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Coal seam water injection can effectively inhibit gas gushing in the process of coal mining, and its inhibition effect mainly depends on the wetting characteristics of coal seam. The chemical structure of coal is one of the important factors affecting the wettability of coal. In order to study the relationship between the functional groups of medium and low rank coal and its wettability, the coal quality characteristics of typical medium and low rank coal samples were analyzed, and the parameters of different coal samples were obtained by Nicolet iN10 Fourier Transform microscopic infrared spectrometer. In this paper, the size of the contact Angle of deionized water at the solid-liquid-gas junction on the coal surface is used to characterize the wettability of coal. JC2000D contact Angle measuring instrument is used to obtain the contact Angle of different coal samples. Zeta potential can reflect wettability and ionization degree of coal surface functional groups, so as to establish the relationship between hydrophilic functional groups (hydroxyl functional groups, other oxygen-containing functional groups), contact Angle and Zeta potential of coal samples. The experimental results show that with the deepening of coal metamorphism, the strength of hydrophilic functional groups of coal samples decreases gradually, the peak height of hydrophilic functional groups of middle rank coal decreases by 0.13 compared with that of low rank coal, and the absorption peak area decreases by 58.91. The hydrophilic functional groups are negatively correlated with the contact Angle of coal samples, that is, the contact Angle decreases gradually with the increase of absorption peak intensity of hydrophilic functional groups, and the contact Angle decreases by 8.27 ° from middle rank coal samples to low rank coal samples. The relationship between hydrophilic functional groups and Zeta potential of coal samples shows a first-order exponential decay function, and the correlation coefficient is as high as 0.95. That is to say, the absolute value of Zeta potential increases gradually with the increase of absorption peak area of hydrophilic functional groups. The surface electronicity of coal samples is strong, and the hydrophilicity of coal is good. Among them, the hydroxyl functional group has a great influence on the wettability of coal, and the hydrogen bond formed by self-associating hydroxyl group is the main factor affecting the wettability of coal. Other oxygen-containing functional groups, such as carboxyl and ether bond hydrophilic functional groups, combine with water molecules under intermolecular force, showing strong vitality and improving the hydrophilicity of coal.

Abstract Synthetic high-performance fibers present excellent mechanical properties and promising applications in the impact protection field. However, fabricating fibers with high strength and high toughness is challenging due to their intrinsic conflicts. Herein, we report a simultaneous improvement in strength, toughness, and modulus of heterocyclic aramid fibers by 26%, 66%, and 13%, respectively, via polymerizing a small amount (0.05 wt%) of short aminated single-walled carbon nanotubes (SWNTs), achieving a tensile strength of 6.44 ± 0.11 GPa, a toughness of 184.0 ± 11.4 MJ m−3, and a Young’s modulus of 141.7 ± 4.0 GPa. Mechanism analyses reveal that short aminated SWNTs improve the crystallinity and orientation degree by affecting the structures of heterocyclic aramid chains around SWNTs, and in situ polymerization increases the interfacial interaction therein to promote stress transfer and suppress strain localization. These two effects account for the simultaneous improvement in strength and toughness.

Abstract Background Preexisting impaired renal function (IRF) and contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) are important prognostic parameters, but it is unknown whether delayed PCI is still beneficial for STEMI patients with IRF. Methods A retrospective single-center cohort study was performed in 164 patients who presented at least 12 h after symptom onset, and were diagnosed with STEMI and IRF. They were assigned to two groups to receive PCI plus optimal medical therapy (OMT) and OMT alone respectively. Clinical outcomes at 30 days and 1 year were compared between two groups, and hazard ratio for survival was analyzed using Cox regression model. A power analysis demanded 34 patients in each group to produce a power of 90% and a P value of 0.05. Results The 30-day mortality was significantly lower in PCI group (n = 126) than in non-PCI group (n = 38) (11.1% versus 28.9%, P = 0.018), while there was no significant difference in the 1-year mortality and incidence of cardiovascular comorbidities between the two groups. Cox regression analysis showed that patients with IRF didn’t benefit from receiving PCI on survival rate (P = 0.267). Conclusions Delayed PCI is not beneficial on one-year clinical outcomes for STEMI patients with IRF.

Abstract Cystic renal cell carcinoma (cRCC) is uncommon and surgical indication remains controversial. We compared radical nephrectomy (RN) with partial nephrectomy (PN) in patients with cRCC using data from the Surveillance, Epidemiology and End Results (SEER) database and a retrospective cohort including 106 cRCC patients hospitalized in Ruijin and Renji Hospitals from 2013 to 2022. The baseline characteristics between RN and PN groups in both cohorts were adjusted by propensity score-matching (PSM). A total of 640 patients were included in the SEER cohort. Before PSM, PN group in the SEER cohort had a lower level of T stage (p

Abstract Background Regulatory T cells (Tregs) play an important role in regulation of immune response and immunologic tolerance in cancer. Gastrointestinal cancer is still a leading cause of cancer-related death in the world. This study aimed to detect Tregs in patients with gastrointestinal cancer. Methods In this study, 45 gastric cancer patients, 50 colorectal cancer patients and 50 healthy controls were enrolled. Flow cytometry was used to detect CD4+CD25hiCD127low Tregs, CD4+CD25hi, and CD4+ cells in peripheral blood. Cytokine interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) in peripheral blood and in the supernatant of Tregs cultures were measured by enzyme linked immunosorbent assay. Results Compared with healthy controls, the levels of CD4+CD25hiCD127low Tregs and CD4+CD25hi cells increased significantly in patients with gastrointestinal cancer. Patients with gastrointestinal cancer also showed a significantly increased levels of IL-10 and TGF-β1 in both peripheral blood and CD4+CD25hiCD127low Tregs culture medium. Conclusion The present study firstly demonstrated that gastrointestinal patients have a compromised immune status where the CD4+CD25hiCD127low Tregs, as well as levels of IL-10 and TGF-β1 are elevated. The data offered new information for understanding the immunological features of gastrointestinal patients, as well as provided new insights into approaches to develop new immunotherapies for patients with gastrointestinal cancer.

Abstract Background IgA nephropathy (IgAN) is a common primary renal disease in childhood. Methods Twenty blood samples and renal tissue from patients with IgAN, 20 blood samples from healthy children and 10 normal renal tissue were collected. Serum Gd-IgA1 and renal Gd-IgA1, CD31, α-SMA and vimentin were measured. Results The serum Gd-IgA1 concentration in the IgAN group was significantly higher. Gd-IgA1 was not expressed in normal kidneys, which was positive in the IgAN group. Gd-IgA1 levels in serum and renal tissue were not related. The expression of CD31 decreased significantly in IgAN group, while the expression of α-SMA and vimentin increased significantly. There was no significant correlation between the renal concentration of Gd-IgA1 and CD31, α-SMA and vimentin. Conclusion The increased Gd-IgA1 in the serum and kidney may promote the pathogenesis of IgAN. The serum Gd-IgA1 cannot predict the extent of its deposition in the kidney. Endothelial mesenchymal transition (EndMT) may be involved in the pathogenesis of renal fibrosis in IgAN.

X-ray tomography has been widely used in various research fields thanks to its capability of observing 3D structures with high resolution non-destructively. However, due to the nonlinearity and inconsistency of detector pixels, ring artifacts usually appear in tomographic reconstruction, which may compromise image quality and cause nonuniform bias. This study proposes a new ring artifact correction method based on the residual neural network (ResNet) for X-ray tomography. The artifact correction network uses complementary information of each wavelet coefficient and a residual mechanism of the residual block to obtain high-precision artifacts through low operation costs. In addition, a regularization term is used to accurately extract stripe artifacts in sinograms, so that the network can better preserve image details while accurately separating artifacts. When applied to simulation and experimental data, the proposed method shows a good suppression of ring artifacts. To solve the problem of insufficient training data, ResNet is trained through the transfer learning strategy, which brings advantages of robustness, versatility and low computing cost.

