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Abstract Background In this prospective cohort study, we determined the phenotypic characteristics of children with regressive autism spectrum disorder (ASD) and explored the effects of rehabilitation. Methods We recruited 370 children with ASD aged 1.5–7 years. Based on the Regression Supplement Form, the children were assigned to two groups: regressive and non-regressive. The core symptoms and neurodevelopmental levels of ASD were assessed before and after 1 year of behavioral intervention using the Autism Diagnostic Observation Schedule (ADOS), Social Response Scale (SRS), Children Autism Rating Scale (CARS), and Gesell Developmental Scale (GDS). Results Among the 370 children with ASD, 28.38% (105/370) experienced regression. Regression was primarily observed in social communication and language skills. Children with regressive ASD exhibited higher SRS and CARS scores and lower GDS scores than those with non-regressive ASD. After 1 year of behavioral intervention, the symptom scale scores significantly decreased for all children with ASD; however, a lesser degree of improvement was observed in children with regressive ASD than in those with non-regressive ASD. In addition, the symptom scores of children with regressive ASD below 4 years old significantly decreased, whereas the scores of those over 4 years old did not significantly improve. Children with regressive ASD showed higher core symptom scores and lower neurodevelopmental levels. Nevertheless, after behavioral intervention, some symptoms exhibited significant improvements in children with regressive ASD under 4 years of age. Conclusion Early intervention should be considered for children with ASD, particularly for those with regressive ASD.

Abstract Solar‐driven CO2 reduction into value‐added C2+ chemical fuels, such as C2H4, is promising in meeting the carbon‐neutral future, yet the performance is usually hindered by the high energy barrier of the C─C coupling process. Here, an efficient and stabilized Cu(I) single atoms‐modified W18O49 nanowires (Cu1/W18O49) photocatalyst with asymmetric Cu─W dual sites is reported for selective photocatalytic CO2 reduction to C2H4. The interconversion between W(V) and W(VI) in W18O49 ensures the stability of Cu(I) during the photocatalytic process. Under light irradiation, the optimal Cu1/W18O49 (3.6‐Cu1/W18O49) catalyst exhibits concurrent high activity and selectivity toward C2H4 production, reaching a corresponding yield rate of 4.9 µmol g−1 h−1 and selectivity as high as 72.8%, respectively. Combined in situ spectroscopies and computational calculations reveal that Cu(I) single atoms stabilize the *CO intermediate, and the asymmetric Cu─W dual sites effectively reduce the energy barrier for the C─C coupling of two neighboring CO intermediates, enabling the highly selective C2H4 generation from CO2 photoreduction. This work demonstrates leveraging stabilized atomically‐dispersed Cu(I) in asymmetric dual‐sites for selective CO2‐to‐C2H4 conversion and can provide new insight into photocatalytic CO2 reduction to other targeted C2+ products through rational construction of active sites for C─C coupling.

BackgroundFew studies have analysed oxaliplatin-induced adverse events (ADEs) in the immune system and skin and subcutaneous tissues through pharmacovigilance. We used this approach to analyse the risk of such ADEs when oxaliplatin combined with immune checkpoint inhibitors (ICIs).MethodsWe evaluated the association between oxaliplatin and ADEs in the immune system and skin and subcutaneous tissues using the reporting odd ratio (ROR) for mining the ADE report signals in the FDA Adverse Event Reporting System database. Risk factors were analyzed using a binary logistic regression analysis using the sex and age of the patients.ResultsThere were 40,474 reports of oxaliplatin as primary suspect drug or second suspect drug. The signal intensities of ADEs such as type II hypersensitivity, type I hypersensitivity, type III immune complex–mediated reaction, anaphylactoid shock and cytokine release syndrome were high in PTs classified by SOC as immune system disorders; in the PTs classified as skin and subcutaneous tissue disorders by SOC, the signal intensities of ADEs such as skin toxicity, skin reaction, rash maculo-papular and skin fissures were higher. In the risk assessment between the two groups, rash showed an increased risk in the oxaliplatin-ICI group, with an OR of 1.96. Nivolumab in combination with oxaliplatin had an OR of 2.196 and an adjusted OR of 2.231. Combined with pembrolizumab, OR was 2.762 and the adjusted OR was 2.678.ConclusionType II hypersensitivity shows a stronger pharmacovigilance signal. Oxaliplatin in combination with nivolumab or pembrolizumab has been shown to increase the risk of rash.

Abstract Background Immune checkpoint inhibitors (ICIs) can improve survivals of metastatic triple negative breast cancer (mTNBC); however, we still seek circulating blood biomarkers to predict the efficacy of ICIs. Materials and methods In this study, we analyzed the data of ICIs treated mTNBC collected in Anhui Medical University affiliated hospitals from 2018 to 2023. The counts of lymphocytes, monocytes, platelets, and ratio indexes (NLR, MLR, PLR) in peripheral blood were investigated via the Kaplan-Meier curves and the Cox proportional-hazards model. Results The total of 50 mTNBC patients were treated with ICIs. High level of peripheral lymphocytes and low level of NLR and MLR at baseline and post the first cycle of ICIs play the predictable role of immunotherapies. Lymphocytes counts (HR = 0.280; 95% CI: 0.095–0.823; p = 0.021) and NLR (HR = 1.150; 95% CI: 1.052–1.257; p = 0.002) are significantly correlated with overall survival. High NLR also increases the risk of disease progression (HR = 2.189; 95% CI:1.085–4.414; p = 0.029). When NLR at baseline ≥ 2.75, the hazard of death (HR = 2.575; 95% CI:1.217–5.447; p = 0.013) and disease progression (HR = 2.189; 95% CI: 1.085–4.414; p = 0.029) significantly rise. HER-2 expression and anti-tumor therapy lines are statistically correlated with survivals. Conclusions Before the initiation of ICIs, enriched peripheral lymphocytes and poor neutrophils and NLR contribute to the prediction of survivals.

