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Abstract Background Radiation-induced myelopathy (RM) is a significant complication of radiotherapy with its mechanisms still not fully understood and lacking effective treatments. Compound 7 (C7) is a newly identified, potent, and selective inhibitor of the Keap1-Nrf2 interaction. This study aimed to explore the protective effects and mechanisms of C7 on RM in vitro and in vivo. Methods Western blotting, quantitative real‐time polymerase chain reaction (qRT‐PCR), reactive oxygen species (ROS) and mitochondrial polarization, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, genetic editing techniques, locomotor functions, and tissue staining were employed to explore the protective effects and underlying mechanisms of C7 in radiation-induced primary rat microglia and BV2 cells, as well as RM rat models. Results In this study, we found that C7 inhibited the production of pro-inflammation cytokines and oxidative stress induced by irradiation in vitro. Further, the data revealed that radiation worsened the locomotor functions in rats, and C7 significantly improved histological and functional recovery in RM rats. Mechanically, C7 activated Nrf2 signaling and promoted the microglia transformation from M1 to M2 phenotype. Conclusion C7 could ameliorate RM by boosting Nrf2 signaling and promoting M2 phenotype microglia polarization in vitro and in vivo.

Abstract Most vertebrates, including humans, are highly adept at detecting and encoding biological motion, even when it is portrayed by just a few point lights attached to the head and major joints. However, the function of subcortical regions in biological motion perception has been scarcely explored. Here, we investigate the role of the superior colliculus in local biological motion processing. Using high-field (3 T) and ultra-high-field (7 T) functional magnetic resonance imaging, we record the neural responses of the superior colliculus to scrambled point-light walkers (with local kinematics retained) in both humans and male macaque monkeys. Results show that the superior colliculus, especially the superficial layers, selectively responds to local biological motion. Furthermore, dynamic causal modeling analysis reveals a subcortical-cortical functional pathway that transmits local biological motion signals from the superior colliculus via the middle temporal visual complex to the posterior superior temporal sulcus in the human brain. These findings suggest the existence of a cross-species mechanism in the superior colliculus that facilitates the detection of local biological motion at the early stage of the visual processing stream.

Abstract Background New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. Specific abnormalities in gray matter and white matter structure are associated with pain, but have not been well studied in NDPH. The objective of this work is to explore the fiber tracts and structural connectivity, which can help reveal unique gray and white matter structural abnormalities in NDPH. Methods The regional radiomics similarity networks were calculated from T1 weighted (T1w) MRI to depict the gray matter structure. The fiber connectivity matrices weighted by diffusion metrics like fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) were built, meanwhile the fiber tracts were segmented by anatomically-guided superficial fiber segmentation (Anat-SFSeg) method to explore the white matter structure from diffusion MRI. The considerable different neuroimaging features between NDPH and healthy controls (HC) were extracted from the connectivity and tract-based analyses. Finally, decision tree regression was used to predict the clinical scores (i.e. pain intensity) from the above neuroimaging features. Results T1w and diffusion MRI data were available in 51 participants after quality control: 22 patients with NDPH and 29 HCs. Significantly decreased morphological similarity was found between the right superior frontal gyrus and right hippocampus. The superficial white matter (SWM) showed significantly decreased FA in fiber tracts including the right superficial-frontal, left superficial-occipital, bilateral superficial-occipital-temporal (Sup-OT) and right superficial-temporal, meanwhile significant increased RD was found in the left Sup-OT. For the fiber connectivity, NDPH showed significantly decreased FA in the bilateral basal ganglion and temporal lobe, increased MD in the right frontal lobe, and increased RD in the right frontal lobe and left temporal-occipital lobe. Clinical scores could be predicted dominantly by the above significantly different neuroimaging features through decision tree regression. Conclusions Our research indicates the structural abnormalities of SWM and the neural pathways projected between regions like right hippocampus and left caudate nucleus, along with morphological similarity changes between the right superior frontal gyrus and right hippocampus, constitute the pathological features of NDPH. The decision tree regression demonstrates correlations between these structural changes and clinical scores.

Abstract Changes in diet causing ecological stress pose a significant challenge to animal survival. In response, the gut microbiota, a crucial part of the host’s digestive system, exhibits patterns of change reflective of alterations in the host’s food component. The impact of temporal dietary shifts on gut microbiota has been elucidated through multidimensional modeling of both food component and macronutrient intake. However, the broad distribution of wild generalist and the intricate complexity of their food component hinder our capacity to ascertain the degree to which their gut microbiota assist in adapting to spatial dietary variations. We examined variation in patterns of the gut microbial community according to changes in diet and in a colobine monkey with a regional variable diet, the golden snub-nosed monkey (Rhinopithecus roxellana). Specifically, we analyse the interactions between variation in food component, macronutrient intake and the gut microbial community. We compared monkeys from four populations by quantifying food component and macronutrient intake, and by sequencing 16S rRNA and the microbial macro-genomes from the faecal samples of 44 individuals. We found significant differences in the diets and gut microbial compositions, in nutrient space and macronutrient intake among some populations. Variations in gut microbiota composition across distinct populations mirror the disparities in macronutrient intake, with a notable emphasis on carbohydrate. Geographical differences in the diet among of golden snub-nosed monkey populations will result in macronutrient intake variation, with corresponding differences in macronutrient intake driving regional differences in the compositions and abundances of gut microbiota. Importantly, the gut microbiota associated with core digestive functions does not vary, with the non-core gut microbiota fluctuating in response to variation in macronutrient intake. This characteristic may enable species heavily reliant on gut microbiota for digestion to adapt to diet changes. Our results further the understanding of the roles gut microbiota play in the formation of host dietary niches.

The flow behavior and deformation mechanisms of the [001]-oriented single-crystal nickel-based superalloy PWA1483 are investigated under quasi-static compressive and tensile loading conditions at 750°C. We found that the tensile yield strength is larger as compared to the compressive strength, and the serrated flow only appears on the compressive stress–strain curves. Microstructural observations uncover that stacking fault shearing and microtwinning are prone to initiate in PWA1483 during tensile deformation, and the appearance of the Protevin–Le Châtelier effect in compression derives from the abrupt frequent bursts of the two mechanisms on a mesoscale, rather than the simple occurrence of these procedures.