Abstract Background Neoadjuvant chemotherapy is the standard treatment for local advanced breast cancer administered to shrink tumors and destroy undetected metastatic cells, thereby facilitating subsequent surgery. Previous studies have shown that AR may be used as a prognostic predictor in breast cancers, but its role in neoadjuvant therapy and the relationship with prognosis of different molecular subtypes of breast cancer need to be further explored. Methods We retrospectively evaluated 1231 breast cancer patients with complete medical records at Tianjin Medical University Cancer Institute and Hospital who were treated with neoadjuvant chemotherapy between January 2018 to December 2021. All the patients were selected for prognostic analysis. The follow-up time ranged from 12 to 60 months. We first analyzed the AR expression in different subtypes of breast cancer and its correlation with clinicopathological features. Meanwhile, the association of AR expression and pCR of different breast cancer subtypes was investigated. Finally, the effect of AR status on the prognosis of different subtypes of breast cancer after neoadjuvant therapy was analyzed. Results The positive rates of AR expression in HR + /HER2-, HR + /HER2 +, HR-/HER2 + and TNBC subtypes were 82.5%, 86.9%, 72.2% and 34.6%, respectively. Histological grade III (P = 0.014, OR = 1.862, 95% CI 1.137 to 2.562), ER positive expression (P = 0.002, OR = 0.381, 95% CI 0.102 to 0.754) and HER2 positive expression (P = 0.006, OR = 0.542, 95% CI 0.227 to 0.836) were independent related factors for AR positive expression. AR expression status was associated with pCR rate after neoadjuvant therapy only in subtype of TNBC. AR positive expression was independent protective factor for recurrence and metastasis in HR + /HER2- (P = 0.033, HR = 0.653, 95% CI 0.237 to 0.986) and HR + /HER2 + breast cancer (P = 0.012, HR = 0.803, 95% CI 0.167 to 0.959), but was independent risk factors for recurrence and metastasis in TNBC (P = 0.015, HR = 4.551, 95% CI 2.668 to 8.063). AR positive expression is not an independent predictor of HR-/HER2 + breast cancer. Conclusions AR expressed the lowest in TNBC, but it could be a potential marker for the prediction of pCR in neoadjuvant therapy. AR negative patients had a higher pCR rate. AR positive expression was an independent risk factor for pCR in TNBC after neoadjuvant therapy (P = 0.017, OR = 2.758, 95% CI 1.564 to 4.013). In HR + /HER2- subtype and in HR + /HER2 + subtype, the DFS rate in AR positive patients and AR negative patients was 96.2% vs 89.0% (P = 0.001, HR = 0.330, 95% CI 0.106 to 1.034) and was 96.0% vs 85.7% (P = 0.002, HR = 0.278, 95% CI 0.082 to 0.940), respectively. However, in HR-/HER2 + and TNBC subtypes, the DFS rate in AR positive patients and AR negative patients was 89.0% vs 95.9% (P = 0.102, HR = 3.211, 95% CI 1.117 to 9.224) and 75.0% vs 93.4% (P

The nasal microenvironment plays a crucial role in the transmission, modulation, and clinical progression of COVID-19; however, the immune responses at the site of viral entry remain poorly understood. We deciphered the link between nasopharyngeal (NP) immune and inflammatory response that triggers cytokine/chemokine storms in the nasal route of COVID-19-positive patients. We used RT-PCR, multiplex ELISA, flow cytometry, and LC-MS/MS to decipher nasopharyngeal immune perturbations associated with severe COVID-19. In addition, we performed in vitro assays using cultured human monocytes-derived macrophages trained both in the presence and absence of SARS-CoV-2 trimeric spike protein(s) and co-cultured with and without autologous human peripheral blood mononuclear cells (hPBMCs)/total T-cells/CD8 T-cells. In vitro immune perturbations were examined by flow cytometry and LC-MS/MS assays. Our findings confirm that macrophages orchestrate NP immune inflammatory responses and highlight the cytokine/chemokine storms associated with the increased CD8+T-cells along with Tregs, Th1, and Th17.1 T-helper cells. We observed a correlation between in vitro and nasal findings that trained macrophages, profoundly M2c, differentially promote the inflammatory surfactome on CD8 T-cells, including ITGAM, LGALS3, CD38, TKT, LRPAP1, and SSBP1. The findings of this study conclude that inflammatory lymphocyte perturbations within the nasopharynx of COVID-19 patients may enforce immune homeostasis during SARS-CoV-2-infection and contribute to COVID-19 pathology. This study explored the therapeutic target proteins that could facilitate the development of new medications, which could allow for immediate treatment of possible emerging viral infections.

The continuous emergence of new variants of concern for SARS-CoV-2 has created a challenge for existing therapies. To address this, we developed a series of single-stranded DNA aptamers that not only bind specifically to the trimer S protein of SARS-CoV-2 but also block the interaction between the trimer S protein and ACE2 receptors. The systematic evolution of ligands by exponential enrichment (SELEX) was performed to select the aptamers for SARS-CoV-2 trimer S protein. ELISA-based assay and flow cytometry were performed to test the apatmers’ binding and inhibition of trimer S protein in vitro. Binding affinity was measured using surface plasmon resonance. Significance was determined in Prism 9.0 using the one-way ANOVA test (Dunnett’s multiple comparisons test) or two-way ANOVA test (Tukey’s multiple comparisons test) for comparisons. The p values < 0.05 were considered statistically significant. After 12 rounds of SELEX, eight highly enriched aptamers were able to bind to the trimer S protein of the SARS-CoV-2 Wuhan original strain as well as the trimer S proteins of the Delta, Delta plus, Alpha, Lambda, Mu, and Omicron variants, with affinities in the nM range, while also inhibiting their interaction with ACE2 receptors in Vero E6 cells. Modifications to our best aptamer were made by adding forward and reverse primer sequences and truncation. The modified aptamers AYA2012004_L and AYA2012004_L-M1 showed up to 70% inhibition of the binding of virus-like particles (VLPs) expressing S protein to the ACE2 receptor expressed in HEK293T cells. Our findings imply that the selected aptamers can prevent SARS-CoV-2 from entering host cells and hence suppress the viral infection. In addition, the findings suggest that the selected aptamers might be an innovative therapy for the treatment of COVID-19.

Abstract The chiral charge density wave is a many-body collective phenomenon in condensed matter that may play a role in unconventional superconductivity and topological physics. Two-dimensional chiral charge density waves provide the building blocks for the fabrication of various stacking structures and chiral homostructures, in which physical properties such as chiral currents and the anomalous Hall effect may emerge. Here, we demonstrate the phase manipulation of two-dimensional chiral charge density waves and the design of in-plane chiral homostructures in 1T-TaS2. We use chiral Raman spectroscopy to directly monitor the chirality switching of the charge density wave—revealing a temperature-mediated reversible chirality switching. We find that interlayer stacking favours homochirality configurations, which is confirmed by first-principles calculations. By exploiting the interlayer chirality-locking effect, we realise in-plane chiral homostructures in 1T-TaS2. Our results provide a versatile way to manipulate chiral collective phases by interlayer coupling in layered van der Waals semiconductors.