Abstract Background Peripheral blood immunomarkers are associated with prognosis in patients with solid tumors receiving chemotherapy or immunotherapy. In this study, the associations of circulating neutrophil‐to‐lymphocyte ratio (NLR), monocyte‐to‐lymphocyte ratio (MLR), and platelet‐to‐lymphocyte ratio (PLR), as well as their dynamic changes were investigated in relation to the efficacy of immunotherapy in patients with primary liver cancer. Methods Comparisons were made between NLR, MLR, and PLR among individuals exhibiting disease control (defined as the best response of partial response [PR] or stable disease [SD]) and those with progressive disease (PD). Additionally, disease control rate (DCR), overall survival (OS), and progression‐free survival (PFS) were compared between individuals with different NLR, MLR, and PLR levels before initiating palliative immunotherapy. Furthermore, comparisons were made between patients with different alterations in the ratios at the second cycle of immunotherapy compared to baseline. These analyses were performed using univariate and multivariate approaches. A total of 119 Chinese patients with liver cancer who underwent immunotherapy were included in this study, which focused on hepatocellular carcinoma (HCC). Results In cases with HCC (n = 104), the cutoffs of NLR, MLR, and PLR to differentiate treatment responders from nonresponders were 3.38, 0.28, and 227.18, respectively. Patients with the best response of PR or SD had significantly lower NLR and MLR. Patients with NLR

ABSTRACT: Protein lactosylation is a significant modification that occurs during the heat treatment of dairy products, causing changes in proteins' physical-chemical and nutritional properties. Knowledge of the detailed lactosylation information on milk proteins under various heat treatments is important for selecting appropriate thermo-processing and identifying markers to monitor heat load in dairy products. In the present study, we used proteomics techniques to investigate lactosylated proteins under different heating temperatures. We observed a total of 123 lactosylated lysines in 65 proteins, with lactosylation even occurring in raw milk. The number of lactosylated lysines and proteins increased moderately at 75°C to 130°C, but dramatically at 140°C. We found that 6 out of 10, 9 out of 16, 6 out of 12, and 5 out of 15 lysine residues in κ-casein, β-lactoglobulin, α-lactalbumin, and αS1-casein, respectively, were lactosylated under the applied heating treatment. Moreover, different lactosylation states of individual lysines and proteins can indicate the intensity of heating processes. Lactosylation of K14 in β-lactoglobulin could distinguish pasteurized and UHT milk, while lactosylation of lactotransferrin can reflect moderate heat treatment of products.

Abstract The water–cement/binder ratio and the admixture of water-reducing agents strongly affect the rheological properties of cement pastes. This study develops mathematical models to predict the apparent viscosity of cement pastes with varying water-cement/binder ratios and polycarboxylate-based superplasticizer content by introducing the power law shear stress-shear strain relation of non-Newtonian fluids into the Navier–Stokes motion equations. The developed models are compared with the results of rheological experiments and verified for their accuracy in simulating the apparent viscosity of cement pastes. These models provide insight into the rheological behaviour of cement pastes and could have practical applications in the construction industry.

Abstract Understanding the CO2 transformation mechanism on materials is essential for the design of efficient electrocatalysts for CO2 reduction. In aconventional adsorbate evolution mechanism (AEM), the catalysts encounter multiple high‐energy barrier steps, especially CO2 activation, limiting the activity and selectivity. Here, lattice carbonate from Cu2(OH)2CO3 is revealed to be a mediator between CO2 molecules and catalyst during CO2 electroreduction by a 13C isotope labeling method, which can bypass the high energy barrier of CO2 activation and strongly enhance the performance. With the lattice carbonate mediated mechanism (LCMM), the Cu2(OH)2CO3 electrode exhibited ten‐fold faradaic efficiency and 15‐fold current density for ethylene production than the Cu2O electrode with AEM at a low overpotential. Theoretical calculations and in situ Raman spectroscopy results show that symmetric vibration of carbonate is precisely enhanced on the catalyst surface with LCMM, leading to faster electron transfer, and lower energy barriers of CO2 activation and carbon–carbon coupling. This work provides a route to develop efficient electrocatalysts for CO2 reduction based on lattice‐mediated mechanism.

Abstract Background An estimated 119,300 new cases of cervical cancer occur annually in China, accounting for 372,00 deaths. Cutaneous metastasis from cervical cancer is a rare event, with an incidence of 0.1–1.3% and typically a preterminal occurrence. Scalp metastasis from cervical cancer is exceptionally anecdotal, with only a dozen examples well documented. Case presentation The patient is a 33-year-old Chinese woman who was diagnosed with International Federation of Gynecology and Obstetrics stage IVB cervical cancer in November 2021. From December 2021 to April 2022, the patient was enrolled in the clinical trial of sintilimab combined with chemotherapy and radiotherapy for treatment of stage IV cervical cancer and underwent six cycles of immunotherapy and chemotherapy (sintilimab plus paclitaxel liposome and cisplatin). Treatment was well tolerated and led to a partial response. The masses adjacent to the spine and iliac bone was largely reduced. Thus, radiotherapy of the metastatic residues was carried out and followed by radiotherapy to the primary tumor at the cervix uteri. However, by the time of the radiotherapy completion in October 2022, the patient noticed painless nodules at the left scapular region and the right hypochondrium. The following month, more nodules occurred on the scalp and trunk, including the left axilla, anterior abdomen, and left back, along with a lesion invading the sternum that caused acute bone pain. The cutaneous masses were white, discrete with a rubbery consistency, and fixed to the skin. Several nodules increased in size and eventually ulcerated. Fine‑needle aspiration cytology of the left back swellings revealed metastatic squamous cell carcinoma, P16 positive. No visceral or brain metastasis was observed at this point. Conclusions Cervical cancer metastases to the scalp are extremely uncommon. When a scalp metastasis is present, it might be the only symptomatic sign of disease progression or widespread metastatic lesions. So far, there is no clear guideline regarding skin metastases treatment. Such skin lesions warrant a thorough radiologic and pathologic workup to form a comprehensive management plan.