Ultrasonic metal welding machines are suitable for various complex applications (e.g., battery tabs) through unique mechanical design, special pressure application methods and high-precision welding. This work reports the weldability, forming quality and fractographic analysis of copper multilayered welded joints which were studied by SEM-EDS characterization, micro-hardness testing and tensile testing based on ultrasonic double roller welding (UDRW). Three groups of process parameters (A, B and C) were established to investigate the performance, production quality and welded joint surface interconnections. The tensile testing results of sample under parameter 3 in group A [S-P3(A)] indicate the maximum tensile strength of 69.859 N in T-peel test while the average tensile strength has increased by 58.525 N due to rise in welding time from 2 sec to 5 sec. The results analysis indicates that welding quality features in S-P3(A) joints under 4 bar, 100 mm/s, 45 % have been exploited. The over-welded zone was transformed into good-welded zone. The micro-cracks, fatigue stations and peeling texture in multilayers were reduced. It was found that when the welding energy was 10000 J then the tearing edges and interlayers cracks were minimized while keeping the other parameters constant. Moreover, when the amplitude increased up to 50 %, then numerous micro-cracks and micro-fissure stations were created, which leads to the occurrence of fracture in multi-layer welded joint. The EDS study investigated that the complex features are formed at the interface junction of sample 3 S3(A) in multilayer welds. The complex multilayer microstructures can induce and produce unique hardness properties for battery manufacturing. It leads to high quality and durable welds. Eventually, it is experimentally demonstrated that robust 40 layer welded joints can be obtained by the UDRW process. Data availability: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abstract Grain hardness has important effects on grain quality and the end-use of wheat. In this study, a collection of 103 common wheat germplasms and a DH population of 194 lines were used to identify new quantitative trait loci (QTL) for grain hardness. Two stable genetic loci on chromosome 5D were detected under different locations and years with one of them being the Ha locus on 5DS where the major gene Puroindolines for wheat grain hardness is located. Another locus of qTaHa-5DL also showed a significant impact on grain hardness index (HI) with HI increasing from ~ 20 to ~ 45 and hardness type changing from soft to mixed when Puroindolines are wild type. A kompetitive allele-specific PCR (KASP) marker for qTaHa-5DL was developed and the effectiveness of the QTL was confirmed in 184 breeding lines with the marker K-Ha5DL dividing wheat into two distinct categories. This new QTL can be effectively used to select soft or medium hard wheat.

Abstract Variable thickness plates are relatively common structure in large-scale transportation equipment such as aerospace and ships. Due to their high running speed and large structural dimensions, such structures are usually induced high-frequency severe vibrations, which likely lead to structural damage. Therefore, it is crucial to accurately predict the high-frequency dynamic response characteristics during the structural design phase. The energy finite element method (EFEM) is a powerful tool for predicting high-frequency dynamic response. But, in recent EFEM for variable thickness plates, an approximate method (AEFEM) using a large number of constant thickness plate elements to approximate variable thickness plates is used. Due to that AEFEM is based on the constitutive equation for constant thickness plate, it will be imprecise and time-consuming. Aiming at power-law variable thickness plates, the constitutive equation based on energy density is derived and the finite element discrete scheme of the constitutive equation was studied. In this way, the precise new EFEM (NEFEM) for variable thickness plates was established. In addition, the dynamic response of a variable thickness plate was predicted by NEFEM presented and finite element method (FEM) respectively. The results are consistent. It is shown that the constitutive model presented is reliable and time-saving. Comparison of the results from AEFEM, the NEFEM can get more accurate results with fewer elements. The NEFEM based on the constitutive model presented can be used to predict precisely the high-frequency dynamic response for power-law variable thickness plates.

Abstract Background Accurate differentiation between malignant and benign pulmonary nodules, especially those measuring 5–10 mm in diameter, continues to pose a significant diagnostic challenge. This study introduces a novel, precise approach by integrating circulating cell-free DNA (cfDNA) methylation patterns, protein profiling, and computed tomography (CT) imaging features to enhance the classification of pulmonary nodules. Methods Blood samples were collected from 419 participants diagnosed with pulmonary nodules ranging from 5 to 30 mm in size, before any disease-altering procedures such as treatment or surgical intervention. High-throughput bisulfite sequencing was used to conduct DNA methylation profiling, while protein profiling was performed utilizing the Olink proximity extension assay. The dataset was divided into a training set and an independent test set. The training set included 162 matched cases of benign and malignant nodules, balanced for sex and age. In contrast, the test set consisted of 46 benign and 49 malignant nodules. By effectively integrating both molecular (DNA methylation and protein profiling) and CT imaging parameters, a sophisticated deep learning-based classifier was developed to accurately distinguish between benign and malignant pulmonary nodules. Results Our results demonstrate that the integrated model is both accurate and robust in distinguishing between benign and malignant pulmonary nodules. It achieved an AUC score 0.925 (sensitivity = 83.7%, specificity = 82.6%) in classifying test set. The performance of the integrated model was significantly higher than that of individual methylation (AUC = 0.799, P = 0.004), protein (AUC = 0.846, P = 0.009), and imaging models (AUC = 0.866, P = 0.01). Importantly, the integrated model achieved a higher AUC of 0.951 (sensitivity = 83.9%, specificity = 89.7%) in 5–10 mm small nodules. These results collectively confirm the accuracy and robustness of our model in detecting malignant nodules from benign ones. Conclusions Our study presents a promising noninvasive approach to distinguish the malignancy of pulmonary nodules using multiple molecular and imaging features, which has the potential to assist in clinical decision-making. Trial registration: This study was registered on ClinicalTrials.gov on 01/01/2020 (NCT05432128). https://classic.clinicaltrials.gov/ct2/show/NCT05432128 .

Abstract Objective The efficacy of lymph node ratio (LNR) as a prognostic indicator in locally advanced gastric cancer (LAGC) patients underwent radical resection after neoadjuvant immunochemotherapy (NICT) remains to be demonstrated. The objective of the current retrospective study is to investigate the relationship between LNR and survival in patients with LAGC who underwent radical resection after NICT. Methods A retrospective analysis was performed on 121 cases of LAGC in patients underwent radical resection after NICT between July 2020 and October 2023. The LNR values of the patients were divided into two groups using X-tile software. The first group, designated the low LNR group, comprised patients with LNR values of ≤ 33%. The second group, designated the high LNR group, comprised patients with LNR values of > 33%. The correlation between patient survival rates and a range of clinical and pathological variables was examined. Results Overall, 121 patients were enrolled: 108 with low-LNR (LNR ≤ 33%) and 13 with high-LNR (LNR > 33%). A better 2-year overall survival (OS) (88.5% vs. 32.6%; p

Abstract Background In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high‐level clinical evidence. This study aimed to compare the safety and long‐term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. Methods A prospective, single‐center, open‐label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event‐free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. Results Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1‐3M0 to T2‐3N0‐3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1‐year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1‐year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien‐Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment‐related AEs did not differ between the two groups (12.5% versus 12.4%). Conclusions The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

Understanding the thermal conductivity of granite is critical for many geological and deep engineering applications. The heated granite was subjected to air-, water-, and liquid nitrogen (LN2-) coolings in this context. The transient hot-wire technique was used to determine the equivalent thermal conductivity (ETC) of the granite before and after treatment. The deterioration mechanism of ETC is analyzed from the meso-perspective. Finally, the numerical model is used to quantitatively study the impact of cooling rate on the microcrack propagation and heat conduction characteristics of granite. The results show that the ETC of granite is not only related to the heating temperature, but also affected by the cooling rate. The ETC of granite decreases nonlinearly with increasing heating temperature. A faster cooling rate causes a greater decrease in ETC at the same heating temperature. The higher the heating temperature, the stronger the influence of cooling rate on ETC. The main explanation for the decrease in ETC of granite is the increase in porosity and microcrack density produced by the formation and propagation of pore structure and microcracks during heating and cooling. Further analysis displays that the damage of granite at the heating stage is induced by the difference in thermal expansion and elastic properties of mineral particles. At the cooling stage, the faster cooling rate causes a higher temperature gradient, which in turn produces greater thermal stress. As a result, it not only causes new cracks in the granite, but also aggravates the damage at the heating stage, which induces a further decrease in the heat conduction performance of granite, and this scenario is more obvious at higher temperatures.

