFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using univariate and multivariate Cox models. Kaplan–Meier analysis was performed to assess the survival difference between low- and high-EDRIC groups. Results In total, 345 patients were analyzed. The mean EDRIC was 6.26 Gy. Multivariate analysis showed that higher EDRIC was associated with worse outcomes in terms of OS (hazard ratio [HR] 1.207, P = .007), DFS (HR 1.129, P = .015), LRFS (HR 1.211, P = .002), and DMFS (HR 1.131, P = .057). In the low- and high-EDRIC groups, the 3-year OS was 81.2% and 74.0%, DFS 39.8% and 35.0%, LRFS 70.4% and 60.5%, and DMFS 73.9% and 63.1%, respectively. Conclusions EDRIC is an independent prognostic factor for survival in patients with NSCLC undergoing PORT. Higher doses of radiation to the immune system are associated with tumor progression and poor survival. Organs at risk for the immune system should be considered during radiotherapy planning.

Developing a feasible and low-cost strategy for the recovery of calcium fluoride efficiently from fluoride-containing wastewater is very essential for the recycle of fluoride resources. Herein, a modified lime precipitation method was employed to recover CaF2 from fluorinated wastewater using a special icy lime solution. Intriguingly, the highest F– removal was greater than 95% under the optimal condition, leaving a fluoride concentration from 200 to 8.64 mg/L, while the lime dosage was much lower than that of industry. Importantly, spherical-shaped CaF2 particles with a 93.47% purity and size smaller than 600 nm were recovered, which has a high potential for the production of hydrofluoric acid. Besides, the precipitation was significantly affected by Ca/F molar ratio, stirring time, temperature, and solution pH. Furthermore, the thermodynamics and kinetics were investigated in detail to reveal the crystallization process. As a result, the defluorination reaction followed the pseudo-second order reaction kinetics model. Also, CO2 in the air adversely influenced the CaF2 purity. Based on this facile method, a high lime utilization efficiency was applied to defluorination, which contributed to protecting the environment and saving costs. This study, therefore, provides a feasible approach for the green recovery of fluorine resources and has significance for related research. HIGHLIGHTS A facile icy lime precipitation method was employed to remove F−.; Highly pure spherical particles with CaF2 of more than 93% were recovered.; Thermodynamics implied that CO2 had an inhibitory effect on the purity of CaF2.; Change in F fitted well with the pseudo-second order reaction kinetics model.; The co-precipitation of CaF2 and CaCO3 occurred.;

Abstract This study assessed the knowledge, attitude, and practice (KAP) of non-ophthalmic medical staff towards myopia-related fundus lesions. This multicenter, cross-sectional study enrolled non-ophthalmic medical staff of Suining City between January and May 2023 using a self-designed questionnaire. A total of 505 (93.19%) valid questionnaires were included. Their mean KAP scores were 8.10 ± 2.32 (range: 0–12), 20.27 ± 2.68 (range: 0–24), and 17.77 ± 5.04 (range: 0–28), respectively. Structural equation modeling indicated that knowledge has a positive effect on attitude (β = 0.307, P

Abstract Background Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Method First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy. Results The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978–0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response. Conclusion These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.

Abstract Background Because spontaneous remission is common in IMN, and there are adverse effects of immunosuppressive therapy, it is important to assess the risk of progressive loss of renal function before deciding whether and when to initiate immunosuppressive therapy. Therefore, this study aimed to establish a risk prediction model to predict patient prognosis and treatment response to help clinicians evaluate patient prognosis and decide on the best treatment regimen. Methods From September 2019 to December 2020, a total of 232 newly diagnosed IMN patients from three hospitals in Liaoning Province were enrolled. Logistic regression analysis selected the risk factors affecting the prognosis, and a dynamic online nomogram prognostic model was constructed based on extreme gradient boost, random forest, logistic regression machine learning algorithms. Receiver operating characteristic and calibration curves and decision curve analysis were utilized to assess the performance and clinical utility of the developed model. Results A total of 130 patients were in the training cohort and 102 patients in the validation cohort. Logistic regression analysis identified four risk factors: course ≥ 6 months, UTP, D-dimer and sPLA2R-Ab. The random forest algorithm showed the best performance with the highest AUROC (0.869). The nomogram had excellent discrimination ability, calibration ability and clinical practicability in both the training cohort and the validation cohort. Conclusions The dynamic online nomogram model can effectively assess the prognosis and treatment response of IMN patients. This will help clinicians assess the patient’s prognosis more accurately, communicate with the patient in advance, and jointly select the most appropriate treatment plan.

Abstract The prevalence of papillary thyroid cancer (PTC) has been rising in recent years. Despite its relatively low mortality, PTC frequently metastasizes to lymph nodes and often recurs, posing significant health and economic burdens. The role of iodine in the pathogenesis and advancement of thyroid cancer remains poorly understood. Circular RNAs (circRNAs) are recognized to function as competing endogenous RNAs (ceRNAs) that modulate gene expression and play a role in various cancer stages. Consequently, this research aimed to elucidate the mechanism by which circRNA influences the impact of iodine on PTC. Our research indicates that high iodine levels can exacerbate the malignancy of PTC via the circ_0004851/miR-296-3p/FGF11 axis. These insights into iodine’s biological role in PTC and the association of circRNA with the disease could pave the way for novel biomarkers and potentially effective therapeutic strategies to mitigate PTC progression.

Abstract Background Neuroblastoma (NB) is a highly heterogeneous tumor, and more than half of newly diagnosed NB are associated with extensive metastases. Accurately characterizing the heterogeneity of whole-body tumor lesions remains clinical challenge. This study aims to quantify whole-tumoral metabolic heterogeneity (WMH) derived from whole-body tumor lesions, and investigate the prognostic value of WMH in NB. Methods We retrospectively enrolled 95 newly diagnosed pediatric NB patients in our department. Traditional semi-quantitative PET/CT parameters including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. These PET/CT parameters were expressed as PSUVmax, PSUVmean, PSUVpeak, PMTV, PTLG for primary tumor, WSUVmax, WSUVmean, WSUVpeak, WMTV, WTLG for whole-body tumor lesions. The metabolic heterogeneity was quantified using the areas under the curve of the cumulative SUV-volume histogram index (AUC-CSH index). Intra-tumoral metabolic heterogeneity (IMH) and WMH were extracted from primary tumor and whole-body tumor lesions, respectively. The outcome endpoints were overall survival (OS) and progression-free survival (PFS). Survival analysis was performed utilizing the univariate and multivariate Cox proportional hazards regression. The optimal cut-off values for metabolic parameters were obtained by receiver operating characteristic curve (ROC). Results During follow up, 27 (28.4%) patients died, 21 (22.1%) patients relapsed and 47 (49.5%) patients remained progression-free survival, with a median follow-up of 35.0 months. In survival analysis, WMTV and WTLG were independent indicators of PFS, and WMH was an independent risk factor of PFS and OS. However, IMH only showed association with PFS and OS. In addition to metabolic parameters, the International Neuroblastoma Staging System (INSS) was identified as an independent risk factor for PFS, and neuron-specific enolase (NSE) served as an independent predictor of OS. Conclusion WMH was an independent risk factor for PFS and OS, suggesting its potential as a novel prognostic marker for newly diagnosed NB patients.