Abstract Background Lipopolysaccharide (LPS)-induced dysfunction of pancreatic β-cells leads to impaired insulin (INS) secretion. Astragalus polysaccharide (APS) is a bioactive heteropolysaccharide extracted from Astragalus membranaceus and is a popular Chinese herbal medicine. This study aimed to elucidate the mechanisms by which APS affects INS secretion from β-cells under LPS stress. Methods Rat insulinoma (INS-1) cells were treated with LPS at a low, medium, or high concentration of APS. Glucose-stimulated insulin secretion (GSIS) was evaluated using an enzyme-linked immunosorbent assay (ELISA). Transcriptome sequencing was used to assess genome-wide gene expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to determine the signaling pathways affected by APS. Quantitative reverse transcription–polymerase chain reaction (qRT-PCR) was performed to evaluate the gene expression of glucose transporter 2 (GLUT2), glucokinase (GCK), pancreatic duodenal homeobox-1 (PDX-1), and INS. Western blot analysis was used to detect the protein expression of phosphorylated protein kinase B (p-Akt), total Akt (t-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), total mTOR (t-mTOR), and GLUT2. Results LPS decreased GLUT2, GCK, PDX-1, and INS expression and reduced GSIS. These LPS-induced decreases in gene expression and GSIS were restored by APS treatment. In addition, transcriptome sequencing in combination with KEGG enrichment analysis revealed changes in the INS signaling pathway following APS treatment. LPS decreased p-Akt and p-mTOR expression, which was restored by APS treatment. The restorative effects of APS on GSIS as well as on the expression of GLUT2, GCK, PDX-1, and INS were abolished by treatment with the Akt inhibitor MK2206 or the mTOR inhibitor rapamycin (RPM). Conclusions APS restored GSIS in LPS-stimulated pancreatic β-cells by activating the Akt/mTOR/GLUT2 signaling pathway.

ABSTRACT: Background: The dysregulated long noncoding RNAs (lncRNAs) are implicated in progression of various diseases, including pulpitis. Double homeobox A pseudogene 8 (DUXAP8) has been found to be upregulated in pulpitis. Herein, the functional mechanism of DUXAP8 in lipopolysaccharide (LPS)-induced pulpitis was explored. Material and methods: DUXAP8, microRNA-18b-5p (miR-18b-5p), or hypoxia-inducible factor 3A (HIF3A) levels were examined through reverse transcription-quantitative polymerase chain reaction assay. Cell behaviours were determined by Cell Counting Kit-8 assay for cell viability, Ethynyl-2′-deoxyuridine (EdU) assay for cell proliferation, and flow cytometry for cell apoptosis. Protein levels were measured using western blot. Inflammatory reaction was analysed via enzyme-linked immunosorbent assay. Oxidative stress was assessed by commercial kits. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and pull-down assay were used for validation of interaction between targets. Results: Cell apoptosis, inflammatory reaction, and oxidative stress were induced by LPS in human dental pulp cells (HDPCs). DUXAP8 upregulation and miR-18b-5p downregulation were found in pulpitis. LPS-induced cell injury was relieved after downregulation of DUXAP8. DUXAP8 interacted with miR-18b-5p. The regulation of DUXAP8 was related to miR-18b-5p sponging function in LPS-treated HDPCs. HIF3A served as a target of miR-18b-5p. MiR-18b-5p protected against LPS-induced cell injury through targeting HIF3A. DUXAP8 targeted miR-18b-5p to regulate HIF3A level. Conclusions: Results demonstrated that LPS-induced cell injury in pulpitis was promoted by DUXAP8 through mediating miR-18b-5p/HIF3A axis.

Abstract Background Crop-wild hybridization has generated great concerns since gene flow can be an avenue for transgene escape. However, a rather limited number of studies on risk assessment regarding the dispersion of transgenes from GM soybean to populations of its wild relatives have been previously conducted. Results The results of the 3-year experiment demonstrated that hybrids between GM soybeans and wild soybean had lower seed germination and higher seed productivity than GM soybean. Both of these features of hybrid (especially F2 and F3) were similar to those of wild soybean. Furthermore, the foreign protein was stably expressed in hybrid EPSPS positive plants; however, no difference was observed in agronomic measurements between hybrids that are glyphosate sensitive or resistant, homozygous or heterozygous for the transgene, indicating that the presence of the EPSPS transgene does not affect the vigor of hybrid. In contrast, hybridization between GM soybean and wild soybean may have more impact on hybrid growth and fecundity, this increase in biomass and yield confers a potential competition benefit to hybrids. Conclusions Gene flow from GM soybean to wild soybean has the potential to promote the adaptability of hybrids and may increase the possibility of dispersal of transgenes in wild soybean relatives.