Abstract Background With the ongoing prevalence of the emerging variant and global vaccination efforts, the optimal surgical timing for patients with resectable lung cancer in the Omicron-dominant period requires further investigation. Methods This prospective multicenter study involved patients who underwent radical surgery for lung cancer between January 29, 2023 and March 31, 2023. Patients were categorized into four groups based on the interval between SARS-CoV-2 infection and surgery. The main outcomes evaluated were 30-day mortality and 30-day morbidity. Results A total of 2081 patients were enrolled in the study, of which 1837 patients (88.3%) had a confirmed SARS-CoV-2 diagnosis before surgery. Notably, no instances of 30-day mortality were observed in any patient. Patients without prior infection had a 30-day morbidity rate of 15.2%, with postoperative pneumonia occurring in 7.0% of cases. In contrast, patients diagnosed with SARS-CoV-2 before surgery had significantly higher rates of 30-day morbidity and postoperative pneumonia when surgery was performed within 4–5 weeks (adjusted odds ratio (aOR) (95% CI):2.18 (1.29–3.71) and 2.39 (1.21–4.79), respectively) or within 6–7 weeks (aOR (95% CI):2.07 (1.36–3.20) and 2.10 (1.20–3.85), respectively). Conversely, surgeries performed ≥ 8 weeks after SARS-CoV-2 diagnosis exhibited similar risks of 30-day morbidity and pneumonia compared to those in the no prior infection group (aOR (95% CI):1.13 (0.77–1.70) and 1.12 (0.67–1.99), respectively). Conclusions Thoracic surgery for lung cancer conducted 4–7 weeks after SARS-CoV-2 infection is still associated with an increased risk of 30-day morbidity in the Omicron-dominant period. Therefore, surgeons should carefully assess the individual risks and benefits to formulate an optimal surgical strategy for patients with lung cancer with a history of SARS-CoV-2 infection.

Abstract Background During the development of disease-modifying intervertebral disc degeneration (IDD) drugs, the rat model of IDD is frequently used for disease progression assessment. The aim of this study was to describe a magnetic resonance (MRI) scoring system for the assessment of different disc conditions in puncture-induced IDD, allowing standardization and comparison of results obtained by different investigators. Methods A total of 36 Sprague-Dawley rats were utilized in the present study. The animals were divided into two groups: a sham group and an IDD group caused by puncture. The rats in the IDD group were subsequently divided into six categories based on time frames, with five rats in each category. The sham group was divided into two sub-groups (n = 3) for 28 and 56 days, respectively. T2-weighted images of rats consecutively studied with MRI of the coccygeal discs were classified according to the time course using the corresponding histological data. Additional scoring of the micro-CT was employed to identify the progression of bone destruction of the rat model of IDD. Results A comparison of the MRI results between the sham group and the IDD group revealed a significant reduction in NP height, area, T2WI value, and DHI in the latter group (P

Abstract Background Chronic kidney disease (CKD) patients face the risk of rapid kidney function decline leading to adverse outcomes like dialysis and mortality. Lipid metabolism might contribute to acute kidney function decline in CKD patients. Here, we utilized the Mendelian Randomization approach to investigate potential causal relationships between drug target-mediated lipid phenotypes and rapid renal function decline. Methods In this study, we utilized two methodologies: summarized data-based Mendelian randomization (SMR) and inverse variance-weighted Mendelian randomization (IVW-MR), to approximate exposure to lipid-lowering drugs. This entailed leveraging expression quantitative trait loci (eQTL) for drug target genes and genetic variants proximal to drug target gene regions, which encode proteins associated with low-density lipoprotein (LDL) cholesterol, as identified in genome-wide association studies. The objective was to investigate causal associations with the progression of rapid kidney function decline. Results The SMR analysis revealed a potential association between high expression of PCSK9 and rapid kidney function decline (OR = 1.11, 95% CI= [1.001–1.23]; p = 0.044). Similarly, IVW-MR analysis demonstrated a negative association between LDL cholesterol mediated by HMGCR and kidney function decline (OR = 0.74, 95% CI = 0.60–0.90; p = 0.003). Conclusion Genetically predicted inhibition of HMGCR is linked with the progression of kidney function decline, while genetically predicted PCSK9 inhibition is negatively associated with kidney function decline. Future research should incorporate clinical trials to validate the relevance of PCSK9 in preventing kidney function decline.

Abstract Background Aberrant activation of mesenchymal epithelial transition (MET) has been considered to mediate primary and acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). However, mechanisms underlying this process are not wholly clear and the effective therapeutic strategy remains to be determined. Methods The gefitinib-resistant NSCLC cell lines were induced by concentration increase method in vitro. Western blot and qPCR were used to investigate the relationship between MET and vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling pathway. Double luciferase reporter gene and co-immunoprecipitation were used to further reveal the regulation mechanism between MET and VEGF/VEGFR2. The effect of combined inhibition of MET and VEGF/VEGFR2 signaling pathway on the therapeutic sensitivity of EGFR-TKI in gefitinib resistant cell lines with MET aberration was verified ex vivo and in vivo. Results We successfully obtained two gefitinib-resistant NSCLC cell lines with EGFR mutation and abnormal activation of MET. We observed that MET formed a positive feedback loop with the VEGF/VEGFR2 signaling, leading to persistent downstream signaling activation. Specifically, MET up-regulated VEGFR2 expression in a MAPK/ERK/ETS1-dependent manner, while VEGF promoted physical interaction between VEGFR2 and MET, thereby facilitating MET phosphorylation. A MET inhibitor, crizotinib, combined with an anti-VEGF antibody, bevacizumab, enhanced the sensitivity of NSCLC cells to gefitinib and synergistically inhibited the activation of downstream signaling in vitro. Dual inhibition of MET and VEGF combined with EGFR TKIs markedly restrained tumor growth in both human NSCLC xenograft models and in an EGFR/MET co-altered case. Conclusions Our work reveals a positive feedback loop between MET and VEGF/VEGFR2, resulting in continuous downstream signal activation. Combined inhibition of MET and VEGF/VEGFR2 signaling pathway may be beneficial for reversing EGFR TKIs resistance.