Abstract Background Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary tract cancer (BTC). This study used metagenomics and metabolomics to identify characteristics of the gut microbiome and metabolites in immunotherapy-treated BTC and their potential as prognostic and predictive biomarkers. Methods This prospective cohort study enrolled 88 patients with BTC who received PD-1/PD-L1 inhibitors from November 2018 to May 2022. The microbiota and metabolites significantly enriched in different immunotherapy response groups were identified through metagenomics and LC-MS/MS. Associations between microbiota and metabolites, microbiota and clinical factors, and metabolites and clinical factors were explored. Results Significantly different bacteria and their metabolites were both identified in the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups. Of these, 20 bacteria and two metabolites were significantly associated with survival. Alistipes were positively correlated with survival, while Bacilli, Lactobacillales, and Pyrrolidine were negatively correlated with survival. Predictive models based on six bacteria, four metabolites, and the combination of three bacteria and two metabolites could all discriminated between patients in the DCB and NDB groups with high accuracy. Beta diversity between two groups was significantly different, and the composition varied with differences in the use of immunotherapy. Conclusions Patients with BTC receiving immunotherapy have specific alterations in the interactions between microbiota and metabolites. These findings suggest that gut microbiota and metabolites are potential prognostic and predictive biomarkers for clinical outcomes of anti-PD-1/PD-L1-treated BTC.

Abstract Introduction About 17–80% stroke survivors experience the deficit of upper limb function, which strongly influences their independence and quality of life. Robot-assisted training and functional electrical stimulation are commonly used interventions in the rehabilitation of hemiplegia upper extremities, while the effect of their combination remains unclear. The aim of this trial is to explore the effect of robot-assisted upper limb training combined with functional electrical stimulation, in terms of neuromuscular rehabilitation, compared with robot-assisted upper limb training alone. Methods Individuals (n = 60) with the first onset of stroke (more than 1 week and less than 1 year after stroke onset) will be considered in the recruitment of this single-blinded, three-arm randomized controlled trial. Participants will be allocated into three groups (robot-assisted training combined with functional electrical stimulation group, robot-assisted training group, and conventional rehabilitation therapies group) with a ratio of 1:1:1. All interventions will be executed for 45 min per session, one session per day, 5 sessions per week for 6 weeks. The neuromuscular function of the upper limb (Fugl-Meyer Assessment of upper extremity), ability of daily life (modified Barthel Index), pain (visual analogue scale), and quality of life (EQ-5D-5L) will be assessed at the baseline, at the end of this trial and after 3 months follow-up. Two-way repeated measures analysis of variance will be used to compare the outcomes if the data are normally distributed. Simple effects tests will be used for the further exploration of interaction effects by time and group. Scheirer-Ray-Hare test will be used if the data are not satisfied with normal distribution. Discussion We expect this three-arm randomized controlled trial to explore the effectiveness of robot-assisted training combined with functional electrical stimulation in improving post-stroke upper limb function compared with robot-assisted training alone. Trial registration Effect of upper limb robot on improving upper limb function after stroke, identifier: ChiCTR2300073279. Registered on 5 July 2023.

To obtain the ignition performance of an integrated inclined combustor, we perform an experimental study on the ignition performance of an inclined combustor under various ignition positions, inlet flow rates, and fuel air ratios (FARs). The experimental results reveal the following. 1) During ignition at I1, the inclined combustor presents the best ignition performance. 2) The forward propagation process of flame along the swirler's inclined direction easily realizes flame propagation, whereas the backward flame propagation process in the swirler's inclined direction is difficult to achieve; forward and backward flame propagations exhibit evident differences. 3) The diffusion propagation of swirl flames at the ignition head is the main means swirl flames are generated at the nonignition head. 4) During the ignition process, the combustion intensity increases with the increase in FAR and decreases with the increase in inlet flow rate. 5) The successful ignition time decreases with the increase in inlet flow rate and FAR.

Abstract Migraine exhibits a substantial prevalence worldwide. The current diagnostic criteria rests exclusively on clinical characteristics without any objective and reliable means. The calcitonin gene‐related peptide (CGRP), as a biomarker for distinguishing migraine, undergoes swift degradation, featuring a half‐life of under 10 min, which poses a significant challenge to the point‐of‐care testing of CGRP in clinical application. Here, a photonic crystal (PC)‐based biochip has been developed to detect CGRP via the fluorescence competition assay. The chip integrates the functionalities of fluorescence enhancement and hydrophilic–hydrophobic patterning enrichment, enabling rapid and sensitive detection of CGRP. After investigating the optimal enhancement distance of fluorescence near PCs, the chip allows CGRP detection using

Lentiviruses, with their high transduction efficiency and gene expression levels, are widely used as gene delivery vectors in the development of chimeric antigen receptor T cells (CAR-T) and other genetically modified cell therapies. Accurate determination of the lentiviral vector infectious titer is essential to ensure effective transduction and product consistency. In this study, we developed an efficient method for lentiviral vector titration based on digital droplet polymerase chain reaction (ddPCR) technology, enabling absolute quantification of the target gene. Benzonase treatment of non-transduced plasmids substantially shortened the experimental period, reducing cell culture duration from 10-14 days–3 days. The method was rigorously validated by assessing specificity, working range, limit of quantification, precision, accuracy, and robustness. This study demonstrates the feasibility of combining enzymatic digestion with ddPCR to quantify lentiviral vector infectious titer and provides a detailed and readily adaptable methodology for the scientific community.

Background Fetal arrhythmias frequently co-occur with congenital heart disease in fetuses. The peaks observed in M-mode fetal echocardiograms serve as pivotal diagnostic markers for fetal arrhythmias. However, speckles, artifacts, and noise pose notable challenges for accurate image analysis. While current deep learning networks mainly overlook cardiac cyclic information, this study concentrated on the integration of such features, leveraging contextual constraints derived from cardiac cyclical features to improve diagnostic accuracy. Methods This study proposed a novel deep learning architecture for diagnosing fetal arrhythmias. The architecture presented a loss function tailored to the cardiac cyclical information and formulated a diagnostic algorithm for classifying fetal arrhythmias. The training and validation processes utilized a dataset comprising 4440 patches gathered from 890 participants. Results Incorporating cyclic loss significantly enhanced the performance of deep learning networks in predicting peak points for diagnosing fetal arrhythmia, resulting in improvements ranging from 7.11% to 14.81% in F 1-score across different network combinations. Particularly noteworthy was the 18.2% improvement in the F 1-score for the low-quality group. Additionally, the precision of diagnosing fetal arrhythmia across four categories exhibited improvement, with an average improvement rate of 20.6%. Conclusion This study introduced a cyclic loss mechanism based on the cardiac cycle information. Comparative evaluations were conducted using baseline methods and state-of-the-art deep learning architectures with the fetal echocardiogram dataset. These evaluations demonstrated the proposed framework’s superior accuracy in diagnosing fetal arrhythmias. It is also crucial to note that further external testing is essential to assess the model’s generalizability and clinical value.