Abstract Renal inflammation and fibrosis are the common pathways leading to progressive chronic kidney disease (CKD). We previously identified hematopoietic cell kinase (HCK) as upregulated in human chronic allograft injury promoting kidney fibrosis; however, the cellular source and molecular mechanisms are unclear. Here, using immunostaining and single cell sequencing data, we show that HCK expression is highly enriched in pro-inflammatory macrophages in diseased kidneys. HCK-knockout (KO) or HCK-inhibitor decreases macrophage M1-like pro-inflammatory polarization, proliferation, and migration in RAW264.7 cells and bone marrow-derived macrophages (BMDM). We identify an interaction between HCK and ATG2A and CBL, two autophagy-related proteins, inhibiting autophagy flux in macrophages. In vivo, both global or myeloid cell specific HCK-KO attenuates renal inflammation and fibrosis with reduces macrophage numbers, pro-inflammatory polarization and migration into unilateral ureteral obstruction (UUO) kidneys and unilateral ischemia reperfusion injury (IRI) models. Finally, we developed a selective boron containing HCK inhibitor which can reduce macrophage pro-inflammatory activity, proliferation, and migration in vitro, and attenuate kidney fibrosis in the UUO mice. The current study elucidates mechanisms downstream of HCK regulating macrophage activation and polarization via autophagy in CKD and identifies that selective HCK inhibitors could be potentially developed as a new therapy for renal fibrosis.

Abstract Vibrational energy harvesters, which can convert mechanical energy distributed widely in the surrounding environment to electrical energy in a convenient, eco‐friendly and sustainable way, have attracted great attention in both academia and industry. In this study, a resilient electret film‐based vibrational energy harvester with a V‐shaped counter electrode is introduced, simulated and constructed. A negatively charged fluorinated polyethylene propylene (FEP) electret film with a wavy shape was adopted in the devices, achieving simultaneously a stable embedded biased voltage and a large tensile deformation during vibration. The influences of the factors on the performance of the device, including the initial stretching state of the resilient electret film, seismic mass and depth of the V‐shape counter electrode, were analyzed comprehensively with finite element simulation and compared to experiments. Further, the structure of the device was optimised for generating a high output power, and a good agreement between the simulation and experimental data was achieved. Additionally, the resonant frequency of the device can be easily tuned between 28 and 68 Hz by merely adjusting the initial stretching state of the wavy FEP electret film, guaranteeing great superiority for broad bandwidth energy harvesting applications. For an optimised energy harvester with a volume of only 15 × 5 × 1.7 mm3 and a tiny seismic mass of 25 mg, and a normalized output power referring to 1 × g (g is the gravity of the Earth) up to 547 μW was obtained at its resonant frequency of 28 Hz. These results demonstrate that such a miniaturised vibrational energy harvester is a promising electrical energy supplier for low‐power‐consumption electronic devices, in particular in wireless sensor networks.

In the realm of cementitious materials, integrating nanoclay shows promise in enhancing properties relevant to additive manufacturing. This paper presents a novel mathematical model that combines simple empirical dissolution/nucleation Avrami-like kinetics with a thixotropic kinetics equation. To analyze the initial exothermic peak, two sets of the calculation parameter function are built to describe the exothermic rate as a function of time, following an exponential pattern. This allows for the prediction of the changes in cumulative heat and heat rate during hydration, considering different concentrations of nanoclay. In the rheological aspect, the relationship between shear stress, shear rate, and time is modeled as a combination of exponential dependencies. This enables the prediction of the variations in shear stress with one variable while holding the other constant (either time or shear rate). By integrating these aspects, this model effectively describes both the first exothermal peak and the rheological behavior during cement hydration with the inclusion of nanoclay. Validated against experimental results, these models demonstrate good accuracy (overall below 3% error), reliability, and applicability. The findings offer valuable insights into the thermal and rheological aspects of concrete printing, enabling informed design decisions for both scientific and industrial applications.

Nonpoint source pollution (NPS) has become the most important reason for the deterioration of water quality, while relevant studies are often limited to African river and lake basins with insufficient data. Taking the Simiyu catchment of the Lake Victoria basin as the study area, we set up a NPS model based on the soil and water assessment tool (SWAT). Furthermore, the rationality of this model is verified with the field-measured data. The results manifest that: (1) the temporal variation of NPS load is consistent with the variation pattern of rainfall, the average monthly output of total nitrogen (TN) and total phosphorus (TP) in the rainy season was 1360.6 t and 336.2 t, respectively, while in the dry season was much lower, only 13.5 t and 3.0 t, respectively; (2) in view of spatial distribution among 32 sub-basins, TN load ranged from 2.051 to 24.288 kg/ha with an average load of 12.940 kg/ha, and TP load ranged from 0.263 to 8.103 kg/ha with an average load of 3.321 kg/ha during the 16-month study period; (3) Among the land use types, the cropland contributed the highest proportion of TN and TP pollution with 50.28% and 76.29%, respectively, while the effect of forest on NPS was minimal with 0.05% and 0.02% for TN and TP, respectively. (4) Moreover, the event mean concentration (EMC) values of different land use types have been derived based on the SWAT model, which are key parameters for the application of the long-term hydrological impact assessment (L-THIA) model. Therefore, this study facilitates applying the L-THIA model to other similar data-deficient catchments in view of its relatively lower data requirement.