Abstract Background S100β is a biomarker of astroglial damage, the level of which is significantly increased following brain injury. However, the characteristics of S100β and its association with prognosis in patients with acute ischemic stroke following intravenous thrombolysis (IVT) remain unclear. Methods Patients in this multicenter prospective cohort study were prospectively and consecutively recruited from 16 centers. Serum S100β levels were measured 24 h after IVT. National Institutes of Health Stroke Scale (NIHSS) and hemorrhagic transformation (HT) were measured simultaneously. NIHSS at 7 days after stroke, final infarct volume, and modified Rankin Scale (mRS) scores at 90 days were also collected. An mRS score ≥ 2 at 90 days was defined as an unfavorable outcome. Results A total of 1072 patients were included in the analysis. The highest S100β levels (> 0.20 ng/mL) correlated independently with HT and higher NIHSS at 24 h, higher NIHSS at 7 days, larger final infarct volume, and unfavorable outcome at 3 months. The patients were divided into two groups based on dominant and non-dominant stroke hemispheres. The highest S100β level was similarly associated with the infarct volume in patients with stroke in either hemisphere (dominant: β 36.853, 95% confidence interval (CI) 22.659–51.048, P

Abstract Chronic gastritis (CG) is a common inflammatory disease of chronic inflammatory lesion of gastric mucosa and in the diagnosis of gastritis in traditional Chinese medicine (TCM), CG can be classified into Cold ZHENG (syndrome in TCM) and Hot ZHENG. However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. In this study, we collected a transcriptomics data including 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples. And 25 formulae for CG and 89 herbs recorded in these formulae were also collected. We conduct a comprehensive analysis based on the combination of transcriptomics datasets and machine learning algorithms, to discover biomarkers for Cold/Hot ZHENG CG. Then the target profiles of the collected formulae and Cold/Hot herbs were predicted to uncover the features and biomarkers of them against Cold/Hot ZHENG CG. These biomarkers suggest that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. Biomarkers and specific pathways of Hot herbs tend to regulate immune responses and energy metabolism, while those of Cold herbs are more likely to participate in anti-inflammatory effects. Finally, the findings were verified based on public transcriptomics datasets, as well as transcriptomics and ELISA detection, taking Jin Hong tablets as a case study. Biomarkers like leptin and IL-6 together with proportions of immune cells showed significant changes after the intervention. These findings might reflect the mechanism and build a bridge between macro and micro views of Cold/Hot ZHENG as well as Cold/Hot herbs. Graphical abstract

Abstract The potential benefit of neoadjuvant toripalimab plus axitinib in cases with clear cell renal cell carcinoma (ccRCC) and inferior vena cava tumor thrombus (IVC-TT) remains unclear. NEOTAX was a phase 2 study to investigate the efficacy and safety of neoadjuvant toripalimab plus axitinib in patients with ccRCC and IVC-TT (ChiCTR2000030405). The primary endpoint was the down-staging rate of IVC-TT level. Secondary endpoints included change in TT length, response rate, percentage change in surgical approach, surgical morbidity, progression-free survival (PFS), safety, and biomarker analyses. In all, 25 patients received study treatment, 44.0% (11/25) patients had a reduction in thrombus level, and none experienced an increase in Mayo level. The median change in tumor thrombus length was −2.3 cm (range: −7.1 to 1.1 cm). Overall, 61.9% (13/21) patients experienced changes in surgical strategy compared with planned surgery, three patients experienced major complications. The median PFS was 25.3 months (95% CI: 17.0-NE). The 1-year PFS was 89.1% (95% CI: 62.7–97.2). No any of grade 4 or 5 treatment-related adverse event was identified. Biopsy samples of non-responders exhibited increased T cytotoxic cell infiltration, but these cells were predominantly PD-1 positive. Biopsy samples of responders exhibited lower T helper cells, however, their subtype, regulatory T cells remained unchanged. In surgical samples of the TT, non-responders exhibited increased CD8T_01_GZMK_CXCR4 subset T cells. NEOTAX met preset endpoints proving that toripalimab in combination with axitinib downstages IVC-TT in a significant proportion of patients leading to simplification in the procedure of surgery.

Background and objective: Few studies on endoscopic management of primary obstructive megaureter (POM) in adult patients have been reported. Our objective was to describe our technique and long-term outcomes for endoscopic management of adult POM. Methods: We included 76 adult POM patients undergoing endoscopic management between September 2015 and January 2024. Under endoscopic control, the stricture was dilated to 24–30 Fr while maintaining a balloon pressure of 25–35 atm for 3 min. An additional incision of the stenotic ring using either an electrode or holmium laser was performed in 39 patients. Data for patient characteristics, intraoperative variables, surgical complications, and follow-up results were analyzed. A descriptive statistical analysis was performed. Surgical success was defined as no tubes or stents in the body, stable or improved symptoms and renal function, and the absence of reflux or obstruction during the follow-up period. Key findings and limitations: All procedures were completed without conversion to open or laparoscopic surgery. The median operative time was 45 min (range 16–165) with median estimated blood loss of 2 ml (range 0–150). The median postoperative hospital stay was 3 d (range 1–15). No intraoperative complication occurred. At median postoperative follow-up of 42 mo (range 3–100) the overall success rate was 92.1%. Restenosis of the vesicoureteral junction (Clavien-Dindo grade III) occurred in five patients (6.6%), and high-grade vesicoureteral reflux occurred in one patient (1.3%), all of whom required secondary reconstruction surgery. Conclusions and clinical implications: The results indicate that our endoscopic management for adult POM is safe and effective, with favorable long-term outcomes. This approach could potentially serve as a first-line treatment option for adult POM. Patient summary: Primary obstructive megaureter (POM) occurs when the flow of urine is blocked because of a narrow segment in the tube between the kidney and bladder (ureter), which causes widening of the ureter further up. For our minimally invasive technique, a telescope is inserted through the urethra and bladder to reach the ureter for surgical treatment. Our results show that this is a safe procedure for POM in adults.

Quantum power system state estimation (QPSSE) offers an inspiring direction for tackling the challenge of state estimation through quantum computing. Nevertheless, the current bottlenecks originate from the scarcity of practical and scalable QPSSE methodologies in the noisy intermediate-scale quantum (NISQ) era. This paper devises a NISQ−QPSSE algorithm that facilitates state estimation on real NISQ devices. Our new contributions include: (1) A variational quantum circuit (VQC)-based QPSSE formulation that empowers QPSSE analysis utilizing shallow-depth quantum circuits; (2) A variational quantum linear solver (VQLS)-based QPSSE solver integrating QPSSE iterations with VQC optimization; (3) An advanced NISQ-compatible QPSSE methodology for tackling the measurement and coefficient matrix issues on real quantum computers; (4) A noise-resilient method to alleviate the detrimental effects of noise disturbances. The encouraging test results on the simulator and real-scale systems affirm the precision, universality, and scalability of our QPSSE algorithm and demonstrate the vast potential of QPSSE in the thriving NISQ era.

Abstract Clinical trials on innovative drugs in China have witnessed a stage of rapid development in recent years. The introduction of a number of government policies has stimulated enthusiasm for research and development in the pharmaceutical industry. We analyzed the data of the early-phase clinical trials registered in the Chinese Center for Drug Evaluation (CDE) from September 6, 2013, to December 31, 2022. All related registration information disclosed on the CDE website, including posted time, drug classification, dosing formula, indications, trial design, and trial status, were summarized and analyzed. A total of 5336 early-phase clinical trials were identified. The quantity and growth rate of early-phase clinical trials have increased substantially each year. Chemical drugs accounted for the largest proportion of early-phase clinical trials, although it dropped from 85.7% in 2013 to 59.5% in 2022. Moreover, the number of oncology drugs has increased yearly, accounting for 49.2% of all early-phase clinical trials in 2022. We can conclude that during 2013–2022, the development of early-phase clinical trials has progressed due to government support and advanced development techniques. To enhance the efficiency and success rate of early-phase clinical trials in the future, it is necessary to acquire advanced technical support and improve standardized supervision systems.