Abstract Background Bacillus cereus infections in immunocompetent patients are uncommon and mainly observed in fragile patients. It can cause lethal infections with multiple organ dysfunction syndrome (MODS). However, a patient presenting as venous sinus thrombosis and survival without sequela has not been reported. Case presentation A 20-year-old previously healthy male developed gastroenteritis after a meal, followed by fever, convulsions, and severe disturbance of consciousness. The patient had significant leukocytosis with a mildly elevated D-dimer, creatinine level, and respiratory failure. The CT(computed tomography) revealed fatal brain edema and subarachnoid hemorrhage. Previous blood culture in a local hospital revealed B. cereus, which was confirmed by mNGS(metagenomic next-generation sequencing) using blood and urine in our hospital. Accordingly, B. cereus sepsis with MODS were considered. Later, cerebral venous sinus thrombosis was proved. After anti-infection (linezolid 0.6 g, Q12h; and meropenem 1.0 g, Q8h), anti-coagulant (enoxaparin 6000U, Q12h), and other symptomatic treatments, the patient recovered completely without sequela at the 6-month follow-up. Conclusions This case suggests that in immunocompetent adults, there is still a risk of infection with B. cereus, causing severe MODS. Special attention should be paid to venous sinus thrombosis and subarachnoid hemorrhage in such cases, while, anti-coagulant is essential therapy.

The performance of predictive current control (PCC) of induction motor (IM) drives is sensitive to the accuracy of the rotor flux angle estimation. In addition, predictive torque control (PTC), prioritizes control objectives by weighting factor in the cost function. It is tedious work to find a suitable weighting factor. In order to overcome these issues, a predictive power control (PPC) of IM drives is proposed in this paper. It directly controls the instantaneous output power of IM and does not require weighting factor and rotor flux angle estimation. This is achieved by the use of instantaneous power theory. The decoupling control of torque and rotor flux can be realized by controlling the output active and reactive power. The proposed method is easier to implement than PCC and PTC. To improve output efficiency, an output efficiency optimization strategy is proposed based on PPC. This is realized by adding the weighted output efficiency term into the cost function directly. Moreover, in order to get a better steady-state performance, an optimization strategy is proposed according to extend the output voltage vectors. Finally, the experimental and real-time hardware-in-the-loop (HiL) results validate that the proposed strategy is easier to implement and could optimize the output efficiency of the motor.

Frozen mandarin fish (MF) is utilized for preparation fermented MF. However, how raw material (RM) affects the quality and flavor of fermented MF is unclear. This study investigated the impact and mechanism of RM frozen storage on the microstructure, texture, water distribution, and flavor of fermented MF by light microscopy, texture profile analysis, low-field nuclear magnetic resonance, gas chromatography-ion mobility spectrometry, and multivariate analysis. With increasing RM frozen storage time, both frozen MF and frozen-based fermented MF decreased in muscle fiber density while increased in muscle fiber diameter. Additionally, RM frozen storage exhibited a significant impact on the water distribution of frozen MF, while no obvious effect on that of frozen-based fermented MF. Seven odorant (2-methyl-1-propanol, 3-hydroxy-2-butanone, 2,3-butanedione, hexanal-D, ethyl acetate-D, 3-pentanone, and acetone) were shown as potential markers to distinguish fermented MF. This study could provide a theoretical basis for the production of high-quality frozen-based fermented MF.

The effects of freeze-thawed cycles (FTs) and a new antifreeze protein from Sabina chinensis (Linn.) Ant. cv. Kaizuca leaves (ScAFP) on the structure and physicochemical characteristics of wheat starch were studied. The mechanical breaking exerted by ice crystals on starch granules during FTs gradually deepened, sequentially squeezing the surface (2–6 FTs), amorphous region (8 FTs) and crystalline region (10 FTs) of starch granules. These changes led to reduced thermal stability, increased retrogradation tendency, and weakened gel network structure. The addition of ScAFP retarded the damage of ice crystals on starch granule structure and crystal structure during FTs, and significantly reduced the retrogradation tendency. Compared with native starch, the hardness of freeze-thawed starch without and with added ScAFP after 10 FTs decreased by 17.85% and 9.22%, respectively, indicating ScAFP improved the gel texture properties of freeze-thawed starch. This study provides new strategies for improving the quality of frozen starch-based foods.

ATPase family AAA domain-containing protein 2 (ATAD2) has been emerging as a hot anti-cancer drugable target due to its oncogenic epigenetic modification closely associated with cancer cells proliferation, apoptosis, migration and drug resistance. In this study, we design a series of theophylline derivatives as novel ATAD2 inhibitors through fragment-based screening and scaffold growth strategy. A novel potent ATAD2 inhibitor (compound 19f) is discovered with an IC50 value of 0.27 μM against ATAD2, which adopts a combination of classic and atypical binding mode. Additionally, compound 19f could impede ATAD2 activity and c-Myc activation, induced significant apoptosis, and illustrated an anti-migration effect in BT-549 cells. Collectively, these results provide new enlightenment for the development of novel potent ATAD2 inhibitors for triple-negative breast cancer (TNBC) treatment.

Introduction: Tocilizumab and baricitinib are recommended treatment options for COVID-19 patients with hyperinflammatory response; however, there is a lack of systematic review directly evaluating their efficacy and safety.Objective: This review was conducted to evaluate the efficacy and safety of tocilizumab and baricitinib in the treatment of hospitalized patients with COVID-19.Methods: Relevant databases were searched for studies that compared the effect or safety of baricitinib or tocilizumab in hospitalized patients with COVID-19. The mortality was the main outcome. The hospital length of stay or adverse drug reactions were taken into consideration as secondary endpoints. The analyses were performed in Revman 5.3 or Stata 16.0. The protocol and analysis plan were pre-registered in PROSPERO, with the registration number CRD42023408219.Results: In total, 10 studies with 2,517 patients were included. The overall pooled data demonstrated that, there was no statistically significant difference in the 28-day mortality rate and the hospital length of stay between the tocilizumab and baricitinib (OR = 1.10, 95% CI = 0.80–1.51, p = 0.57; OR = −0.68, 95% CI = −2.24–0.87, p = 0.39). The adverse reactions including secondary infection rate, thrombotic and bleeding events, and acute liver injury of tocilizumab were significantly higher than that of baricitinib. (OR = 1.49, 95% CI = 1.18–1.88, p < 0.001,OR = 1.52, 95% CI = 1.11–2.08, p = 0.009; OR = 1.52, 95% CI = 1.11–2.08, p = 0.009; OR = 2.24, 95% CI = 1.49–3.35, p < 0.001).Conclusion: In patients hospitalized with COVID-19, no discernible difference in therapeutic efficacy was observed between tocilizumab and baricitinib; however, the group treated with baricitinib demonstrated a significantly lower incidence of adverse effects.

The North Huicheng Basin strike-slip fault system is on the northeastern frontier of the Tibetan Plateau and separates the West and East Qinling differential orogeny. However, the deformation mechanism of this strike-slip fault system and its exact tectonic significance are unclear. Here, we carried out systematic field structural analysis, physical analog modeling, and multiproxy geochronological dating to address these issues. The field structural analysis indicates that the North Huicheng Basin strike-slip fault system was induced from the plate-like movement of the West and East Qinling Orogens, which underwent multiple left-lateral strike-slip faulting and controlled salient and recessed structures. The scaled physical analog experiment results confirm this hypothesis and reveal the primary spatial-temporal deformational kinematic process. Combined with published works, multiproxy geochronological dating (zircon U‒Pb age of 213 Ma, biotite 40Ar/39Ar age of 203 Ma, and apatite fission-track age of 56 Ma) outlines the main thermal history of the hanging wall. Based on the above facts, the integrated research suggests that multistage strike-slip faulting played a significant role in the main tectonic events, that is, late Triassic magmatic emplacement, Jurassic/Cretaceous local pull-apart, and Cenozoic rapid exhumation driven by Tibetan Plateau growth.