Although the pollution of trace elements has been extensively studied, there is still a lack of comprehensive understanding regarding accumulation of these elements in lake ecosystems within the Yellow River basin, specifically the effects of lacustrine groundwater discharge (LGD) on trace elements. This study investigated the distribution, sources, and toxicity risks associated with 20 target trace elements (i.e., Li, Sc, Ti, V, Mn, Cr, Co, Ni, Cu, Zn, Rb, Y, Mo, Sb, Ba, W, Tl, Pb, U and Sr) in lake water (LW), groundwater (GW), and river water (RW) influenced by the LGD process in lake Ulansuhai and lake Daihai. The natural source is the primary contributor of trace elements in both LW and GW within the two lake basins, while industrial discharge plays a secondary role. The average LGD fluxes in lake Ulansuhai and Daihai basins were 6.39 × 105 m3/d and 1.07 × 105 m3/d, respectively. Additionally, the trace element fluxes from LGD in lake Ulansuhai (mean of 106,659.37 g/d) exceeded those observed in lake Daihai (mean of 3236.57 g/d). The overall toxicity risk was found to be higher in lake Ulansuhai (LW (17.36) > RW (16.81) > GW (12.76)) compared to lake Daihai (GW (10.43) > LW (9.10) > RW (4.63)). As well as the toxicity levels of trace elements in lake Ulansuhai were elevated compared to Daihai, which can be attributed to the influenced of ion compositions and water nutrients. Among them, Ca2+, Mg2+, and SO42+ were identified as key ions impacting the toxicity of trace elements in lake Ulansuhai. These findings provide crucial insights for targeted monitoring and mitigation of trace element pollution in the Yellow River basin’s lake ecosystems.

PurposeThe body contour of patients with cervical cancer is prone to change between radiotherapy sessions. This study aimed to investigate the effect of body contour changes on the setup and dosimetric accuracy of radiotherapy.Methods15 patients with cervical cancer after surgery were randomly selected for retrospective analysis. The body contours on the once-per-week cone-beam computed tomography (CBCT) were registered to the planning CT (pCT) for subsequent evaluation. A body contour conformity index (CIbody) was defined to quantify the variation of body changes. The body volume measured by CBCT was collected, and its relative difference in reference with the first CBCT was calculated and denoted by ΔVn. The relative setup errors, denoted by ΔSELR, ΔSEAP, ΔSESI, and ΔSEvec for left–right, anterior–posterior, superior–inferior, and vectorial shifts, respectively, were defined as the difference in measured setup errors between the reference and following CBCTs. The planned dose was calculated on the basis of virtual CT generated from CBCT and pCT by altering the CT body contour to fit the body on CBCT without deformable registration. The correlations between body contour changes and relative setup errors as well as dosimetric parameters were evaluated using Spearman’s correlation coefficient rs.ResultsCIbody was found to be negatively correlated with the superior–inferior and vectorial relative setup errors ΔSESI (rs = −0.448, p = 0.001) and ΔSEvec (rs = −0.387, p = 0.002), and no significant correlation was found between relative setup errors and ΔVn. Moreover, ΔVn was negatively correlated with ΔD2 (rs = −0.829, p < 0.001), ΔD98 (rs = −0.797, p < 0.001), and ΔTVPIV (rs = −0.819, p < 0.001). ΔD2, ΔD98, and ΔTVPIV were negatively correlated with ΔVn (p < 0.005). No correlation was found for other examined dosimetric parameters.ConclusionThe body contour change of patients could be associated with the setup variability. The effect of body contour changes on dose distribution is minimal. The extent of body change could be used as a metric for radiation therapists to estimate the setup errors.

The Spike of SARS-CoV-2 recognizes a transmembrane protease, angiotensin-converting enzyme 2 (ACE2), on host cells to initiate infection. Soluble derivatives of ACE2, in which Spike affinity is enhanced and the protein is fused to Fc of an immunoglobulin, are potent decoy receptors that reduce disease in animal models of COVID-19. Mutations were introduced into an ACE2 decoy receptor, including adding custom N-glycosylation sites and a cavity-filling substitution together with Fc modifications, which increased the decoy’s catalytic activity and provided small to moderate enhancements of pharmacokinetics following intravenous and subcutaneous administration in humanized FcRn mice. Most prominently, sialylation of native glycans increases exposures by orders of magnitude, and the optimized decoy is therapeutically efficacious in a mouse COVID-19 model. Ultimately, an engineered and highly sialylated decoy receptor produced using methods suitable for manufacture of representative drug substance has high exposure with a 5- to 9-day half-life. Finally, peptide epitopes at mutated sites in the decoys generally have low binding to common HLA class II alleles and the predicted immunogenicity risk is low. Overall, glycosylation is a critical molecular attribute of ACE2 decoy receptors and modifications that combine tighter blocking of Spike with enhanced pharmacokinetics elevate this class of molecules as viable drug candidates.

The aim of this study was to observe the remission of primary membranous nephropathy (PMN) and evaluate the efficacy of tacrolimus (TAC) monotherapy for PMN in comparison with TAC combined with a low-dose glucocorticoid (GC) protocol (TAC + GC).

Abstract Rheumatoid arthritis (RA) is an autoimmune disease. Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility. However, accumulating evidence demonstrates that genetics also shape the gut microbiota. It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis (CIA), while the others are resistant to CIA. Here, we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice. C57BL/6J mice and healthy human individuals have enriched B. fragilis than DBA/1J mice and RA patients. Transplantation of B. fragilis prevents CIA in DBA/1J mice. We identify that B. fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate. Fibroblast-like synoviocytes (FLSs) in RA are activated to undergo tumor-like transformation. Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1, resulting in reduced FOXK1 stability, blocked interferon signaling and deactivation of RA-FLSs. We treat CIA mice with propionate and show that propionate attenuates CIA. Moreover, a combination of propionate with anti-TNF etanercept synergistically relieves CIA. These results suggest that B. fragilis or propionate could be an alternative or complementary approach to the current therapies.

Abstract Background The value of postoperative radiotherapy (PORT) for patients with non-small cell lung cancer (NSCLC) remains controversial. A subset of patients may benefit from PORT. We aimed to identify patients with NSCLC who could benefit from PORT. Methods Patients from cohorts 1 and 2 with pathological Tany N2 M0 NSCLC were included, as well as patients with non-metastatic NSCLC from cohorts 3 to 6. The radiomic prognostic index (RPI) was developed using radiomic texture features extracted from the primary lung nodule in preoperative chest CT scans in cohort 1 and validated in other cohorts. We employed a least absolute shrinkage and selection operator-Cox regularisation model for data dimension reduction, feature selection, and the construction of the RPI. We created a lymph-radiomic prognostic index (LRPI) by combining RPI and positive lymph node number (PLN). We compared the outcomes of patients who received PORT against those who did not in the subgroups determined by the LRPI. Results In total, 228, 1003, 144, 422, 19, and 21 patients were eligible in cohorts 1–6. RPI predicted overall survival (OS) in all six cohorts: cohort 1 (HR = 2.31, 95% CI: 1.18–4.52), cohort 2 (HR = 1.64, 95% CI: 1.26–2.14), cohort 3 (HR = 2.53, 95% CI: 1.45–4.3), cohort 4 (HR = 1.24, 95% CI: 1.01–1.52), cohort 5 (HR = 2.56, 95% CI: 0.73–9.02), cohort 6 (HR = 2.30, 95% CI: 0.53–10.03). LRPI predicted OS (C-index: 0.68, 95% CI: 0.60–0.75) better than the pT stage (C-index: 0.57, 95% CI: 0.50–0.63), pT + PLN (C-index: 0.58, 95% CI: 0.46–0.70), and RPI (C-index: 0.65, 95% CI: 0.54–0.75). The LRPI was used to categorize individuals into three risk groups; patients in the moderate-risk group benefited from PORT (HR = 0.60, 95% CI: 0.40–0.91; p = 0.02), while patients in the low-risk and high-risk groups did not. Conclusions We developed preoperative CT-based radiomic and lymph-radiomic prognostic indexes capable of predicting OS and the benefits of PORT for patients with NSCLC.