Abstract The partial exposure of submarine cable may cause damage to the metal sheath, which will affect its safe and stable operation. Existing detection methods for burial depth of submarine cables are difficult to implement and have a long detection period. In this contribution, a method is proposed to calculate the burial depth of alternating current (AC) submarine cable based on surface optical fiber monitoring temperature. According to the functional relationship between the transient temperature rise of submarine cable outer sheath above the ambient temperature and the burial depth (in the IEC‐60853 standard), the burial depth of submarine cables is calculated. The optical fiber temperature, electric load and meteorological temperature data are used for 30 consecutive days in September 2020 to calculate the change of burial depth of AC 500 kV oil‐filled submarine cable. The calculation results are basically consistent with the detection conclusion of side‐scan sonar, which shows that the method can accurately calculate the burial depth of submarine cables and locate the exposed position. This provides a theoretical basis for the intelligent operation and maintenance of AC submarine cables.

In our increasingly electrified society, electricity has become indispensable to both production and daily life. However, high-load electric energy transmission presents inherent safety risks. To ensure the secure transportation of electric energy, live work on distribution networks is essential. However, traditional live work techniques require a high level of dependence on worker experience, which frequently leads to inaccurate safety distances and degrades worker security. This study proposes the integration of Unmanned Aerial Vehicles (UAVs) with intelligent robot sensing technology to enhance safety and efficiency in live work. By accurately measuring safety distances, UAVs offer a promising solution to mitigate risks associated with high-voltage circuits. Comparative analysis between traditional and intelligent live work safety distance measurements reveals the two live works under the high voltage circuit were 92% and 96%, respectively, and the accuracy of the two live work safe distance measurements under the low voltage circuit was 84% and 99%, respectively. Results demonstrate that UAVs equipped with intelligent sensing technology achieve superior accuracy in safe ranging for live work, thereby ensuring stable energy transmission and safeguarding the lives of workers in distribution networks. Doi: 10.28991/HIJ-2024-05-03-04 Full Text: PDF

Intracranial dural arteriovenous fistula (DAVF) is a relatively complex intracranial condition, and its clinical presentation and treatment strategies often vary significantly due to various factors. Although the cure rate of intracranial DAVF is currently high, there is still a lack of understanding of its etiology and pathogenesis. There is ongoing controversy regarding the treatment strategies for DAVF associated with the pial arteries, and there is a lack of understanding of its pathogenesis. The author conducted a brief literature review on DAVF with pial arterial supply and presented some treatment experiences from their own medical center. Large-scale retrospective cohort studies and prospective research in future are expected to address these issues.

Abstract Glioblastoma is a Grade 4 primary brain tumor defined by therapy resistance, diffuse infiltration, and near-uniform lethality. The underlying mechanisms are unknown, and no treatment has been curative. Using a recently developed creatine kinase inhibitor (CKi), we explored the role of this inhibitor on GBM biology in vitro. While CKi minimally impacted GBM cell proliferation and viability, it significantly affected migration. In established GBM cell lines and patient-derived xenografts, CKi ablated both the migration and invasion of GBM cells. CKi also hindered radiation-induced migration. RNA-seq revealed a decrease in invasion-related genes, with an unexpected increase in glutathione metabolism and ferroptosis protection genes post-CKi treatment. The effects of CKi could be reversed by the addition of cell-permeable glutathione. Carbon-13 metabolite tracing indicated heightened glutathione biosynthesis post-CKi treatment. Combinatorial CKi blockade and glutathione inhibition or ferroptosis activation abrogated cell survival. Our data demonstrated that CKi perturbs promigratory and anti-ferroptotic roles in GBM, identifying the creatine kinase axis as a druggable target for GBM treatment.

Abstract Low-cost, efficient catalyst high-throughput screening is crucial for future renewable energy technology. Interpretable machine learning is a powerful method for accelerating catalyst design by extracting physical meaning but faces huge challenges. This paper describes an interpretable descriptor model to unify activity and selectivity prediction for multiple electrocatalytic reactions (i.e., O2/CO2/N2 reduction and O2 evolution reactions), utilizing only easily accessible intrinsic properties. This descriptor, named ARSC, successfully decouples the atomic property (A), reactant (R), synergistic (S), and coordination effects (C) on the d-band shape of dual-atom sites, which is built upon our developed physically meaningful feature engineering and feature selection/sparsification (PFESS) method. Driven by this descriptor, we can rapidly locate optimal catalysts for various products instead of over 50,000 density functional theory calculations. The model’s universality has been validated by abundant reported works and subsequent experiments, where Co-Co/Ir-Qv3 are identified as optimal bifunctional oxygen reduction and evolution electrocatalysts. This work opens the avenue for intelligent catalyst design in high-dimensional systems linked with physical insights.

This paper describes a three-dimensional and comprehensive method for completing the northern extension of the Maoshan fracture zone from deep to shallow. Gravity field data interpretation and geomagnetic survey were used to initially locate the rupture, followed by shallow seismic survey for precise positioning, and finally the upper rupture point was captured and its Quaternary activities were investigated according to the method of joint geologic profile exploration with small spaced drill holes across the rupture point. Research has found: ① The Maoshan fracture zone continues to extend northward into the urban area of Zhenjiang, and the northern extension of the Maoshan fracture zone cuts at least to the mid-crustal region. ② The shallow part of the northern extension of the Maoshan fracture zone shows normal faulting characteristics, with an inclination to the east and a strike to the north-east, an apparent dip of about 60°, and an apparent break distance of about 3～5 m. ③ The results of the joint geologic profile of the boreholes show that the bedrock surface on both sides of the fracture point has a small difference, and the overlying Quaternary strata do not have any large undulation and do not have any obvious signs of Quaternary activity, so it is comprehensively judged that the northern extension of the Maoshan fracture zone is a pre-Quaternary fracture. This study preliminarily suggests that the Maoshan fault may be geospatially linked to two significant seismic events in the history of the Jiangsu landmass. This finding provides a new perspective for further research on the seismogenic tectonic features and seismic activity patterns in the region, and may inspire future related studies.