BackgroundAutophagy plays a critical role in the progression of osteoarthritis (OA), mainly by regulating inflammatory and immune responses. However, the underlying mechanisms remain unclear. This study aimed to investigate the potential relevance of autophagy-related genes (ARGs) associated with infiltrating immune cells in OA.MethodsGSE114007, GSE169077, and ARGs were obtained from the Gene Expression Omnibus (GEO) database and the Human Autophagy database. R software was used to identify the differentially expressed autophagy-related genes (DEARGs) in OA. Functional enrichment and protein–protein interaction (PPI) analyses were performed to explore the role of DEARGs in OA cartilage, and then Cytoscape was utilized to screen hub ARGs. Single-sample gene set enrichment analysis (ssGSEA) was used to conduct immune infiltration analysis and evaluate the potential correlation of key ARGs and immune cell infiltration. Then, the expression levels of hub ARGs in OA were further verified by the GSE169077 and qRT-PCR. Finally, Western blotting and immunohistochemistry were used to validate the final hub ARGs.ResultsA total of 24 downregulated genes and five upregulated genes were identified, and these genes were enriched in autophagy, mitophagy, and inflammation-related pathways. The intersection results identified nine hub genes, namely, CDKN1A, DDIT3, FOS, VEGFA, RELA, MAP1LC3B, MYC, HSPA5, and HSPA8. GSE169077 and qRT-PCR validation results showed that only four genes, CDKN1A, DDT3, MAP1LC3B, and MYC, were consistent with the bioinformatics analysis results. Western blotting and immunohistochemical (IHC) showed that the expression of these four genes was significantly downregulated in the OA group, which is consistent with the qPCR results. Immune infiltration correlation analysis indicated that DDIT3 was negatively correlated with immature dendritic cells in OA, and FOS was positively correlated with eosinophils.ConclusionCDKN1A, DDIT3, MAP1LC3B, and MYC were identified as ARGs that were closely associated with immune infiltration in OA cartilage. Among them, DDIT3 showed a strong negative correlation with immature dendritic cells. This study found that the interaction between ARGs and immune cell infiltration may play a crucial role in the pathogenesis of OA; however, the specific interaction mechanism needs further research to be clarified. This study provides new insights to further understand the molecular mechanisms of immunity involved in the process of OA by autophagy.

Interactions between the central nervous system (CNS) and autonomic nervous system (ANS) play a crucial role in modulating perception, cognition, and emotion production. Previous studies on CNS–ANS interactions, or heart–brain coupling, have often used heart rate variability (HRV) metrics derived from electrocardiography (ECG) recordings as empirical measurements of sympathetic and parasympathetic activities. Functional near-infrared spectroscopy (fNIRS) is a functional brain imaging modality that is increasingly used in brain and cognition studies. The fNIRS signals contain frequency bands representing both neural activity oscillations and heartbeat rhythms. Therefore, fNIRS data acquired in neuroimaging studies can potentially provide a single-modality approach to measure task-induced responses in the brain and ANS synchronously, allowing analysis of CNS–ANS interactions. In this proof-of-concept study, fNIRS was used to record hemodynamic changes from the foreheads of 20 university students as they each played a round of multiplayer online battle arena (MOBA) game. From the fNIRS recordings, neural and heartbeat frequency bands were extracted to assess prefrontal activities and short-term pulse rate variability (PRV), an approximation for short-term HRV, respectively. Under the experimental conditions used, fNIRS-derived PRV metrics showed good correlations with ECG-derived HRV golden standards, in terms of absolute measurements and video game playing (VGP)-related changes. It was also observed that, similar to previous studies on physical activity and exercise, the PRV metrics closely related to parasympathetic activities recovered slower than the PRV indicators of sympathetic activities after VGP. It is concluded that it is feasible to use fNIRS to monitor concurrent brain and ANS activations during online VGP, facilitating the understanding of VGP-related heart–brain coupling.

Abstract To date, the restricted capability to fabricate ceramics with independently tailored nano‐ and macroscopic features has hindered their implementation in a wide range of crucial technological areas, including aeronautics, defense, and microelectronics. In this study, a novel approach that combines self‐ and digital assembly to create polymer‐derived ceramics with highly controlled structures spanning from the nano‐ to macroscale is introduced. Polymerization‐induced microphase separation of a resin during digital light processing generates materials with nanoscale morphologies, with the distinct phases consisting of either a preceramic precursor or a sacrificial polymer. By precisely controlling the molecular weight of the sacrificial polymer, the domain size of the resulting material phases can be finely tuned. Pyrolysis of the printed objects yields ceramics with complex macroscale geometries and nanoscale porosity, which display excellent thermal and oxidation resistance, and morphology‐dependent thermal conduction properties. This method offers a valuable technological platform for the simplified fabrication of nanostructured ceramics with complex shapes.

IntroductionOrdinal traits are important complex traits in crops, while genome-wide association study (GWAS) is a widely-used method in their gene mining. Presently, GWAS of continuous quantitative traits (C-GWAS) and single-locus association analysis method of ordinal traits are the main methods used for ordinal traits. However, the detection power of these two methods is low.MethodsTo address this issue, we proposed a new method, named MTOTC, in which hierarchical data of ordinal traits are transformed into continuous phenotypic data (CPData).ResultsThen, FASTmrMLM, one C-GWAS method, was used to conduct GWAS for CPData. The results from the simulation studies showed that, MTOTC+FASTmrMLM for ordinal traits was better than the classical methods when there were four and fewer hierarchical levels. In addition, when MTOTC was combined with FASTmrEMMA, mrMLM, ISIS EM-BLASSO, pLARmEB, and pKWmEB, relatively high power and low false positive rate in QTN detection were observed as well. Subsequently, MTOTC was applied to analyze the hierarchical data of soybean salt-alkali tolerance. It was revealed that more significant QTNs were detected when MTOTC was combined with any of the above six C-GWAs.DiscussionAccordingly, the new method increases the choices of the GWAS methods for ordinal traits and helps to mine the genes for ordinal traits in resource populations.

Pedotransfer functions (PTFs) have been developed for many regions to estimate values missing from soil profile databases. However, globally there are many areas without existing PTFs, and it is not advisable to use PTFs outside their domain of development due to poor performance. Further, developed PTFs often lack accompanying uncertainty estimations. To address these issues, a framework is proposed where existing equation-based PTFs are recalibrated using a nonlinear least squares (NLS) approach and validated on two regions of Canada; this process is coupled with the use of quantile regression (QR) to generate uncertainty estimates. Many PTFs have been developed to predict soil bulk density, so this variable is used as a case study to evaluate the outcome of recalibration. New coefficients are generated for existing soil bulk density PTFs, and the performance of these PTFs is validated using three case study datasets, one from the Ottawa region of Ontario and two from the province of British Columbia, Canada. The improvement of the performance of the recalibrated PTFs is evaluated using root mean square error (RMSE) and the concordance correlation coefficient (CCC). Uncertainty estimates produced using QR are communicated through the mean prediction interval (MPI) and prediction interval coverage probability (PICP) graphs. This framework produces dataset-specific PTFs with improved accuracy and minimized uncertainty, and the method can be applied to other regional datasets to improve the estimations of existing PTF model forms. The methods are most successful with large datasets and PTFs with fewer variables and minimal transformations; further, PTFs with organic carbon (OC) as one of or the sole input variable resulted in the highest accuracy.