Abstract The Waveflex semi-rigid-dynamic-internal-fixation system shows good short-term effects in the treatment of lumbar degenerative diseases, but there are few long-term follow-up studies, especially for recovery of sagittal balance. Fifty patients with lumbar degenerative diseases treated from January 2016 to October 2017 were retrospectively analysed: 25 patients treated with Waveflex semi-rigid-dynamic-internal-fixation system (Waveflex group) and 25 patients treated with double-segment PLIF (PLIF group). Clinical efficacy was evaluated by Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI). Imaging data before surgery and at 3 months, 1 year, and 5 years postoperatively was used for imaging indicator assessment. Local disc degeneration of the cephalic adjacent segment (including disc height index (DHI), intervertebral foramen height (IFH), and range of motion (ROM)) and overall spinal motor function (including lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), and |PI-LL|) were analysed. Regarding clinical efficacy, comparison of VAS and ODI scores between the Waveflex and PLIF groups showed no significant preoperative or postoperative differences. The comparison of the objective imaging indicators showed no significant differences in the DHI, IFH, LL, |PI-LL|, and SS values between the Waveflex and PLIF groups preoperatively and 3 months postoperatively (P > 0.05). These values were significantly different at 1 and 5 years postoperatively (P

Abstract Efficient milk production in mammals confers evolutionary advantages by facilitating the transmission of energy from mother to offspring. However, the regulatory mechanism responsible for the gradual establishment of milk production efficiency in mammals, from marsupials to eutherians, remains elusive. Here, we find that mammary gland of the marsupial sugar glider contained milk components during adolescence, and that mammary gland development is less dynamically cyclic compared to that in placental mammals. Furthermore, fused in sarcoma (FUS) is found to be partially responsible for this establishment of low efficiency. In mouse model, FUS inhibit mammary epithelial cell differentiation through the cyclin-dependent kinase inhibitor p57Kip2, leading to lactation failure and pup starvation. Clinically, FUS levels are negatively correlated with milk production in lactating women. Overall, our results shed light on FUS as a negative regulator of milk production, providing a potential mechanism for the establishment of milk production from marsupial to eutherian mammals.

Abstract Background Solanum aculeatissimum and Solanum torvum belong to the Solanum species, and they are essential plants known for their high resistance to diseases and adverse conditions. They are frequently used as rootstocks for grafting and are often crossbred with other Solanum species to leverage their resistance traits. However, the phylogenetic relationship between S. aculeatissimum and S. torvum within the Solanum genus remains unclear. Therefore, this paper aims to sequence the complete chloroplast genomes of S. aculeatissimum and S. torvum and analyze them in comparison with 29 other previously published chloroplast genomes of Solanum species. Results We observed that the chloroplast genomes of S. aculeatissimum and S. torvum possess typical tetrameric structures, consisting of one Large Single Copy (LSC) region, two reverse-symmetric Inverted Repeats (IRs), and one Small Single Copy (SSC) region. The total length of these chloroplast genomes ranged from 154,942 to 156,004 bp, with minimal variation. The highest GC content was found in the IR region, while the lowest was in the SSC region. Regarding gene content, the total number of chloroplast genes and CDS genes remained relatively consistent, ranging from 128 to 134 and 83 to 91, respectively. Nevertheless, there was notable variability in the number of tRNA genes and rRNAs. Relative synonymous codon usage (RSCU) analysis revealed that both S. aculeatissimum and S. torvum preferred codons that utilized A and U bases. Analysis of the IR boundary regions indicated that contraction and expansion primarily occurred at the junction between SSC and IR regions. Nucleotide polymorphism analysis and structural variation analysis demonstrated that chloroplast variation in Solanum species mainly occurred in the LSC and SSC regions. Repeat sequence analysis revealed that A/T was the most frequent base pair in simple repeat sequences (SSR), while Palindromic and Forward repeats were more common in long sequence repeats (LSR), with Reverse and Complement repeats being less frequent. Phylogenetic analysis indicated that S. aculeatissimum and S. torvum belonged to the same meristem and were more closely related to Cultivated Eggplant. Conclusion These findings enhance our comprehension of chloroplast genomes within the Solanum genus, offering valuable insights for plant classification, evolutionary studies, and potential molecular markers for species identification.

Abstract Dietary salt has been associated with cognitive impairment in mice, possibly related to damaged synapses and tau hyperphosphorylation. However, the mechanism underlying how dietary salt causes cognitive dysfunction remains unclear. In our study, either a high-salt (8%) or normal diet (0.5%) was used to feed C57BL/6 mice for three months, and N2a cells were cultured in normal medium, NaCl medium (80 mM), or NaCl (80 mM) + Liraglutide (200 nM) medium for 48 h. Cognitive function in mice was assessed using the Morris water maze and shuttle box test, while anxiety was evaluated by the open field test (OPT). Western blotting (WB), immunofluorescence, and immunohistochemistry were utilized to assess the level of Glucagon-like Peptide-1 receptor (GLP-1R) and mTOR/p70S6K pathway. Electron microscope and western blotting were used to evaluate synapse function and tau phosphorylation. Our findings revealed that a high salt diet (HSD) reduced the level of synaptophysin (SYP) and postsynaptic density 95 (PSD95), resulting in significant synaptic damage. Additionally, hyperphosphorylation of tau at different sites was detected. The C57BL/6 mice showed significant impairment in learning and memory function compared to the control group, but HSD did not cause anxiety in the mice. In addition, the level of GLP-1R and autophagy flux decreased in the HSD group, while the level of mTOR/p70S6K was upregulated. Furthermore, liraglutide reversed the autophagy inhibition of N2a treated with NaCl. In summary, our study demonstrates that dietary salt inhibits the GLP-1R/mTOR/p70S6K pathway to inhibit autophagy and induces synaptic dysfunction and tau hyperphosphorylation, eventually impairing cognitive dysfunction.