Abstract The Camellia oleifera meal (COM), a primary byproduct of oil-tea processing, often being discarded or used as a low-grade fertilizer due to its low value. The underutilization has become a significant bottleneck hindering the high-quality development of the oil-tea industry. In this study, the production of antibiotic-free feed additives through the solid-state fermentation of COM by Acremonium terricola was investigated. Our findings revealed that a saponin concentration of 5 mg/mL significantly enhanced the production of cordycepic acid (70.4 mg/g), ergosterol (3.32 mg/g), and chitin (110 mg/g) by A. terricola. This concentration also promoted chitin production and the activities of peroxidase (POD) and Na+/K+-ATPase, thereby maintaining cellular homeostasis and energy balance in A. terricola. Solid-state fermented rice bran (RB), wheat bran (WB), and desaponificated COM (containing 2.6 mg/100 g of tea saponin) were all found to be beneficial for increasing the production of cordycepic acid and ergosterol. The blend of COM, RB, and WB in the ratio of 15:65:20 was particularly advantageous for the production and accumulation of cordycepic acid and ergosterol, yielding 1.54 and 1.43 times, 1.27 and 1.37 times, and 1.98 and 5.52 times more than those produced by WB, RB, and COM alone, respectively.Meantime, the difference in contents of sugar and protein in A. terricola cultures (ATCs) using combination were not significant compared to RB and WB. These results indicated that COM can partially replace foodstuffs or food by-products to prepare antibiotic-free feed additives by A. terricola. Graphical Abstract

Abstract Background Dysbiosis of the microbiome is a key hallmark of polycystic ovary syndrome (PCOS). However, the interaction between the host and microbiome and its relevance to the pathogenesis of PCOS remain unclear. Methods To evaluate the role of the commensal gut microbiome in PCOS, we gavaged germ-free mice with the fecal microbiota from patients with PCOS or healthy individuals and evaluated the reproductive endocrine features of the recipient mice. Results Mice transplanted with fecal microbiota from PCOS patients and those transplanted from healthy controls presented different bacterial profiles and reproductive endocrine features. The fecal microbiota of the mice in the PCOS group was enriched in Phocaeicola, Mediterraneibacter, Oscillospiraceae, Lawsonibacter and Rikenellaceae. Fecal microbiota transplantation (FMT) from PCOS patients induced increased disruption of ovarian functions, lipo-metabolic disturbance, insulin resistance and an obese-like phenotype in recipient mice. Conclusion Our findings suggest that the microbiome may govern the set point of PCOS-bearing individuals and that gut ecosystem manipulation may be a useful marker and target for the management of PCOS.

The effect of final rolling temperature ranging from 962 to 696 °C on as-rolled high-Mn austenitic low-temperature steel was investigated using scanning electron microscopy, electron backscatter diffraction, transmission electron microscopy, and X-ray diffraction. The microstructure of the experimental steel remained austenite without suffering ferrite phase transformation, even when produced with a final rolling temperature as low as 696 °C. A decrease in the final rolling temperature of the steel was accompanied by a decrease in grain size from 20.2 to 6.0 μm, accompanied by an increase in dislocation density from 3.01 × 1014 to 10.9 × 1014 m−2. In addition, M23C6 carbides precipitated at the grain boundaries when the final rolling temperature was below 782 °C. Grain refinement and increased dislocation density significantly enhanced the strength of the material. However, an increase in the intragranular dislocation density compromised grain deformation ability. Moreover, the precipitation of M23C6 reduced the plasticity and toughness of the material. Considering the balance between yield strength and low-temperature toughness, the optimal final rolling temperature was 898 °C; this produced a material with a yield strength of approximately 507 MPa and a low-temperature impact energy absorption of approximately 143 J.

The collapse of high-steep dangerous rock is a common geological disaster in the mountainous areas of China. However, due to the limitation of objective factors such as traffic difficulties, the efficiency of artificial geological exploration is low and the safety risk is high, and the investigation in some places is unreachable. Based on the Laoshucuo 3# high-steep dangerous rock mass in the Three Gorges Reservoir area, this study established an analysis method system of high-steep dangerous rock mass by integrating UAV nap-of-the-object photogrammetry and airborne LiDAR technology. The three-dimensional geological model of Laoshucuo 3# dangerous rock mass was constructed systematically, and the engineering geological characteristics of the dangerous rock mass were characterized. The results show that there are five structural planes in the dangerous rock mass of Laoshucuo 3#, with the widest weak layer of 27.30 m and the deepest cavity of 2.19 m. The collapse type is toppling collapse. The stability coefficient of the dangerous rock mass is 1.375 under the natural condition, which is in a stable state, and 1.01 under the rainstorm condition, which is in an unstable state and needs to be treated. The technical method in this study has good complementarity to the investigation of high-steep dangerous rock mass, providing a new investigation method for non-contact measurement, geological information acquisition, and stability analysis of high-steep dangerous rock mass, and technical support for disaster prevention and mitigation in the reservoir area.

Tiger puffer is a commercially important fish cultured in high-density environments, and its accurate detection is indispensable for determining growth conditions and realizing accurate feeding. However, the detection precision and recall of farmed tiger puffer are low due to target blurring and occlusion in real farming environments. The farmed tiger puffer detection model, called knowledge aggregation YOLO (KAYOLO), fuses prior knowledge with improved YOLOv5 and was proposed to solve this problem. To alleviate feature loss caused by target blurring, we drew on the human practice of using prior knowledge for reasoning when recognizing blurred targets and used prior knowledge to strengthen the tiger puffer's features and improve detection precision. To address missed detection caused by mutual occlusion in high-density farming environments, a prediction box aggregation method, aggregating prediction boxes of the same object, was proposed to reduce the influence among different objects to improve detection recall. To validate the effectiveness of the proposed methods, ablation experiments, model performance experiments, and model robustness experiments were designed. The experimental results showed that KAYOLO's detection precision and recall results reached 94.92% and 92.21%, respectively. The two indices were improved by 1.29% and 1.35%, respectively, compared to those of YOLOv5. Compared with the recent state-of-the-art underwater object detection models, such as SWIPENet, RoIMix, FERNet, and SK-YOLOv5, KAYOLO achieved 2.09%, 1.63%, 1.13% and 0.85% higher precision and 1.2%, 0.18%, 1.74% and 0.39% higher recall, respectively. Experiments were conducted on different datasets to verify the model's robustness, and the precision and recall of KAYOLO were improved by approximately 1.3% compared to those of YOLOv5. The study showed that KAYOLO effectively enhanced farmed tiger puffer detection by reducing blurring and occlusion effects. Additionally, the model had a strong generalization ability on different datasets, indicating that the model can be adapted to different environments, and it has strong robustness.

The morphology is the consequence of evolution and adaptation. Escherichia coli is rod-shaped bacillus with regular dimension of about 1.5 μm long and 0.5 μm wide. Many shape-related genes have been identified and used in morphology engineering of this bacteria. However, little is known about if specific metabolism and metal irons could modulate bacteria morphology. Here in this study, we discovered filamentous shape change of E. coli cells overexpressing pigeon MagR, a putative magnetoreceptor and extremely conserved iron-sulfur protein. Comparative transcriptomic analysis strongly suggested that the iron metabolism change and iron accumulation due to the overproduction of MagR was the key to the morphological change. This model was further validated, and filamentous morphological change was also achieved by supplement E. coli cells with iron in culture medium or by increase the iron uptake genes such as entB and fepA. Our study extended our understanding of morphology regulation of bacteria, and may also serves as a prototype of morphology engineering by modulating the iron metabolism.