Abstract Background We aimed to compare differences in infant feeding patterns (breastfeeding and complementary food supplementation) between children with the autism spectrum disorder (ASD) and typically developing (TD) children through a multicentre study. The relationship between these patterns and later core symptoms and neurodevelopment in children with ASD was also investigated. Methods We analysed breastfeeding and complementary feeding patterns in 1389 children with ASD and 1190 TD children. The Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was used to assess neurodevelopmental levels. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Childhood Autism Rating Scale (CARS), and ASD Warning Behavior Subscale of the CNBS-R2016 were used to assess ASD symptoms. Results Children with ASD had a shorter breastfeeding duration in infancy (8 (3–12) months vs. 10 (6–14) months, P

The space radiation (IR) environment contains high charge and energy (HZE) nuclei emitted from galactic cosmic rays with the ability to overcome current shielding strategies, posing increased IR-induced cardiovascular disease risks for astronauts on prolonged space missions. Little is known about the effect of 5-ion simplified galactic cosmic ray simulation (simGCRsim) exposure on left ventricular (LV) function. Three-month-old, age-matched male Apolipoprotein E (ApoE) null mice were irradiated with 137Cs gamma (γ; 100, 200, and 400 cGy) and simGCRsim (50, 100, 150 cGy all at 500 MeV/nucleon (n)). LV function was assessed using transthoracic echocardiography at early/acute (14 and 28 days) and late/degenerative (365, 440, and 660 days) times post-irradiation. As early as 14 and 28-days post IR, LV systolic function was reduced in both IR groups across all doses. At 14 days post-IR, 150 cGy simGCRsim-IR mice had decreased diastolic wall strain (DWS), suggesting increased myocardial stiffness. This was also observed later in 100 cGy γ-IR mice at 28 days. At later stages, a significant decrease in LV systolic function was observed in the 400 cGy γ-IR mice. Otherwise, there was no difference in the LV systolic function or structure at the remaining time points across the IR groups. We evaluated the expression of genes involved in hemodynamic stress, cardiac remodeling, inflammation, and calcium handling in LVs harvested 28 days post-IR. At 28 days post-IR, there is increased expression of Bnp and Ncx in both IR groups at the lowest doses, suggesting impaired function contributes to hemodynamic stress and altered calcium handling. The expression of Gals3 and β-Mhc were increased in simGCRsim and γ-IR mice respectively, suggesting there may be IR-specific cardiac remodeling. IR groups were modeled to calculate the Relative Biological Effectiveness (RBE) and Radiation Effects Ratio (RER). No lower threshold was determined using the observed dose-response curves. These findings do not exclude the possibility of the existence of a lower IR threshold or the presence of IR-induced cardiovascular disease (CVD) when combined with additional space travel stressors, e.g., microgravity.

Human metapneumovirus (hMPV) causes significant upper and lower respiratory disease in all age groups worldwide. However, there is no licensed drugs or vaccine available against hMPV. γ-Fagarine, an alkaloid isolated from the root of zanthoxylum, has been reported to be effective in the treatment of cancer, inflammatory diseases and antivirals. However, little is known about the inhibitory effect of γ-Fagarine against respiratory virus infection and the mechanism. In this study, we aim to investigate the effect of γ-Fagarine on hMPV infection and explore its underlying molecular mechanisms. Vero-E6 and 16HBE cells were used as cell models. Virus replication and microcosm character were explored in Vero-E6 cells. Then, the antiviral activities were investigated by quantitative real-time PCR (RT-qPCR), western blotting (WB), and indirect immunofluorescence assays (IFAs) in Vero-E6 and 16HBE. Potential mechanisms of γ-Fagarine related to HSPG and lysosome pH were assessed in 16HBE cells. Lastly, a virus-infected mouse model was established and antiviral assay in vivo was conducted. γ-Fagarine showed no toxicity toward Vero-E6 cells and 16HBE cells but demonstrated anti-hMPV activity. Virus titers of γ-Fagarine group were reduced to 33% and 45% of the hMPV groups, respectively. Besides, mechanistic studies revealed that γ-Fagarine could inhibit hMPV by dual mechanisms of direct restraining virus binding with HSPG and influencing lysosome pH. Furthermore, oral delivery of γ-Fagarine to hMPV-infected mice at a dosage of 25 mg/kg reduced the hMPV load in lung tissues. After γ-Fagarine treatment, pathological damage caused by viral infection was also ameliorated. These findings suggest that γ-Fagarine has antiviral effects in vitro and in vivo, which are associated with its ability to restrain virus binding with HSPG and influence lysosome pH, thus indicating that γ-Fagarine has the potential to serve as a candidate to fight against hMPV infection and other respiratory viruses such as influenza viruses and SARS-CoV-2.

ObjectivesThis study analyzed the physical growth of small for gestational age (SGA) and appropriate for gestational age (AGA) twins up to one year after birth.MethodsWeight, length, and head circumference data of 0–1 year-old twins were collected from the Child Health Care System from 2010 to 2019. Physical data were presented as Z-scores. Five parameters – growth level of weight, body length, head circumference, growth velocity, and body proportion (weight for length) were compared in twins.ResultsA total of 3,909 cases were collected (22.61% SGA, 77.39% AGA). 1. In both groups, WAZ (Weight for age z-score), HCZ (Head circumference for age z-score), and LAZ (Length for age z-score) increased more rapidly in the first 6 months. By one year of age, WAZ, HCZ, and LAZ had reached the normal range, but none had reached the average level of normal singleton children. 2. The mean values of WAZ, HCZ, and LAZ in the AGA group were between −1 and 0, and between −2 and − 1 in the SGA group, in the first year after birth. The SGA group lagged significantly behind the AGA group. The LAZ score of SGA and AGA was lower than the WAZ and HCZ scores. 3. The proportion of preterm AGA was the largest in twins, and the growth rate of preterm AGA was the fastest. Preterm twins had greater growth potential than term twins. However, the growth level of preterm SGA was always low. 4. The WFLZ (Weight for length z-score) in each group was approximately close to 0. The WFLZ of SGA was smaller than that of AGA twins at most time points. After 4 months of age, the WFLZ of twins had a downward trend. The WFLZ of preterm SGA approached −1 at approximately 1 year old.ConclusionThe physical growth of SGA and AGA in twins in the first year can reach the normal range but cannot reach the average level of normal singleton children. More attention should be paid to SGA in twins, especially preterm SGA. We should give proper nutritional guidance after 4 months of age to ensure the appropriate body proportion (weight for length) of SGA in twins.Clinical trial registrationwww.chictr.org.cn, CTR2000034761.