Abstract Background The combination of rituximab and chemotherapy is a first-line treatment for patients with B-cell non-Hodgkin lymphoma. Lenalidomide is an immunomodulatory drug that has shown promising properties and activity in a variety of hematological malignancies. This study evaluated the efficacy and safety of lenalidomide-based regimens in the treatment of B-cell non-Hodgkin lymphoma. Methods The PubMed, Science Direct, ClinicalTrials.gov, and Web of Science databases were searched for relevant studies published up to May 2022. Studies with patients diagnosed with non-Hodgkin B-cell lymphoma, who were randomly assigned to a lenalidomide treatment group or a non-lenalidomide control group were considered for inclusion in this review and meta-analysis. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of the time-to-event outcomes and risk ratios (RRs) with 95% CIs of dichotomous data were estimated. Results A total of 3593 patients from 10 studies were evaluated. The results of the pooled analysis indicated that the lenalidomide-based regimen was associated with prolonged overall survival (HR, 0.85; 95% CI 0.74–0.97; P = 0.02) and progression-free survival (HR, 0.70; 95% CI 0.57–0.88; P = 0.002). Significant differences were found in the overall response rate (RR, 1.18; 95% CI 1.04–1.33; P = 0.01) and complete response rate (RR, 1.18; 95% CI 1.00–1.39; P = 0.05) between the treatment and control groups. Conclusions Lenalidomide appears to be a promising therapeutic agent that offers the possibility of a novel combination of chemotherapy free regimen for patients with B-cell non-Hodgkin lymphoma.

Detection of specific antinuclear antibodies is very important in term of diagnosis, prognosis and management of patients with systemic autoimmune rheumatic diseases. Chemiluminescence microarray immunoassay (CLMIA) is a microdot array-based method that allows simultaneous detection of multiple antinuclear antibodies, which received increasing attention.

Road transportation plays a crucial role in society and daily life, as the functioning and durability of roads can significantly impact a nation's economic development. In the whole life cycle of the road, the emergence of disease is unavoidable, so it is necessary to adopt relevant technical means to deal with the disease. This study comprehensively reviews the advancements in computer vision, artificial intelligence, and mobile robotics in the road domain and examines their progress and applications in road detection, diagnosis, and treatment, especially asphalt roads. Specifically, it analyzes the research progress in detecting and diagnosing surface and internal road distress and related techniques and algorithms are compared. In addition, also introduces various road governance technologies, including automated repairs, intelligent construction, and path planning for crack sealing. Despite their proven effectiveness in detecting road distress, analyzing diagnoses, and planning maintenance, these technologies still confront challenges in data collection, parameter optimization, model portability, system accuracy, robustness, and real-time performance. Consequently, the integration of multidisciplinary technologies is imperative to enable the development of an integrated approach that includes road detection, diagnosis, and treatment. This paper addresses the challenges of precise defect detection, condition assessment, and unmanned construction. At the same time, the efficiency of labor liberation and road maintenance is achieved, and the automation level of the road engineering industry is improved.

Abstract Modulation of protein function through allosteric regulation is central in biology, but biomacromolecular systems involving multiple subunits and ligands may exhibit complex regulatory mechanisms at different levels, which remain poorly understood. Here, we discover an aldo-keto reductase termed AKRtyl and present its three-level regulatory mechanism. Specifically, by combining steady-state and transient kinetics, X-ray crystallography and molecular dynamics simulation, we demonstrate that AKRtyl exhibits a positive synergy mediated by an unusual Monod-Wyman-Changeux (MWC) paradigm of allosteric regulation at low concentrations of the cofactor NADPH, but an inhibitory effect at high concentrations is observed. While the substrate tylosin binds at a remote allosteric site with positive cooperativity. We further reveal that these regulatory mechanisms are conserved in AKR12D subfamily, and that substrate cooperativity is common in AKRs across three kingdoms of life. This work provides an intriguing example for understanding complex allosteric regulatory networks.

Rockbursts have become one of the most serious hazards in underground mines worldwide. While the characteristics of ground motions before rockbursts (or high-magnitude events (HMEs)) have not been studied. In this study, the peak ground velocity (PGV) and cumulative absolute displacement (CAD) before HMEs were examined based on seismic monitoring in a coal mine. It’s found that the source mechanisms vary significantly across different zones of the longwall, attributed to the low correlation between rock fracture types, stress levels, and seismic intensity. This correlation is mainly related to the distribution of primary fractures within the rock mass. The non-overlap of CAD peak with HME and the induction of delayed rockbursts are mainly caused by the unavoidable creep and additional energy input into the coal mass under disturbances before instability. The energy conversion process of the entire system is determined to be controlled by the stiffness ratio between the roof-floor system and the loaded coal, in accordance with the concept of dynamic and static load superposition. A high static load, strong dynamic disturbances, and a low rigidity ratio between surrounding rock and coal are identified as the most hazardous factors.

Aims This study aims to explore the alterations of dendritic cells (DCs) subpopulations in ectopic endometrial lesions and unveil the underlying mechanisms.Materials and methods Patients with endometriosis (n = 81) and women without endometriosis (n = 19) were recruited in this study. Dendritic cells (DCs) in the endometrial samples were counted after immunohistochemistry staining. The proportion of myeloid DCs and plasmacytoid DCs was calculated by flow cytometry. Primary DCs were isolated from tissues, and the cell viability and apoptosis were examined by MTT assay and flow cytometry. Cytokines were detected by the enzyme-linked immunosorbent assay. Differentially expressed genes were filtered by analyzing two datasets that were downloaded from GEO database and detected by RT-qPCR in tissues and isolated DCs. The function of HSD11B1 was examined in an endometrial stromal cell-DCs co-culture system and in vitro cultured DCs.Results Reduced myeloid DCs and increased CD11c-CD304-DCs were found in ectopic endometrium compared to control endometrium and eutopic endometrium from endometriosis patients. Myeloid DCs isolated from ectopic endometrium expressed less CD80, CD83, CD86 and had reduced proliferation, increased apoptosis, and reduced cytokine production. The expression of HSD11B1 was significantly increased in both ectopic endometrium and isolated myeloid DCs. Overexpression of HSD11B1 in immature DCs could repress DCs maturation and cytokine production. Endometrial stromal cells overexpressing HSD11B1 secreted increased cortisol, which repressed DCs maturation.Conclusions HSD11B1 is upregulated in ectopic endometrial lesions, which may contribute to endometriosis through repressing myeloid DCs maturation.

ABSTRACTInterferometric Synthetic Aperture Radar (InSAR) is capable of detecting crust deformation. However, the accuracy is limited by spatiotemporal changes in the lower troposphere. In this paper, we constructed a periodic zenith total delay negative exponential function (PZTD-NEF) model of atmospheric spatiotemporal variation characteristics based on ERA-5 data to alleviate the temporal oscillation bias introduced by tropospheric delay and improve the accuracy of time series InSAR (TS-InSAR) inversion of surface deformation. We evaluated the model’s performance using the phase standard deviation (STD), atmospheric delay correlation coefficient with topography and the spatial structure function. The results were compared with a linear topography-dependent empirical model, generic atmospheric correction online service (GACOS) and ERA-5 methods. Our method reduces the STD of the phase of 83% of the interferograms by 12.8%. For vertical stratification delay correction, the correlation between the proposed method and the Linear, GACOS, and ERA-5 reached 0.734, 0.708, and 0.729, respectively. We found that accounting for spatiotemporal variation characteristics of tropospheric delay can alleviate the seasonal oscillations of vertical stratification delay and improve the accuracy of the deformation time series solution by 40.04%. We also used the Kunming continuous operation reference station system (KMCORS) to verify the displacement results of our method.