Abstract Achelura yunnanensis is a destructive pest of forests, causing substantial damage on tree growth and severe economic losses. Additionally, as a daytime-active moth, this species also holds important scientific value for investigating the genetic mechanisms governing day-night activity patterns of Lepidoptera. To facilitate effective pest control and deepen our understanding of the diurnal behavior’s genetic basis of moths, genomic data for this species are crucial. In this study, we present a chromosome-level reference genome of A. yunnanensis (368.15 Mb in 32 chromosomes; scaffold N50 = 12.61 Mb; BUSCO completeness = 98.0%). Genome annotation shows that the new assembly comprises 37.10% (136.55 Mb) repetitive elements, 1,828 non-coding RNAs, and 15,523 protein-coding genes. Genes involved in lipid metabolism and xenobiotics biodegradation and metabolism, such as cytochrome P450 families, experienced significant expansion in the A. yunnanensis genome. The chromosome-level genome of A. yunnanensis provides a valuable genomic resource for devising novel pest control strategies, and will also help to study the genetic mechanism of the shift of diurnal behavior in Lepidoptera.

Abstract Background Migraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR). Methods We utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein–protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets. Results We identified 35 protein targets for migraine and its subtypes (p

Abstract Alzheimer’s disease (AD), characterized by cognitive decline, is increasingly recognized as a disorder marked by synaptic loss and dysfunction. Despite this understanding, the underlying pathophysiological mechanisms contributing to synaptic impairment remain largely unknown. In this study, we elucidate a previously undiscovered signaling pathway wherein the S-nitrosylation of the Cdk5 activator p39, a post-translational modification involving the addition of nitric oxide to protein cysteine residues, plays a crucial role in synaptic dysfunction associated with AD. Our investigation reveals heightened p39 S-nitrosylation in the brain of an amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mouse model of AD. Additionally, soluble amyloid-β oligomers (Aβ), implicated in synaptic loss in AD, induce p39 S-nitrosylation in cultured neurons. Notably, we uncover that p39 protein level is regulated by S-nitrosylation, with nitric oxide S-nitrosylating p39 at Cys265 and subsequently promoting its degradation. Furthermore, our study demonstrates that S-nitrosylation of p39 at Cys265 significantly contributes to amyloid-β (Aβ) peptide-induced dendrite retraction and spine loss. Collectively, our findings highlight S-nitrosylation of p39 as a novel aberrant redox protein modification involved in the pathogenesis of AD, suggesting its potential as a therapeutic target for the disease.

Objective: To investigate the substantial changes in cell types, pathways, and cell-cell interactions occurring in the irradiation-induced alopecia and dermatitis (IRIAD) mouse model and to identify potential targets for patients experiencing skin adverse reactions to radiotherapy. Methods: Mice were irradiated at 15 ​Gy, targeting the head and neck region. After a 14-day interval, living cells were extracted from both wild-type (WT) mice and irradiated mice for single-cell RNA sequencing (scRNA-seq). The scRNA-seq data, retrieved from the GEO database (GSE201447), underwent stringent quality control using the Seurat (v4.3.0) R package. Cell type annotation relied on previously reported typical markers and CellMarker 2.0. Differentially expressed genes were calculated to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Cell-cell interactions were evaluated using the Cellchat R package. Results: The application of single-cell RNA sequencing (scRNA-seq) enabled a comprehensive characterization of the intricate cellular composition of both wild-type (WT) and irradiated mice skin. Remarkably, cells within irradiated mice skin exhibited a significant alteration in the intensity of cell-cell interactions compared to their wild-type counterparts. This change in interaction intensity was observed across various cell types, including fibroblast cells, endothelial cells, and dendritic cells. Importantly, these ''interacting cells'' shared common signaling pathways, notably the upregulation of the IL-17 pathway following irradiation. Conclusions: The modification of intercellular communication induced by irradiation primarily involves fibroblast cells, endothelial cells, and various types of immune cells. This investigation provides a novel perspective on potential targets and holds promise for enhancing the clinical management of IRIAD.

Ultrafine grained (UFG) n-C/Al composite bulk was obtained by mechanical milling and hot extrusion with petroleum coke utilized as carbon source. After extrusion, n-C sheets got dispersed and distributed in grain interiors or at grain boundaries. The tensile strength and corresponding thermal conductivity reached 407 ± 3 MPa and 216 ± 1.6 W m−1 K−1.

Recently, in order to strengthen the exploration and development of oil and gas resources in the Ordos Basin, seismic exploration has changed from a two-dimensional to a three-dimensional (3D) scale. With the progress of 3D seismic processing and interpretation technology, the data quality has improved each year. The Upper Paleozoic faults in the eastern Longdong region are of hidden low sequences with small fault spacings (

Developing new high-entropy rare-earth zirconate (HE-RE2Zr2O7) ceramics with low thermal conductivity is essential for thermal barrier coating materials. In this work, the average atomic spacings, interatomic forces, and average atomic masses of 16 rare-earth elements occupying the A site of the cubic A2B2O7 crystal structure were calculated by density functional theory. These three physical qualities, as vectors, characterize the corresponding rare-earth elements. The distance between two vectors quantitatively describes the difference between two rare-earth elements. For greater differences between two rare-earth elements, the disorder degree of HE-RE2Zr2O7 is greater, and therefore, the thermal conductivity is lower. According to the theoretical calculations, the thermal conductivity of the ceramics gradually increases in the order of (Sc0.2Y0.2La0.2Ho0.2Yb0.2)2Zr2O7, (Sc0.2Ce0.2Nd0.2Eu0.2Gd0.2)2Zr2O7, (Sc0.2Y0.2Tm0.2Yb0.2Lu0.2)2Zr2O7, and (Sc0.2Er0.2Tm0.2Yb0.2Lu0.2)2Zr2O7. Using the solution precursor plasma spray method and pressureless sintering method, four types of HE-RE2Zr2O7 powder and bulk samples were prepared. The samples all showed a single defective fluorite structure with a uniform distribution of the elements and a stable phase structure. The thermal conductivities of the sintered HE-RE2Zr2O7 bulk samples ranged from 1.30 to 1.45 W·m−1·K−1 at 1400 °C, and their differences were consistent with the theoretical calculation results. Among the ceramics, (Sc0.2Y0.2La0.2Ho0.2Yb0.2)2Zr2O7 had the lowest thermal conductivity (1.30 W∙m−1∙K−1, 1400 °C), highest thermal expansion coefficient (10.19×10−6 K−1, 200–1400 °C), highest fracture toughness (1.69±0.28 MPa∙m1/2), and smallest brittleness index (3.03 μm−1/2). Therefore, (Sc0.2Y0.2La0.2Ho0.2Yb0.2)2Zr2O7 is considered to be an ideal candidate material for next-generation thermal barrier coating applications.