Abstract The NF-κB signaling pathway is overactivated in tumor cells, and the activation of the NF-κB signaling pathway releases a large number of inflammatory factors, which enhance tumor immunosuppression and promote tumor metastasis. The cytochrome P450 (CYP450) system consists of important metabolic enzymes present in different tissues and progressive tumors, which may lead to changes in the pharmacological action of drugs in inflammatory diseases such as tumors. In this study, the anticancer effect of tetrahydrocurcumin (THC), an active metabolite of curcumin, on breast cancer cells and the underlying mechanism were investigated. Result showed that THC selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration- and time-dependent manner. Moreover, THC-induced cell apoptosis via a mitochondria-mediated pathway, as indicated by the upregulated ratio of Bax/Bcl-2 and reactive oxygen species (ROS) induction. In addition, THC could affect the CYP450 enzyme metabolic pathway and inhibit the expression of CYP1A1 and activation of the NF-κB pathway, thereby inhibiting the migration and invasion of breast cancer cells. Furthermore, after overexpression of CYP1A1, the inhibitory effects of THC on the proliferation, metastasis, and induction of apoptosis in breast cancer cells were weakened. The knockdown of CYP1A1 significantly enhanced the inhibitory effect of THC on the proliferation, metastasis, and apoptosis induction of breast cancer cells. Notably, THC exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MCF-7 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Collectively, these results showed that TH could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the CYP1A1/NF-κB signaling pathway, indicating that THC serves as a potential candidate drug for the treatment of breast cancer.

Today, most operational dust forecasts extend only 2-5 days. New research finds that the stratosphere exerts long-lasting influence on Saharan dust emission and transport, contributing to subseasonal predictability for dust and air pollution over West Africa and the Eastern Mediterranean.

BackgroundPositive regulators of T cell function play a vital role in the proliferation and differentiation of T cells. However, their functions in gastric cancer have not been explored so far.MethodsThe TCGA-STAD dataset was utilized to perform consensus clustering in order to identify subtypes related to T cell-positive regulators. The prognostic differentially expressed genes of these subtypes were identified using the least absolute shrinkage and selection operator (LASSO) regression analysis. To validate the robustness of the identified signature, verification analyses were conducted across the TCGA-train, TCGA-test, and GEO datasets. Additionally, a nomogram was constructed to enhance the clinical efficacy of this predictive tool. Transwell migration, colony formation, and T cell co-culture assays were used to confirm the function of the signature gene in gastric cancer and its influence on T cell activation.ResultsTwo distinct clusters of gastric cancer, related to T cell-positive regulation, were discovered through the analysis of gene expression. These clusters exhibited notable disparities in terms of survival rates (P = 0.028), immune cell infiltration (P< 0.05), and response to immunotherapy (P< 0.05). Furthermore, a 14-gene signature was developed to classify gastric cancer into low- and high-risk groups, revealing significant differences in survival rates, tumor microenvironment, tumor mutation burden, and drug sensitivity (P< 0.05). Lastly, a comprehensive nomogram model was constructed, incorporating risk factors and various clinical characteristics, to provide an optimal predictive tool. Additionally, an assessment was conducted on the purported molecular functionalities of low- and high-risk gastric cancers. Suppression of DNAAF3 has been observed to diminish the migratory and proliferative capabilities of gastric cancer, as well as attenuate the activation of T cells induced by gastric cancer within the tumor microenvironment.ConclusionWe identified an ideal prognostic signature based on the positive regulators of T cell function in this study.

Abstract Weyl semimetals (WSMs) have attracted great attentions that provide intriguing platforms for exploring fundamental physical phenomena and future topotronics applications. Despite the fact that numerous WSMs are achieved, WSMs with long‐distance distribution of Weyl points (WPs) in given material candidates remain elusive. Here, the emergence of intrinsic ferromagnetic WSMs in BaCrSe2 with the nontrivial nature explicitly confirmed by the Chern number and Fermi arc surface states analysis is theoretically demonstrated. Remarkably, unlike previous WSMs for which opposite chirality WPs are located very close to each other, the WPs of BaCrSe2 host a long‐distance distribution, as much as half of the reciprocal space vector, suggesting that the WPs are highly robust and difficult to be annihilated by perturbations. The presented results not only advance the general understanding of magnetic WSMs but also put forward potential applications in topotronics.

IntroductionGlycosylation is one of the essential post-translational modifications that influences the function of milk proteins.MethodsIn the present study, 998 proteins and 764 glycosylated sites from 402 glycoproteins were identified in human milk by TMT labeling proteomics. Compared to human milk proteins, the glycoproteins were mainly enriched in cell adhesion, proteolysis, and defense/immune process.ResultsThe abundance of 353 glycosylated sites and their 179 parent proteins was quantified. After normalization to their parent protein’s abundance, 78 glycosylated sites in 56 glycoproteins and 10 glycosylated sites in 10 glycoproteins were significantly higher in colostrum and mature milk, respectively. These changed glycoproteins were mainly related to host defense. Intriguingly, one glycosylated site (Asp144) in IgA and two glycosylated sites (Asp38 and Asp1079) in tenascin are significantly upregulated even though their protein abundance was downregulated during lactation.DiscussionThis study helps us figure out the critical glycosylated sites in proteins that might influence their biological function in an unbiased way.