Background Inflammation plays a crucial role in occurrence of kidney injury, and specific dietary patterns can influence systemic inflammation levels. However, the relationship between dietary inflammatory potential and early-stage kidney damage remains unclear.Method 2,108 participants was recruited from 2001–2002 National Health and Nutrition Examination Survey (NHANES). Dietary Inflammatory Index (DII) is utilized to assess dietary inflammatory potential, calculated through a 24-h dietary recall questionnaire. Early renal injury was evaluated using urinary albumin to creatinine (UACR), cystatin C (CysC), β-2 microglobulin (β2M), and estimated glomerular filtration rate (eGFR) based on serum creatinine (eGFRs), cystatin C (eGFRc), and both Scr and CysC (eGFRs&c). Participant characteristics were analyzed, and association between DII, hypertension, and early renal injury markers was explored using multiple linear and logistic regression models.Results The average age of participants was 53.9 years. DII exhibited a positive correlation with UACR (β = −0.048[0.017,0.078]), β2M (β = 0.019[0.010,0.027]), CysC (β = 0.012 [0.004,0.021]). Conversely, a negative correlation was observed between DII and eGFRc (β = −1.126[−1.554, −0.699]), eGFRs&c (β=-1.101[−1.653, −0.549]). A significant association was observed between hypertension and abnormality of early kidney damage markers. Subgroup analysis reveals that the positive correlation between DII and the occurrence of abnormal markers of early kidney damage is only observed in individuals with hypertension. Furthermore, an interaction between DII and hypertension was detected in eGFRs&c (OR:1.250[1.042, 1.499], p for interaction = 0.03).Conclusion Higher levels of DII may be associated with occurrence of early kidney damage. For individuals with hypertension, avoiding excessive consumption of pro-inflammatory foods may reduce the risk of renal injury.

IntroductionThe occurrence of Spinal cord injury (SCI) brings economic burden and social burden to individuals, families and society, and the complications after SCI greatly affect the rehabilitation and treatment of patients in the later stage.This study focused on the potential biomarkers that co-exist in SCI and sarcopenia, with the expectation to diagnose and prognose patients in the acute phase and rehabilitation phase using comprehensive data analysis.MethodsThe datasets used in this study were downloaded from Gene Expression Omnibus (GEO) database. Firstly, the datasets were analyzed with the “DEseq2” and “Limma” R package to identify differentially expressed genes (DEGs), which were then visualized using volcano plots. The SCI and sarcopenia DEGs that overlapped were used to construct a protein–protein interaction (PPI) network. Three algorithms were used to obtain a list of the top 10 hub genes. Next, validation of the hub genes was performed using three datasets. According to the results, the top hub genes were DCN, FSTL1, and COL12A1, which subsequently underwent were Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. We also assessed immune cell infiltration with the CIBERSORT algorithm to explore the immune cell landscape. The correlations between the hub genes and age and body mass index were investigated. To illustrate the biological mechanisms of the hub genes more clearly, a single-cell RNA-seq dataset was assessed to determine gene expression when muscle injury occurred. According to our analysis and the role in muscle, we chose the fibro/adipogenic progenitors (FAPs) cluster in the next step of the analysis. In the sub cluster analysis, we use the “Monocle” package to perform the trajectory analysis in different injury time points and different cell states.ResultsA total of 144 overlapped genes were obtained from two datasets. Following PPI network analysis and validation, we finally identified three hub-genes (DCN, FSTL1, and COL12A1), which were significantly altered in sarcopenic SCI patients both before and after rehabilitation training. The three hub genes were also significantly expressed in the FAPs clusters. Furthermore, following injury, the expression of the hub genes changed with the time points, changing in FAPs cluster.DiscussionOur study provides comprehensive insights into how muscle changes after SCI are associated with sarcopenia by moving from RNA-seq to RNA-SEQ, including Immune infiltration landscape, pesudotime change and so on. The three hub genes identified in this study could be used to distinguish the sarcopenia state at the genomic level. Additionally, they may also play a prognostic role in evaluating the efficiency of rehabilitation training.

Abstract All‐solid‐state batteries equipped with solid‐state electrolytes (SSEs) have gained significant interest due to their enhanced safety, energy density, and longevity in comparison to traditional liquid organic electrolyte‐based batteries. However, many SSEs, such as sulfides and hydrides, are highly sensitive to water, limiting their practical use. As one class of important perovskites, the Ruddlesden–Popper perovskite oxides (RPPOs), show great promise as SSEs due to their exceptional stability, particularly in terms of water resistance. In this review, the crystal structure and synthesis methods of RPPOs SSEs are first introduced in brief. Subsequently, the mechanisms of ion transportation, including oxygen anions and lithium‐ions, and the relevant strategies for enhancing their ionic conductivity are described in detail. Additionally, the progress made in developing flexible RPPOs SSEs, which are critical for flexible and wearable electronic devices, has also been summarized. Furthermore, the key challenges and prospects for exploring and developing RPPOs SSEs in all‐solid‐state batteries are suggested. This review presents in detail the synthesis methods, the ion transportation mechanism, and strategies to enhance the room temperature ionic conductivity of RPPOs SSEs, providing valuable insights on enhancing their ionic conductivity and thus for their practical application in solid‐state batteries.

ObjectivesDepressive symptoms are the most prevalent comorbidity in individuals with obsessive-compulsive disorder (OCD). The objective of this study was to investigate the dynamic characteristics of resting-state neural activities in OCD patients with depressive symptoms.MethodsWe recruited 29 OCD patients with depressive symptoms, 21 OCD patients without depressive symptoms, and 27 healthy controls, and collected data via structural and functional magnetic resonance imaging (fMRI). We analyzed the fMRI results using the dynamic amplitude of low-frequency fluctuation (dALFF) and support vector machine (SVM) techniques.ResultsCompared with OCD patients without depressive symptoms, OCD patients with depressive symptoms exhibited an increased dALFF in the left precuneus and decreased dALFF in the right medial frontal gyrus. The SVM indicated that the integration of aberrant dALFF values in the left precuneus and right medial frontal gyrus led to an overall accuracy of 80%, a sensitivity of 79%, and a specificity of 100% in detecting depressive symptoms among OCD patients.ConclusionTherefore, our study reveals that OCD patients with depressive symptoms display neural activities with unique dynamic characteristics in the resting state. Accordingly, abnormal dALFF values in the left precuneus and right medial frontal gyrus could be used to identify depressive symptoms in OCD patients.

Summary: Sensory and emotional experiences are essential for mental and physical well-being, especially within the realm of psychiatry. This article highlights recent advances in cognitive neuroscience, emphasizing the significance of pain recognition and empathic artificial intelligence (AI) in healthcare. We provide an overview of the recent development process in computational pain recognition and cognitive neuroscience regarding the mechanisms of pain and empathy. Through a comprehensive discussion, the article delves into critical questions such as the methodologies for AI in recognizing pain from diverse sources of information, the necessity for AI to exhibit empathic responses, and the associated advantages and obstacles linked with the development of empathic AI. Moreover, insights into the prospects and challenges are emphasized in relation to fostering artificial empathy. By delineating potential pathways for future research, the article aims to contribute to developing effective assistants equipped with empathic capabilities, thereby introducing safe and meaningful interactions between humans and AI, particularly in the context of mental health and psychiatry.