Magnetic soft robots featuring untethered actuation and high mechanical compliance have promising applications ranging from bionics to biomedicine. However, their fixed magnetization profiles pose a challenge for adaptive shape transformation in unpredictable environments and dynamic tasks. Herein, a reprogrammable magnetic soft composite is reported by encapsulating magnetic neodymium–iron–boron microparticles with low melting alloy (LMA) and embedding them into the elastomer. Utilizing the phase transition of the LMA, the magnetic microparticles can be reoriented under an external magnetic field and they can be immobilized through LMA solidification, allowing the robot to obtain a new magnetization profile corresponding to its temporary shape. By changing the LMA composition, the robot with multiple programming temperatures can be fabricated and its local magnetization profiles can be selectively programmed in different temperature ranges. A bioinspired crawler with multimode locomotion, a reconfigurable robotic gripper capable of adaptable grasping, and reconfigurable electronic circuits are also demonstrated. This work may pave the way for the next‐generation magnetic soft robots and reconfigurable devices.

Abstract In recent years, cannabidiol (CBD), a non‐psychotropic cannabinoid, has garnered substantial interest in drug development due to its broad pharmacological activity and multi‐target effects. Diabetes is a chronic metabolic disease that can damage multiple organs in the body, leading to the development of complications such as abnormal kidney function, vision loss, neuropathy, and cardiovascular disease. CBD has demonstrated significant therapeutic potential in treating diabetes mellitus and its complications owing to its various pharmacological effects. This work summarizes the role of CBD in diabetes and its impact on complications such as cardiovascular dysfunction, nephropathy, retinopathy, and neuropathy. Strategies for discovering molecular targets for CBD in the treatment of diabetes and its complications are also proposed. Moreover, ways to optimize the structure of CBD based on known targets to generate new CBD analogues are explored.

It has been documented that calycosin induces anticancer effects against a wide range of cancer cells, in vitro. However, pharmacokinetic characteristics of calycosin based on its interaction with albumin as a main carrier protein as well as corresponding anticancer mechanisms remain largely unknown. Herein, we inquired into the interaction of calycosin with human serum albumin (HSA) by a wide range collection of spectroscopic and theoretical data. Also, anticancer effects of calycosin on breast cancer cells, MDA-MB 231, were explored by cell viability, lactate dehydrogenase (LDH), caspase-3 activity, and real-time PCR assays. The findings demonstrated that the quenching process resulting from the interaction of calycosin and HSA was largely static in nature and that the calycosin-HSA system spontaneously forms. Cellular and molecular studies revealed that calycosin did not induce a significant cytotoxic effect on the viability of normal human breast epithelial cells, (MCF-10A), even at 200 μM concentration at which it was able to inhibit the proliferation of breast cancer MDA-MB 231 cells up to 50%. Then, it was disclosed that calycosin can disrupt the membrane integrity and induces apoptosis in MDA-MB 231 cells through overexpression of caspase-3 mRNA, down regulation of Bcl-2, and elevation of caspase-3 mRNA and activity mediated by downregulation of mTOR and Akt mRNA. Therefore, it was realized that in breast cancer MDA-MB 231 cells, calycosin is able to suppress cellular proliferation via apoptosis, which is controlled by the Akt/mTOR signaling cascade.

Abstract Rationale Polymyositis (PM), which usually occurs in young and middle-aged females, is an inflammatory myopathy characterized by symmetrical proximal limb weakness, neck muscular weakness, and muscle soreness. Severe kidney injury performance caused by the primary disease is uncommon among patients with PM. In this case report, we described the clinical features and pathological clues to help diagnose this disease, furthermore, a review of the literature is provided. Patient concerns A 26-year-old female suffered from persistent weakness and pain in the limb muscles for 1 month and anuria for 1 week before admission. Diagnosis and interventions Serum creatine kinase (CK) level elevated five times above the limit of normal levels and the myositis autoantibody test was positive. Typical clinical symptoms and signs, laboratory results, and significant therapeutic efficacy of hormone therapy and biological therapy all revealed PM complicated with rhabdomyolysis (RML) clinically. After admission, the patient underwent renal replacement therapy, glucocorticoid treatment and was infused with tocilizumab. And the patient recovered and was discharged 4 months later. Outcomes During the conventional treatment, the patient remained in an unstable state. After glucocorticoid pulse treatment and biotherapy, her muscle force enhanced significantly and her general condition improved gradually. Lessons PM combined with RML is rare in clinics and easily misdiagnosed as simple RML, which delays the timing of treatment. This study was to explore the disease by reviewing one case and literatures, which would help for early diagnosis of this disease and then give a reasonable basis for future treatment. Glucocorticoids are still the first-line treatment for the disease.

This paper investigates the effect of anisotropic resolution on the image textural features of pharmacokinetic (PK) parameters of a murine glioma model using dynamic contrast-enhanced (DCE) MR images acquired with an isotropic resolution at 7T with pre-contrast T1 mapping. The PK parameter maps of whole tumors at isotropic resolution were generated using the two-compartment exchange model combined with the three-site-two-exchange model. The textural features of these isotropic images were compared with those of simulated, thick-slice, anisotropic images to assess the influence of anisotropic voxel resolution on the textural features of tumors. The isotropic images and parameter maps captured distributions of high pixel intensity that were absent in the corresponding anisotropic images with thick slices. A significant difference was observed in 33% of the histogram and textural features extracted from anisotropic images and parameter maps, compared to those extracted from corresponding isotropic images. Anisotropic images in different orthogonal orientations demonstrated 42.1% of the histogram and textural features to be significantly different from those of isotropic images. This study demonstrates that the anisotropy of voxel resolution needs to be carefully considered when comparing the textual features of tumor PK parameters and contrast-enhanced images.

Abstract Objective Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity. Methods Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP. Results The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP. Conclusion The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.

CO2 electroreduction to multi-carbon products in acids remains challenging due to the low efficiency and poor stability of C–C coupling. Here, the authors show that asymmetric CO binding at confined nanointerfaces enhances multi-carbon production, improves CO2 utilization, and limits H2 evolution.

Abstract Remote sensing is an important technical tool for rapid detection of illegal mining behavior. Due to the complex features of open-pit coal mines, there are few studies about automatic extraction of open-pit coal mines. Based on Convolutional Neural Network and Dense Block, we propose a lightweight densely connected network-AD-Net for the extraction of open-pit coal mining areas from Sentinel-2 remote sensing images, and construct three sample libraries of open-pit coal mining areas in north-central Xinzhou City, Shanxi Province. The AD-Net model consists of two convolutional layers, two pooling layers, a channel attention module, and a Dense Block. The two convolutional layers greatly reduce the complexity of the model, and the Dense Block enhances the feature propagation while reducing the parameter computation. The application is designed in different modules that runs independently on different machines and communicate with each other. Furthermore, we create and build a unique remote sensing image service system that connects a remote datacentre and its associated edge networks, employing the edge-cloud architecture. While the datacentre acts as the cloud platform and is in charge of storing and processing the original remote sensing images, the edge network is largely utilised for caching, predicting, and disseminating the processed images. First, we find out the optimal optimizer and the optimal size of the input image by extensive experiments, and then we compare the extraction effect of AD-Net with AlexNet, VGG-16, GoogLeNet, Xception, ResNet50, and DenseNet121 models in the study area. The experimental results show that the combination of NIR, red, green, and blue band synthesis is more suitable for the extraction of the open-pit coal mine, and the OA and Kappa of AD-Net reach 0.959 and 0.918 respectively, which is better than other models and well balances the classification accuracy and running speed. With this design of edge-cloud, the proposed system not only evenly distributes the strain of processing activities across the edges but also achieves data efficiency among them, reducing the cost of data transmission and improving the latency.