Cold and Hot syndrome, also known as “ZHENG” in Mandarin, is a fundamental theory in traditional Chinese medicine (TCM) and plays a pivotal role in the differentiation of diseases in TCM. Diseases are treated with varying formulas according to the specific syndrome differentiations in TCM. A way of the principles followed in TCM medical strategy is “cold herbs for hot syndrome, and hot herbs for cold syndrome.” Therefore, from the perspective of cold/hot syndrome, we summarizes the present research regarding the characteristics and mechanisms of cold/hot herbs (including herbs with cool and warm properties) in digestive system diseases, respiratory diseases, and autoimmune diseases, among others. As novel technologies have advanced, various methods, such as those based on network target, machine learning, and deep learning, have emerged to reveal the mechanisms underlying cold/hot syndrome and cold/hot herbs. With the help of these technologies, it has been found that cold and hot herbs, as well as formulae with cold or hot intentions, have similarities and differences in the treatment of these diseases. In conclusion, cold and cool may have stronger antibacterial, antiviral, and anti-inflammatory effects, whereas hot and warm herbs may specifically enhance immune regulation. With the assistance of advancing data algorithms, uncovering the mechanisms of cold/hot herbs may accelerate and provide a new research paradigm for further achieving precision in TCM.

Abstract Background The aim of this study was to investigate the influence of marking methods on the outcomes of body composition analysis and provide guidance for the selection of marking methods in mouse body composition analysis. Methods Male C57BL/6J mice aged 6 weeks were randomly assigned for pre‐ and post‐ ear tagging measurements. The body composition of the mice was measured using a small animal body composition analyzer, which provided measurements of the mass of fat, lean, and free fluid. Then, the mass of fat, lean and free fluid to body weight ratio was gained. Further data analysis was conducted to obtain the range and coefficient of variation in body composition measurements for each mouse. The distribution of fat and lean tissue in the mice was also analyzed by comparing the fat‐to‐lean ratio. Results (1) The mass of all body composition components in the ear tagging group was significantly lower than that in the control group. (2) There was a significant increase in the range and coefficient of variation of body composition measurements between the ear tagging group and the control group. (3) The fat‐to‐lean ratio in the ear tagging group was significantly lower than that in the control group. Conclusions Ear tagging significantly lowered the results of body composition analysis in mice and higher the results of measurement error. Therefore, ear tagging should be avoided as much as possible when conducting body composition analysis experiments in mice.

Abstract Fiber optic sensors have been gradually used in aerospace, petrochemical, electronic power, civil engineering, and biomedical fields because of their many advantages such as the anti-electromagnetic interference, corrosion resistance, light weight, small size, high accuracy, and easy reuse. In recent years, sensing and demodulation technologies based on microwave photonics have attracted widespread attention. Optical fiber sensing combined with microwave photonics has higher sensitivity and flexibility, which is important for the demodulation of interferometric signals. This article introduces and analyzes the principle, structure, and performance of the demodulation technology of fiber optic interferometric signals based on microwave photonics from the perspective of system structures, such as filters, oscillators, and interferometers, and discusses the future research and development directions.

Abstract Polymeric elastomers are extensively employed to fabricate implantable medical devices. However, implantation of the elastomers can induce a strong immune rejection known as the foreign body response (FBR), diminishing their efficacy. Herein, we present a group of immunocompatible elastomers, termed easy-to-synthesize vinyl-based anti-FBR dense elastomers (EVADE). EVADE materials effectively suppress the inflammation and capsule formation in subcutaneous models of rodents and non-human primates for at least one year and two months, respectively. Implantation of EVADE materials significantly reduces the expression of inflammation-related proteins S100A8/A9 in adjacent tissues compared to polydimethylsiloxane. We also show that inhibition or knockout of S100A8/A9 leads to substantial attenuation of fibrosis in mice, suggesting a target for fibrosis inhibition. Continuous subcutaneous insulin infusion (CSII) catheters constructed from EVADE elastomers demonstrate significantly improved longevity and performance compared to commercial catheters. The EVADE materials reported here may enhance and extend function in various medical devices by resisting the local immune responses.

Abstract Epitaxial growth of two-dimensional (2D) materials with uniform orientation has been previously realized by introducing a small binding energy difference between the two locally most stable orientations. However, this small energy difference can be easily disturbed by uncontrollable dynamics during the growth process, limiting its practical applications. Herein, we propose a quasi-equilibrium growth (QEG) strategy to synthesize inch-scale monolayer α-In2Se3 single crystals, a semiconductor with ferroelectric properties, on fluor-phlogopite substrates. The QEG facilitates the discrimination of small differences in binding energy between the two locally most stable orientations, realizing robust single-orientation epitaxy within a broad growth window. Thus, single-crystal α-In2Se3 film can be epitaxially grown on fluor-phlogopite, the cleavage surface atomic layer of which has the same 3-fold rotational symmetry with α-In2Se3. The resulting crystalline quality enables high electron mobility up to 117.2 cm2 V−1 s−1 in α-In2Se3 ferroelectric field-effect transistors, exhibiting reliable nonvolatile memory performance with long retention time and robust cycling endurance. In brief, the developed QEG method provides a route for preparing larger-area single-crystal 2D materials and a promising opportunity for applications of 2D ferroelectric devices and nanoelectronics.

This paper proposes a method for creating a three-dimensional (above-ground and underground) fracture network in deep coalbed methane (CBM) reservoirs, which is the directional fracturing by slotted hydraulic blasting in underground drilling. First, theoretical analysis was conducted to explain the mechanism by which the slotted borehole enables the separation and incidence of explosive shock wave at the slot tip, resulting in the superposition of two sub-stress waves to cause directional fracture and damage to the rock. Then, LS-DYNA was used to simulate the process of directional fracturing by slotted hydraulic blasting to verify the theoretical mechanism. Finally, similar simulation experiments were performed on traditional blasting and slotted hydraulic blasting to confirm the directional fracturing effect of the proposed method. The results indicate that the slotted hydraulic blasting method can predominate the fracture orientation under formation stress, creating extensive directional fractures in rocks in the slot direction. This study is supplemental to the efforts on directional fracturing of rocks and provides a new approach for efficient exploitation of CBM.

Abstract Packetized energy encapsulates energy into modulated, routable, and trackable energy packets, enhancing the flexibility of managing distributed energy resources and expediting prosumers’ participation in transactive energy markets. In the context of packetized energy trading (PET), energy prosumers are naturally deemed as self‐interested agents seeking to obtain their own benefits. To align with prosumers’ demand, supply, quality of service (QoS), and system‐level social welfare, it is necessary to explore the design of prosumers’ bidding strategies and the market clearing methods, considering prosumers’ utility and the best demand response to markets. This study addresses challenges arising from prosumers’ selfishness and asymmetric preferences by proposing a PET‐oriented iterative double auction (IDA‐PET) design, where prosumers are allowed to iteratively change the bids before the auctioneer clears the market. Moreover, IDA‐PET accommodates system capacity constraints, energy balance, and economic constraints, providing cooperative strategies for both prosumers and the auctioneer. To validate the effectiveness of IDA‐PET, a novel and dedicated co‐simulation platform based on the hierarchical engine for large‐scale infrastructure co‐simulation platform is developed and case studies are conducted within a residential microgrid. The simulation results demonstrate that IDA‐PET can efficiently enhance the revenue of the auction market while meeting prosumers’ QoS requirements.