T-2 toxin is one of trichothecene mycotoxins, which can impair appetite and decrease food intake. However, the specific mechanisms for T-2 toxin-induced anorexia are not fully clarified. Multiple research results had shown that gut microbiota have a significant effect on appetite regulation. Hence, this study purposed to explore the potential interactions of the gut microbiota and appetite regulate factors in anorexia induced by T-2 toxin. The study divided the mice into control group (CG, 0 mg/kg BW T-2 toxin) and T-2 toxin-treated group (TG, 1 mg/kg BW T-2 toxin), which oral gavage for 4 weeks, to construct a subacute T-2 toxin poisoning mouse model. This data proved that T-2 toxin was able to induce an anorexia in mice by increased the contents of gastrointestinal hormones (CCK, GIP, GLP-1 and PYY), neurotransmitters (5-HT and SP), as well as pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in serum of mice. T-2 toxin disturbed the composition of gut microbiota, especially, Faecalibaculum and Allobaculum, which was positively correlated with CCK, GLP-1, 5-HT, IL-1β, IL-6 and TNF-α, which played a certain role in regulating host appetite. In conclusion, gut microbiota changes (especially an increase in the abundance of Faecalibaculum and Allobaculum) promote the upregulation of gastrointestinal hormones, neurotransmitters, and pro-inflammatory cytokines, which may be a potential mechanism of T-2 toxin-induced anorexia.

Abstract Ferroptosis plays important roles both in normal physiology and multiple human diseases. It is well known that selenoprotein named glutathione peroxidase 4 (GPX4) is a crucial regulator for ferroptosis. However, it remains unknown whether other selenoproteins responsible for the regulation of ferroptosis, particularly in gut diseases. In this study, it is observed that Selenoprotein I (Selenoi) prevents ferroptosis by maintaining ether lipids homeostasis. Specific deletion of Selenoi in intestinal epithelial cells induced the occurrence of ferroptosis, leading to impaired intestinal regeneration and compromised colonic tumor growth. Mechanistically, Selenoi deficiency causes a remarkable decrease in ether‐linked phosphatidylethanolamine (ePE) and a marked increase in ether‐linked phosphatidylcholine (ePC). The imbalance of ePE and ePC results in the upregulation of phospholipase A2, group IIA (Pla2g2a) and group V (Pla2g5), as well as arachidonate‐15‐lipoxygenase (Alox15), which give rise to excessive lipid peroxidation. Knockdown of PLA2G2A, PLA2G5, or ALOX15 can reverse the ferroptosis phenotypes, suggesting that they are downstream effectors of SELENOI. Strikingly, GPX4 overexpression cannot rescue the ferroptosis phenotypes of SELENOI‐knockdown cells, while SELENOI overexpression can partially rescue GPX4‐knockdown‐induced ferroptosis. It suggests that SELENOI prevents ferroptosis independent of GPX4. Taken together, these findings strongly support the notion that SELENOI functions as a novel suppressor of ferroptosis during colitis and colon tumorigenesis.

In recent years, non-point source pollution (NPSP) has become prominent in the Yellow River Basin (YRB) of China and seriously affects human survival and sustainable development. The Henan section was selected as an example region of the YRB in China, and the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model has been used to quantitatively evaluate nitrogen (N) and phosphorus (P). The results show that (1) the cultivated land (CL), grassland (GL), and unused land (UL) decreased, while forest land (FL), water areas (WAs), and built-up areas (BAs) increased in 2000–2020, and precipitation increased from the northeast to the southwest in 2000–2020; (2) the N export was much more than P export in 2000, 2010, and 2020, and the N and P exports increased in 2000–2020; the spatial distribution of N and P export changes was different in the whole basin in 2000–2010, 2010–2020, and 2000–2020; (3) the N and P exports decreased in 2000–2010, 2010–2020, and 2000–2020 with increasing precipitation; and (4) the N and P exports on CL and BAs were more than those on the other land-use types, and the overall change trends of N and P exports on all land-use types increased from 2000 to 2020.

In the process of ascending and descending in deep-sea submerging and lifting cage nets, accompanied by changes in water pressure, pressure is one of the crucial environmental factors affecting the physiology and growth of fish. It directly relates to the comfort of farmed fish in the cage, thereby influencing the quality of aquaculture, especially for high-demanding species on the culture environment like the Larimichthys crocea. Investigating the stress level changes exhibited by L.crocea under environmental pressure variations, understanding the limit tolerance pressure, and its changes, can provide a theoretical basis for the design, application, and increased production of deep-sea submersible cage nets and L.crocea aquaculture. This study explores the effects of varying submersion depths (0–20 m) and speeds (0.6, 1, 1.3, 2, 4 m/min) on the behavioral responses of L.crocea in deep-sea cage environments. Key findings demonstrate that increased submersion depths and speeds significantly influence the physical behaviors and stress responses of the species. At submersion depths of 15 meters and 20 meters, the average swimming speed of the L.crocea exceeds 0.05 meters per second, the tail movement frequency is 1.42 times that of normal pressure, and the gasping frequency exceeds 20%., and at the highest speed of 4 m/min, the swimming speed reaches 0.0902 m/s—3.76 times greater than under normal pressure. The study determines that a submersion depth of 10 meters and a submersion speed of 0.6 meters per minute can minimize stress responses, providing critical insights for optimizing deep-sea aquaculture operations of L.crocea. These results offer valuable guidelines for the design and management of submersible cage systems.

IntroductionThis study aims to investigate whether the transrectal ultrasound-guided combined biopsy (CB) improves the detection rates of prostate cancer (PCa) and clinically significant PCa (csPCa) in biopsy-naïve patients. We also aimed to compare the Prostate Imaging Reporting and Data System (PI-RADS v2.1) score, ADC values, and PSA density (PSAd) in predicting csPCa by the combined prostate biopsy.MethodsThis retrospective and single-center study included 389 biopsy-naïve patients with PSA level 4~20 ng/ml, of whom 197 underwent prebiopsy mpMRI of the prostate. The mpMRI-based scores (PI-RADS v2.1 scores and ADC values) and clinical parameters were collected and evaluated by logistic regression analyses. Multivariable models based on the mpMRI-based scores and clinical parameters were developed by the logistic regression analyses to forecast biopsy outcomes of CB in biopsy-naïve patients. The ROC curves measured by the AUC values, calibration plots, and DCA were performed to assess multivariable models.ResultsThe CB can detect more csPCa compared with TRUSB (32.0% vs. 53%). The Spearman correlation revealed that Gleason scores of the prostate biopsy significantly correlated with PI-RADS scores and ADC values. The multivariate logistic regression confirmed that PI-RADS scores 4, 5, and prostate volume were important predictors of csPCa. The PI-RADS+ADC+PSAd (PAP) model had the highest AUCs of 0.913 for predicting csPCa in biopsy-naïve patients with PSA level 4~20 ng/ml. When the biopsy risk threshold of the PAP model was greater than or equal to 0.10, 51% of patients could avoid an unnecessary biopsy, and only 5% of patients with csPCa were missed.ConclusionThe prebiopsy mpMRI and the combined prostate biopsy have a high CDR of csPCa in biopsy-naïve patients. A multivariable model based on the mpMRI-based scores and PSAd could provide a reference for clinicians in forecasting biopsy outcomes in biopsy-naïve patients with PSA 4~20 ng/ml and make a more comprehensive assessment during the decision-making of the prostate biopsy.