Abstract Cancer immunotherapy, mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells, has revolutionized the oncology landscape as it utilizes patients’ own immune systems in combating the cancer cells. Cancer cells escape immune surveillance by hijacking the corresponding inhibitory pathways via overexpressing checkpoint genes. Phagocytosis checkpoints, such as CD47, CD24, MHC-I, PD-L1, STC-1 and GD2, have emerged as essential checkpoints for cancer immunotherapy by functioning as “don’t eat me” signals or interacting with “eat me” signals to suppress immune responses. Phagocytosis checkpoints link innate immunity and adaptive immunity in cancer immunotherapy. Genetic ablation of these phagocytosis checkpoints, as well as blockade of their signaling pathways, robustly augments phagocytosis and reduces tumor size. Among all phagocytosis checkpoints, CD47 is the most thoroughly studied and has emerged as a rising star among targets for cancer treatment. CD47-targeting antibodies and inhibitors have been investigated in various preclinical and clinical trials. However, anemia and thrombocytopenia appear to be formidable challenges since CD47 is ubiquitously expressed on erythrocytes. Here, we review the reported phagocytosis checkpoints by discussing their mechanisms and functions in cancer immunotherapy, highlight clinical progress in targeting these checkpoints and discuss challenges and potential solutions to smooth the way for combination immunotherapeutic strategies that involve both innate and adaptive immune responses.

To explore the effects of different drying methods on lipid oxidation and volatile flavor components of fishery products, the corresponding experimental groups were prepared by hot-air drying, cold-air drying and traditional natural drying using fresh Spanish mackerel (Scomberomorus niphonius) as raw material. The moisture content, pH value, lipid content, acid value (AV), peroxide value (POV), malondialdehyde (MDA), fatty acid composition and volatile flavor components of raw materials and different dried samples were measured. The results showed that the moisture content of dried samples prepared by three drying methods was about 30% with the pH value above 6. The AV, POV and the contents of MDA in the cold-air drying group were lower than the other groups (P

Al–Cu–Mg–Fe–Ni alloys are widely used in high temperature structural materials such as automobile engine cylinders and pistons, owning to their good high temperature mechanical properties. In this work, the effect of Fe and Ni content, solution treated, and aged process on the microstructure and mechanical properties of Al–Cu–Mg–Fe–Ni alloys were investigated by optical microscopy (OM), scanning electron microscopy (SEM), hardness and tensile tests. Transmission electron microscope (TEM) and high–resolution TEM were used to determine the existence of S phase and Al9FeNi precipitates. The solution treatment followed by aged process is found to be of significant benefit in improving the tensile properties both at room– and elevated temperature.

[Objective] The accurate and rapid landslide susceptibility zoning method were studied in order to provide a reference for regional safety monitoring, and provide a scientific basis for the government to control landslide disasters. [Methods] The study was conducted in the Guichi District of Chizhou City, Anhui Province. The coupled model of gradient boosting decision tree-logistic regression (GBDT-LR) and an information value (I) model was used to determine the evaluation of regional landslide susceptibility. The model learns from the original samples and combines them to generate new simulation samples in order to enhance the fitting ability of the model to evaluate landslide susceptibility. The Borderline-Smote algorithm was used to solve the problem of sample data asymmetry. The slope unit divided by r.slopeunits software was selected as the minimum evaluation unit, and a total of 10 evaluation factors were selected: slope gradient, slope aspect, terrain curvature, profile curvature, plane curvature, topographic wetness index (TWI), topographic relief, normalized difference vegetation index (NDVI), distance from fault, and distance from river. The landslide susceptibility model was evaluated from three aspects: frequency ratio, density of landslide disaster points and hidden danger points, and the receiver operating characteristic (ROC) curve. [Results] The experimental results showed that the frequency ratio of the coupled model I-GBDT-LR was 10%, 13%, and 7% greater than that of the I, LR, and I-LR models, respectively. The density of landslide disaster points and hidden danger points in the high risk area increased by about 9, 11, and 7, respectively, and the ROC accuracy increased by about 10%, 9%, and 5%, respectively. [Conclusion] The accuracy of the coupled model was higher than that of the single model, and the accuracy of the coupled model proposed was higher than that of the I-LR coupled model, which provides an effective and new evaluation method for landslide susceptibility evaluation.

Abstract This manuscript aims to evaluate the robustness and significance of the water efflux rate constant (k io ) parameter estimated using the two flip-angle Dynamic Contrast-Enhanced (DCE) MRI approach with a murine glioblastoma model at 7 T. The repeatability of contrast kinetic parameters and k io measurement was assessed by a test–retest experiment (n = 7). The association of k io with cellular metabolism was investigated through DCE-MRI and FDG-PET experiments (n = 7). Tumor response to a combination therapy of bevacizumab and fluorouracil (5FU) monitored by contrast kinetic parameters and k io (n = 10). Test–retest experiments demonstrated compartmental volume fractions (v e and v p ) remained consistent between scans while the vascular functional measures (F p and PS) and k io showed noticeable changes, most likely due to physiological changes of the tumor. The standardized uptake value (SUV) of tumors has a linear correlation with k io (R2 = 0.547), a positive correlation with F p (R2 = 0.504), and weak correlations with v e (R2 = 0.150), v p (R2 = 0.077), PS (R2 = 0.117), K trans (R2 = 0.088) and whole tumor volume (R2 = 0.174). In the treatment study, the k io of the treated group was significantly lower than the control group one day after bevacizumab treatment and decreased significantly after 5FU treatment compared to the baseline. This study results support the feasibility of measuring k io using the two flip-angle DCE-MRI approach in cancer imaging.

Abstract Long non-coding RNAs (LncRNAs) are implicated in malignant progression of human cancers. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-known lncRNA, has been reported to play crucial roles in multiple malignancies including head and neck squamous cell carcinoma (HNSCC). However, the underlying mechanisms of MALAT1 in HNSCC progression remain to be further investigated. Here, we elucidated that compared with normal squamous epithelium, MALAT1 was notably upregulated in HNSCC tissues, especially in which was poorly differentiated or with lymph nodes metastasis. Moreover, elevated MALAT1 predicted unfavorable prognosis of HNSCC patients. The results of in vitro and in vivo assays showed that targeting MALAT1 could significantly weaken the capacities of proliferation and metastasis in HNSCC. Mechanistically, MALAT1 inhibited von Hippel–Lindau tumor suppressor (VHL) by activating EZH2/STAT3/Akt axis, then promoted the stabilization and activation of β-catenin and NF-κB which could play crucial roles in HNSCC growth and metastasis. In conclusion, our findings reveal a novel mechanism for malignant progression of HNSCC and suggest that MALAT1 might be a promising therapeutic target for HNSCC treatment.

Genomic and transcriptomic profiling in Jingxing yellow chickens selected for a heterophil-lymphocyte ratio (H/L) provides further insight on the genetic basis of H/L and identifies PTPRJ as a relevant factor.

Objective: According to Traditional Chinese Medicine theory, spleen deficiency and phlegm-dampness syndrome (SDPDS) are caused by abnormal water metabolism in the body because of spleen dysfunction. The purpose of this article was to evaluate the efficacy of D-limonene (DL) in resolving phlegm in mice with SDPDS from the perspective of regulating the level of aquaporin 3 (AQP3). Methods: The model of SDPDS was induced in mice using the multifactor modeling method, which combines internal and external dampness. An artificial climate box was used to create a humid environment, whereas the irregular diet was caused by different feeding methods on odd-even days. The mice were divided into blank control, model group, DL low-dose, DL high-dose, and positive groups. The mice were modeled and treated for 7 day. Levels of gastrin and amylase (AMS) in the serum, mucus secretion in the trachea, and AQP3 in the tissue near the gastric cardia. Results: DL significantly reduced mucus secretion in the trachea (P < 0.001). It also increased the level of AMS in the serum (P < 0.01) and decreased the level of AQP3 in the gastric tissue (P < 0.01). Conclusions: Mice with SDPDS exhibited disturbed water metabolism and significantly increased AQP3 levels. DL can restore the levels of AQP3 and plays an important role in resolving phlegm. This study may also help expand the efficacy of natural drugs containing DL and improve the utilization of natural drug resources.