BackgroundPatients with pancreatic duct adenocarcinoma (PDAC) have varied prognoses that depend on numerous variables. However, additional research is required to uncover the latent impact of ubiquitination-related genes (URGs) on determining PDAC patients’ prognoses.MethodsThe URGs clusters were discovered via consensus clustering, and the prognostic differentially expressed genes (DEGs) across clusters were utilized to develop a signature using a least absolute shrinkage and selection operator (LASSO) regression analysis of data from TCGA-PAAD. Verification analyses were conducted across TCGA-PAAD, GSE57495 and ICGC-PACA-AU to show the robustness of the signature. RT-qPCR was used to verify the expression of risk genes. Lastly, we formulated a nomogram to improve the clinical efficacy of our predictive tool.ResultsThe URGs signature, comprised of three genes, was developed and was shown to be highly correlated with the prognoses of PAAD patients. The nomogram was established by combining the URGs signature with clinicopathological characteristics. We discovered that the URGs signature was remarkably superior than other individual predictors (age, grade, T stage, et al). Also, the immune microenvironment analysis indicated that ESTIMATEscore, ImmuneScores, and StromalScores were elevated in the low-risk group. The immune cells that infiltrated the tissues were different between the two groups, as did the expression of immune-related genes.ConclusionThe URGs signature could act as the biomarker of prognosis and selecting appropriate therapeutic drugs for PDAC patients.

Substantial reductions in carbon emissions are necessary to control global warming. However, the low capacity of individual companies to reduce emissions can constrain the capacity of the entire supply chain. This paper investigates how the supply chain manages carbon allowances to rationalize the allocation of carbon allowances and improve supply chain profits. Firstly, the supply chain alone manages the management of carbon quotas and then proposes new management of carbon quotas, including joint management of carbon allowances by manufacturer-led supply chains and co-management of carbon allowances by supplier-led supply chains. The Stackelberg game model aims to find the optimal price, wholesale product price, and carbon reduction level. Then, the paper compares profits under different management models, and the study results show that the supply chain joint management carbon allowance strategy is related to the number of carbon allowances and the price. The results of the study suggest that joint management of carbon allowances by supply chains can promote both environmental benefits and supply chain profitability, but from the perspective of individual benefits, there are not always opportunities for manufacturers and suppliers to join forces; it is also related to the number of carbon allowances and the price of carbon trading, and in some cases, supply chain joining forces will result in the lowest profitability of the whole supply chain. Finally, many numerical experimental validations further show that the joint management of carbon quotas in the supply chain can improve corporate profits and reduce carbon emissions, which provides essential insights for enterprises to manage carbon quotas.

Abstract Background Selenium-binding protein 1 (SELENBP1), a member of the selenium-containing protein family, plays an important role in malignant tumorigenesis and progression. However, it is currently lacking research about relationship between SELENBP1 and immunotherapy in colorectal cancer (CRC). Methods We first analyzed the expression levels of SELENBP1 based on the Cancer Genome Atlas (TCGA), Oncomine andUALCAN. Chisq.test, Fisher.test, Wilcoxon-Mann-Whitney test and logistic regression were used to analyze the relationship of clinical characteristics with SELENBP1 expression. Then Gene ontology/ Kyoto encyclopedia of genes and genomes (GO/KEGG), Gene set enrichment analysis (GSEA) enrichment analysis to clarify bio-processes and signaling pathways. The cBioPortal was used to perform analysis of mutation sites, types, etc. of SELENBP1. In addition, the correlation of SELENBP1 gene with tumor immune infiltration and prognosis was analyzed using ssGSEA, ESTIMATE, tumor immune dysfunction and rejection (TIDE) algorithm and Kaplan-Meier (KM) Plotter database. Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were used to validate the expression of SELENBP1 in CRC samples and matched normal tissues. Immunohistochemistry (IHC) was further performed to detect the expression of SELENBP1 in CRC samples and matched normal tissues. Results We found that SELENBP1 expression was lower in CRC compared to normal colorectal tissue and was associated with poor prognosis. The aggressiveness of CRC increased with decreased SELENBP1 expression. Enrichment analysis showed that the SELENBP1 gene was significantly enriched in several pathways, such as programmed death 1 (PD-1) signaling, signaling by interleukins, TCR signaling, collagen degradation, costimulation by the CD28 family. Decreased expression of SELENBP1 was associated with DNA methylation and mutation. Immune infiltration analysis identified that SELENBP1 expression was closely related to various immune cells and immune chemokines/receptors. With increasing SELENBP1 expression, immune and stromal components in the tumor microenvironment were significantly decreased. SELENBP1 expression in CRC patients affects patient prognosis by influencing tumor immune infiltration. Beside this, SELENBP1 expression is closely related to the sensitivity of chemotherapy and immunotherapy. Conclusions Survival analysis as well as enrichment and immunoassay results suggest that SELENBP1 can be considered as a promising prognostic biomarker for CRC. SELENBP1 expression is closely associated with immune infiltration and immunotherapy. Collectively, our study provided useful information on the oncogenic role of SELENBP1, contributing to further exploring the underlying mechanisms.

Abstract Current research efforts on single-atom catalysts (SACs) exclusively focus on nonmetal or transition-metal atoms as active centers, while employing main-group metal elements is seemingly excluded because their delocalized s/p-bands are prone to yield a broadened resonance for the interaction with adsorbates. Here, we use high-throughput first-principles calculations to investigate the possible incorporation of Mg, Al, and Ga to form graphene-based SACs for NO reduction reaction (NORR) toward NH3. 51 SAC candidates with different metal coordination environments have been computationally screened employing a rationally designed four-step process, yielding six SACs with high catalytic activity and NORR selectivity. The performance is rationalized by the modulation of s/p-band filling of the main-group metals. The adsorption free energy of NO is identified as an efficient descriptor for such SACs. The underlying physical mechanism is revealed and generally applicable to other main group metal SACs. These fundamental insights extend NORR SACs to main-group metal elements.