Given the expanding global population and finite resources, it is imperative to explore alternative technologies for food production. These technologies play a crucial role in ensuring the provision of safe, nutritious, and sustainable food options to meet the growing demand. Cellular agriculture plays an important in developing an alternative method for developing food products. While, cellular agriculture is emerging rapidly, food safety aspects and regulatory frameworks stayed behind. Despite developing several regulatory framework papers on cellular agriculture, there is no systematic approach for developing a comprehensive food safety plan (FSP), particularly for cultivated seafood. Thus, the overall goal of this article is to develop a FSP for cultivated seafood. The main differences between the food safety plan for cultivated seafood and the conventional seafood industries were the number of allergens in cultivated seafood products, including soy, wheat, and fish cells, compared to only fish for the conventional seafood industry. In addition, there are several hazards associated with mycoplasma in cultivated seafood, which should be considered. This guidance intends to help regulatory agencies, food safety experts, startup companies, and the cultivated seafood industry by providing a valuable platform to develop regulations, guidance, and food safety plans applicable to most cultivated seafood companies. This article will also help the industry to identify the hazards in their processing line and develop preventive controls, and as a comprehensive food safety plan, it could be easily adapted for other cultivated seafood products. This guidance applied systematic approaches to developing food safety plans using cell culture, pharmaceuticals, fermentation, seafood, meat, and aquaponics safety plans, collaborating with experts with different backgrounds, and working closely with the conventional and cultivated meat and seafood industries.

The advancement of convolutional neural networks (CNNs) has markedly progressed in the field of face detection, significantly enhancing accuracy and recall metrics. Precision and recall remain pivotal for evaluating CNN-based detection models; however, there is a prevalent inclination to focus on improving true positive rates at the expense of addressing false positives. A critical issue contributing to this discrepancy is the lack of pseudo-face images within training and evaluation datasets. This deficiency impairs the regression capabilities of detection models, leading to numerous erroneous detections and inadequate localization. To address this gap, we introduce the WIDERFACE dataset, enriched with a considerable number of pseudo-face images created by amalgamating human and animal facial features. This dataset aims to bolster the detection of false positives during training phases. Furthermore, we propose a new face detection architecture that incorporates a classification model into the conventional face detection model to diminish the false positive rate and augment detection precision. Our comparative analysis on the WIDERFACE and other renowned datasets reveals that our architecture secures a lower false positive rate while preserving the true positive rate in comparison to existing top-tier face detection models.

Switching wells in high-temperature and high-pressure gas wells will affect parameters such as the temperature and pressure of the fluid in the wellbore. Dynamic monitoring of temperature and pressure is difficult, and wellbore temperature, pressure, and fluid physical parameters are coupled to each other. Obtaining them separately will lead to large calculation errors. In order to improve the prediction accuracy of temperature and pressure in high-temperature and high-pressure gas wells, Based on the temperature–pressure coupling algorithm, this study compares the advantages and disadvantages of nine classic algorithms based on the temperature–pressure coupling algorithm, considers the impact of high temperature and high pressure on the temperature and pressure of the gas wellbore fluid, and establishes an unsteady temperature–pressure coupling model for high-temperature and high-pressure gas wells under on–off well conditions. Comparing with the measured data, it is proved that the prediction accuracy of the unsteady temperature–pressure coupling model of high-temperature and high-pressure gas wells meets the construction requirements of switch wells. The established model is used to simulate the temperature and pressure distribution of two high-temperature and high-pressure gas wells under switching conditions. The analysis shows that the distribution of wellbore temperature and pressure under the switch on and off conditions is affected by the gas–water ratio, heat transfer coefficient, tube size, and gas well production. Among them, the gas–water ratio increased by 1.5 times, the wellhead temperature increased by 25%, and the wellhead pressure decreased is 7.68%; When the heat transfer coefficient is increased by 1.5 times, the wellhead temperature drops to 34.38% and the wellhead pressure drops to 2.29%. When the tube size is increased by 1.125 times, the wellhead temperature is reduced by 44.20% and the pressure is increased by 6.09%. When the production of gas well is doubled, the wellhead temperature increases by 40.79% and the wellhead pressure decreases by 2.29%. The results can be used as a basis for the construction of high-temperature and high-pressure gas wells.

Typically, parasitic capacitances exist between the ground and the solar panel terminals in grid-connected PV systems. These parasitic capacitances provide a path for a leakage current, which leads to significant safety concerns, observable and seriously hazardous harmonic orders aligned with the injected grid current, and significant safety difficulties. In this research, a robust PWM controlling method that used competently in reducing the level of the leakage current and improving the power quality of a switched-capacitor Multilevel Inverter. This technique creates developed reference signals from the main signal to generate the switching scheme for the converter circuit. Additionally, the suggested control strategy only works with a small number of carrier signals, resulting in a quick system response and a simpler controller algorithm. Likewise, this controlling approach offers a stable way to maintain a constant output voltage in the suggested converter by adjusting the switching capacitors' voltages, which is not possible with traditional control techniques. MATLAB/Simulink is used to simulate the outcomes for both the suggested control approach and the traditional Phase Disposition (PD) PWM control method whereas the leakage current component reduces to 25 % compared to the captured component with the PDPWM. The simulation and the practical results based on the dSPACE-1103 hardware are quite similar.

Solid fuels are widely used in China and increase the concentrations of indoor air pollutants. Nevertheless, there is limited longitudinal evidence linking solid fuel use and Gastrointestinal (GI) and liver diseases. This study aimed to prospectively investigate the association between household solid fuel use and the risk of GI and liver diseases in middle aged and elderly adults. This work was based on the China Health and Retirement Longitudinal Study (CHARLS). Longitudinal data incorporate with cross-sectional data were analyzed. Compared with individuals using clean fuel for cooking, solid fuel users were observed to have higher risk of GI diseases (OR in 2011, 2013, 2015, 2018 wave separately: 1.37, 95 % CI: 1.24–1.50, P

The real-time transmission of online monitoring data for high-voltage transmission equipment in remote areas is a difficult problem in practical applications due to the lack of network. For this purpose, the article designs an online monitoring system for high-voltage transmission equipment based on ubiquitous IoT and LoRa technology. It constructs a low-power, long-distance LoRa wireless communication self-organizing network, transmits the transmission equipment status information and other data collected by front-end sensors to the LoRaWAN gateway, and then uploads the data to the back-end server through a 5G wireless network to achieve the overall communication link of the online monitoring system. The simulation experiment results show that compared with the existing technical solutions ZigBee, LoRa, and NB-IoT, using the scheme designed in the article, the system transmission speed (20-100 kbit/s) is the fastest, and the packet loss rate, transmission delay, and average time consumption (1.6%, 0.27s, and 60s, respectively) are the lowest. This indicates that the system not only has a fast transmission speed but also takes into account the characteristics of low power consumption and long distance, achieving stable data transmission, and is suitable for online monitoring of high-voltage transmission equipment in remote areas.