In this article, a broadband frequency measurement system based on optical spectrum manipulation and stimulated Brillouin scattering (SBS) is proposed and experimentally demonstrated, which can implement wide-range and high-resolution frequency measurement, and generate corresponding broadband interference signals in some frequency bands, that is, it has versatility. Since the frequency range of the pump light to excite SBS is expanded based on the optical spectrum manipulation and high resolution is ensured by the narrow scattering spectrum of SBS, high-resolution spectrum measurement covering a wide frequency band is finally implemented. In addition, the double sideband pump light can be used as the source of electronic interference signal. In the experiments, the frequency measurement range of the proposed system is tested to be 0.03–44 GHz, and the resolution is up to 3 MHz. Furthermore, the frequency measurement and electronic interference sharing the same work band can be carried out in the ranges of 6.3367–7.8367 GHz and 20.36–22.16 GHz.

BackgroundMitochondrial dynamin-related protein 1 (DRP1) regulates mitochondrial division and plays an important role in maintaining hepatocyte function. However, the role of DRP1 in cadmium exposure-induced maternal liver damage in pregnant mice remains unclear. ObjectiveTo investigate the role and mechanism of DRP1 in maternal liver damage induced by cadmium exposure during pregnancy.MethodsThis study consisted of animal experiments and cell experiments. (1) Animal experiments. Mice at 14 days of gestation were randomly divided into three groups: a control group, a low-dose cadmium group (LCd group: 2.5 mg·kg−1), and a high-dose cadmium group (HCd group: 5 mg·kg−1). The pregnant mice were intraperitoneally injected with cadmium chloride (CdCl2) for 6 and 24 h in the next morning. The weights of pregnant mice, uterus, maternal liver, and fetal mice were recorded after sacrifice. Serum and liver of pregnant mice were collected, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, and liver tissues were stained with HE to observe changes in liver function and liver tissue structure. The expressions of oxidative phosphorylation-related proteins, hypoxia inducible factor-1α (HIF-1α) and DRP1 proteins in liver of pregnant mice were detected by Western blotting. (2) Cell experiments. AML12 cells were treated with CdCl2 (10 μmol·L−1) for 0, 2, 6, 12, and 24 h. The expressions of oxidative phosphorylation-related proteins, DRP1, and hypoxia inducible factor-1α (HIF-1α) proteins were detected. AML12 cells were pretreated with DRP1 inhibitor Mdivi-1 for 1 h and then CdCl2 (10 μmol·L−1) for 12 h to detect the expression of oxidative phosphorylation-related proteins and DRP1 protein. AML12 cells were treated with Hif-1α siRNA for 48 h and CdCl2 (10 μmol·L−1) for 6 h to detect the expression of HIF-1α and DRP1 proteins. ResultsThe results of animal experiments showed that cadmium exposure in pregnant mice had no effects on maternal liver weight and liver coefficient. However, the histomorphological changes and necrosis in hepatocytes were observed. Compared with the control group, the serum ALT and AST levels of pregnant mice in the LCd group were significantly increased after 6 h (P＜0.05), and the levels in the HCd group were significantly increased after 6 and 24 h (P＜0.05). Cadmium exposure during pregnancy significantly up-regulated HIF-1α and DRP1 expressions and down-regulated the expressions of oxidative phosphorylation-related proteins in maternal livers. In vitro cell experiments showed that the expressions of oxidative phosphorylation-related proteins was significantly decreased and HIF-1α and DRP1 protein expressions were significantly increased in the AML12 cells treated with CdCl2 for 6 h. Mdivi-1 pretreatment significantly antagonized the inhibitory effect of cadmium on the expressions of oxidative phosphorylation-related proteins in AML12 cells, while Hif-1α siRNA pretreatment significantly antagonized the up-regulative effect of cadmium on DRP1 expression in AML12 cells. ConclusionCadmium exposure in pregnant mice may up-regulate DRP1 expression by activating HIF-1α signaling, then inhibit oxidative phosphorylation level of hepatic cells, and ultimately lead to maternal liver damage.

In the control of the self-driving vehicles, PID controllers are widely used due to their simple structure and good stability. However, in complex self-driving scenarios such as curvature curves, car following, overtaking, etc., it is necessary to ensure the stable control accuracy of the vehicles. Some researchers used fuzzy PID to dynamically change the parameters of PID to ensure that the vehicle control remains in a stable state. It is difficult to ensure the control effect of the fuzzy controller when the size of the domain is not selected properly. This paper designs a variable-domain fuzzy PID intelligent control method based on Q-Learning to make the system robust and adaptable, which is dynamically changed the size of the domain to further ensure the control effect of the vehicle. The variable-domain fuzzy PID algorithm based on Q-Learning takes the error and the error rate of change as input and uses the Q-Learning method to learn the scaling factor online so as to achieve online PID parameters adjustment. The proposed method is verified on the Panosim simulation platform.The experiment shows that the accuracy is improved by 15% compared with the traditional fuzzy PID, which reflects the effectiveness of the algorithm.

This paper presents a novel model predictive current control (MPCC) with an optimum duty-cycle calculation scheme for asymmetrical six-phase permanent magnet synchronous machine (ASPMSM) drives. The proposed method takes advantages of the steady-state performance improvement and the weighting factor elimination. Both merits are owing to the optimum duty-cycle calculation scheme. On the one hand, for the $\alpha $ - $\beta $ subspace, the optimal voltage vector set (VVS) is chosen from twelve ones and the corresponding optimal duty cycles are calculated using the proposed scheme. On the other hand, for the x-y subspace, the VVS can be determined according to that of $\alpha $ - $\beta $ subspace and the optimal duty cycles are deduced using the same scheme. The voltage vector references in two subspaces are then obtained, and they are transformed to six-phase voltages for controlling the six-phase inverter. The proposed method is verified by experimental results based on a 2 kW ASPMSM prototype.

Abstract Background The pre-pregnancy weight and gestational weight gain (GWG) are closely related to perinatal maternal and infant complications, but the relationship between pre-pregnancy weight and GWG and the pattern of interaction have not been reported. This study investigated the influence of weight control during pregnancy on the perinatal maternal and infant outcomes. Methods A total of 835 singleton pregnant women who were hospitalized between January 2018 and December 2018 were retrospectively included in this study and divided into two groups: the diet guidance (DG) group (n = 167) and the control group (n = 668). The pre-pregnancy body mass index (BMI), GWG, and perinatal outcomes of the women and infants were determined in two groups. Results The dietary modification and reasonable exercise during pregnancy effectively reduced the GWG, and even some women with pre-pregnancy obesity achieved weight loss during pregnancy. The GWG in the DG group was significantly lower than in the control group, especially in the second and third trimesters. GWG was positively related to birth weight. The birth weight in the DG group was significantly lower than in the control group when their mothers had similar GWG. In women with pre-pregnancy obesity, GWG seemed to be negatively related to birth weight. However, after adjusting the mean BMI, the pre-pregnancy BMI and GWG were positively related to the birth weight. Compared with the control group, the incidences of dystocia, postpartum hemorrhage, macrosomia, small for gestational age infants and neonatal complications significantly reduced in the DG group, and the preterm birth rate was comparable between two groups. Some women with pre-pregnancy obesity lose weight during pregnancy, but there was no premature birth or small for gestational age infant. The incidences of macrosomia, postpartum hemorrhage, dystocia, cesarean section and gestational diabetes increased significantly with the increase of pre-pregnancy BMI. Conclusion For women with increased pre-pregnancy BMI, strict weight control is required to reduce obesity-related complications of the mother and infant. The weight control in the second and third trimesters is especially important and most likely to prevent GWG. Compared with GWG, pre-pregnancy BMI has greater influence on the birth weight and maternal and infant complications, and may even compromise the benefits of weight control during pregnancy. Thus, weight control is recommended before pregnancy.

Abstract TP73 is expressed as multiple N- and C-terminal isoforms through two separate promoters or alternative splicing. While N-terminal p73 isoforms have been well studied, very little is known about p73 C-terminal isoforms. Thus, CRISPR was used to delete TP73 Exon13 (E13-KO) to induce p73α to p73β isoform switch. We showed that E13-KO led to decreased cell proliferation and migration and sensitized cells to ferroptosis, which can be reverted by knockdown of TAp73β in E13-KO cells. To understand the biological function of p73β in vivo, we generated a mouse model in that the Trp73 E13 was deleted by CRISPR. We showed that p73α to p73β isoform switch led to increased cellular senescence in mouse embryonic fibroblasts. We also showed that E13-deficient mice exhibited shorter life span and were prone to spontaneous tumors, chronic inflammation and liver steatosis as compared to WT mice. Additionally, we found that the incidence of chronic inflammation and liver steatosis was higher in E13-deficient mice than that in Trp73-deficient mice, suggesting that p73β is a strong inducer of inflammatory response. Mechanistically, we showed that TAp73β was able to induce cysteine dioxygenase 1 (CDO-1), leading to cysteine depletion and subsequently, enhanced ferroptosis and growth suppression. Conversely, knockdown of CDO-1 was able to alleviate the growth suppression and ferroptosis in E13-KO cells. Together, our data suggest that at a physiologically relevant level, TAp73β is a strong inducer of growth suppression but insufficient to compensate for loss of TAp73α in tumor suppression due to aberrant induction of inflammatory response and liver steatosis.

2D semiconductors are attracting increasing attention as potentially scalable channels for future transistors, but the scaling of their contact length remains challenging. Here, the authors report the realization of 1D semimetal-2D semiconductor contacts based on individual carbon nanotubes with contact length down to 2 nm.

Abstract An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

Insulin-like growth factors (IGFs) play central roles in the growth and development of vertebrates. Blotched snakehead (Channa maculata), an economically significant fish, exhibits obvious sexual dimorphism and achieves sexual maturity in one year. However, the role of IGFs in C. maculata remains unknown. Three IGF genes were identified in C. maculata, designated as CmIGF1-1, CmIGF1-2, and CmIGF2. The cDNA sequences of these genes are 1184, 655, and 695 bp, encoding putative proteins of 168, 131, and 215 amino acids, respectively, and all three proteins contain a conserved IGF domain. Quantitative real-time PCR (qPCR) revealed the predominant expression of CmIGFs in the liver of adult fish, with higher expression levels observed in males. Notably, CmIGF1-1, CmIGF1-2, and CmIGF2 displayed analogous expression profiles in the liver across various developmental stages, peaking at 365 days after hatching (dah). Subsequently, 600 individuals at 75 dah, at an early developmental stage, were randomly divided equally into six groups and reared in aerated 2 m × 2 m × 2 m cement ponds at 26.0 ± 1.0 °C. Following a one-week acclimatization period, fish without observed abnormalities were intraperitoneally injected with either 17α-ethynylestradiol (EE2) or 17α-methyltestosterone (MT) at a dose of 10 μg/g body weight. Three groups underwent short-term hormone treatment, and the remaining three groups underwent long-term hormone treatment, which included five injections at two-week intervals over ten weeks. The analysis of CmIGFs expression levels in the liver under different hormone treatments revealed that EE2 suppressed the expression of CmIGF1-1 and CmIGF1-2 while promoting CmIGF2 expression. In females, MT up-regulated the expression of CmIGF1-1 and CmIGF2 in a time-dependent manner, but consistently inhibited CmIGF2 expression. In males, MT promoted the expression of CmIGFs in a time-dependent manner, reaching peak levels for CmIGF1-1, CmIGF1-2, and CmIGF2 after 8, 10, and 2 weeks of injection, respectively. Additionally, CmIGF1 and CmIGF2 might exhibit a complementary relationship, with a compensatory increase in CmIGF2 expression in response to low CmIGF1 concentration. These findings highlight the potential key role of IGFs upon growth and their regulation by sex steroid hormones in C. maculata, providing a crucial foundation for future research aimed at elucidating the molecular mechanisms underlying the growth dimorphism between female and male blotched snakeheads.

International terrestrial reference frame (ITRF) input data, generated by Global Navigation Satellite Systems (GNSS), Satellite Laser Ranging (SLR), Very Long Baseline Interferometry (VLBI), and Doppler Orbitography and Radiopositioning integrated by satellite (DORIS) combination centers (CCs), are considered to be relatively high-quality and accurate solutions. Every few years, these input data are submitted to the three ITRS combination centers, namely Institut Géographique National (IGN), Deutsches Geodätisches Forschungsinstitut at the Technische Universität München (DGFI-TUM), and Jet Propulsion Laboratory (JPL), to establish a multi-technique combined terrestrial reference frame (TRF). Generally, these solutions have undergone three rounds of outlier removal: the first at the technique analysis centers during solution generations and the second during the technique-specific combination by the CCs; ITRS CCs then perform a third round of outlier removal and preprocessing during the multi-technique combination of TRFs. However, since the primary objective of CCs is to release the final TRF product, they do not emphasize the publication of analytical preprocessing results, such as the outlier rejection rate. In this paper, our specific focus is on assessing the precision improvement of ITRF input data from 2014 to 2020, which includes evaluating the accuracy of coordinates, the datum accuracy, and the precision of the polar motions, for all four techniques. To achieve the above-mentioned objectives, we independently propose a TRF stacking approach to establish single technical reference frameworks, using software developed by us that is different from the ITRF generation. As a result, roughly 0.5% or less of the SLR observations are identified as outliers, while the ratio of DORIS, GNSS, and VLBI observations are below 1%, around 2%, and ranging from 1% to 1.2%, respectively. It is shown that the consistency between the SLR scale and ITRF has improved, increasing from around −5 mm in ITRF2014 datasets to approximately −1 mm in ITRF2020 datasets. The scale velocity derived from fitting the VLBI scale parameter series with all epochs in ITRF2020 datasets differs by approximately 0.21 mm/year from the velocity obtained by fitting the data up to 2013.75 because of the scale drift of VLBI around 2013. The decreasing standard deviations of the polar motion parameter (XPO, YPO) offsets between Stacking TRFs and 14C04 (20C04) indicate an improvement in the precision of polar motion observations for all four techniques. From the perspective of the weighted root mean square (WRMS) in station coordinates, since the inception of the technique, the station coordinate WRMS of DORIS decreased from 30 mm to 5 mm for X and Y components, and 25 mm to 5 mm for the Z component; SLR WRMS decreased from 20 mm to better than 10 mm (X, Y and Z); GNSS WRMS decreased from 4 mm to 1.5 mm (X and Y) and 5 mm to 2 mm (Z); while VLBI showed no significant change.