Abstract Nonsymmorphic symmetries open up horizons of exotic topological boundary states and even generalize the bulk–boundary correspondence, which, however, the third-order topological insulator in electronic materials are still unknown. Here, by means of the symmetry analysis and k · p models, we uncover the emergence of long-awaited third-order topological insulators and the wallpaper fermions in space group I4/mcm (No.140). Based on this, we present the hourglass fermion, fourfold-degenerate Dirac fermion, and Möbius fermion in the (001) surface of Tl4 XTe3 (X = Pb/Sn) with a nonsymmorphic wallpaper group p4g. Remarkably, 16 helical corner states reside on eight corners in Kramers pair, rendering the real electronic material of third-order topological insulators. More importantly, a time-reversal polarized octupole polarization is defined to uncover the nontrivial third-order topology, as is implemented by the 2nd and 3rd order Wilson loop calculations. Our results could considerably broaden the range of wallpaper fermions and lay the foundation for future experimental investigations of third-order topological insulators.

Abstract Background Autism spectrum disorder (ASD) is a group of clinically heterogenic neurodevelopmental disorders, with intellectual disability being one of its common comorbidities. No large-sample, multicenter study has focused on the neurodevelopmental aspect of preschoolers with ASD. This study investigated the neurodevelopmental characteristics of preschoolers with ASD in China and explored the association between them and the core symptoms. Methods We enrolled 1019 ASD preschoolers aged 2–7 years old from 13 cities around China between May 2018 and December 2019, and used the revised Children Neuropsychological and Behavior Scale (CNBS-R2016) to assess their neurodevelopment. Their autistic core behaviors were evaluated based on their Social Responsiveness Scale (SRS), Autism Behavior Checklist (ABC), Child Autism Rating Scale (CARS), and communication warning behavior (CWB) scores in the CNBS-R2016. Results Based on general developmental quotient (GQ) 70%) was found in language and personal-social skills, followed by fine motor skills (68.9%). Gross motor skills had the lowest DD rate (34.0%). We found that fine motor, language, and personal-social developmental quotients (DQs) were significantly lower than gross motor skills in no DD (GQ > 70), mild DD (GQ 55–69), and moderate and below DD groups (GQ ≤ 54). Furthermore, the DQs for language and personal-social skills were significantly lower than for gross and fine motor skills in both DD groups. The ABC, SRS, CARS, and CWB scores in the no DD group were the lowest, moderate in the mild DD group, and highest in the moderate and below DD group. Besides, negative correlations were found between the DQs of the four domains and the ABC, SRS, CARS, and CWB scores, of which the language and personal-social skills DQs had the strongest correlations. Conclusions Preschoolers with ASD had unbalanced neurodevelopment domain patterns and their neurodevelopmental levels were negatively correlated with the autism core symptoms. Hence, pediatricians should actively evaluate the neurodevelopment of children with ASD and conduct long-term follow-up during their early childhood to promote early diagnosis and develop personalized intervention plans. Trial registration ChiCTR2000031194 , registered on 03/23/2020.

Reactive oxygen species play a crucial role in the prognosis and tumor microenvironment (TME) of malignant tumors. An ROS-related signature was constructed in gastric cancer (GC) samples from TCGA database. ROS-related genes were obtained from the Molecular Signatures Database. Consensus clustering was used to establish distinct ROS-related subtypes related to different survival and immune cell infiltration patterns. Sequentially, prognostic genes were identified in the ROS-related subtypes, which were used to identify a stable ROS-related signature that predicted the prognosis of GC. Correlation analysis revealed the significance of immune cell iniltration, immunotherapy, and drug sensitivity in gastric cancers with different risks. The putative molecular mechanisms of the different gastric cancer risks were revealed by functional enrichment analysis. A robust nomogram was established to predict the outcome of each gastric cancer. Finally, we verified the expression of the genes involved in the model using RT-qPCR. In conclusion, the ROS-related signature in this study is a novel and stable biomarker associated with TME and immunotherapy responses.

Background: Xihuang Wan (XHW), a purgative and detoxifying agent, is commonly utilized in modern medicine as a treatment and adjuvant therapy for various malignancies, including breast cancer, liver cancer, and lung cancer. A clinical study demonstrated the potential usefulness of the combination of XHW and gemcitabine as a therapy for pancreatic cancer (PC), indicating that XHW’s broad-spectrum antitumor herbal combination could be beneficial in the treatment of PC. However, the precise therapeutic efficacy of XHW in treating pancreatic cancer remains uncertain.Aim: This study assessed the biological activity of XHW by optimizing the therapeutic concentration of XHW (Xihuang pills, XHP). We performed cell culture and developed an animal test model to determine whether XHP can inhibit pancreatic cancer (PC). We also applied the well-known widely targeted metabolomics analysis and conducted specific experiments to assess the feasibility of our method in PC therapy.Materials and Methods: We used UPLC/Q-TOF-MS to test XHP values to set up therapeutic concentrations for the in vivo test model. SW1990 pancreatic cancer cells were cultured to check the effect the anti-cancer effects of XHP by general in vitro cell analyses including CCK-8, Hoechst 33258, and flow cytometry. To develop the animal model, a solid tumor was subcutaneously formed on a mouse model of PC and assessed by immunohistochemistry and TUNEL apoptosis assay. We also applied the widely targeted metabolomics method following Western blot and RT-PCR to evaluate multiple metabolites to check the therapeutic effect of XHP in our cancer test model.Results: Quantified analysis from UPLC/Q-TOF-MS showed the presence of the following components of XHP: 11-carbonyl-β-acetyl-boswellic acid (AKBA), 11-carbonyl-β-boswellic acid (KBA), 4-methylene-2,8,8-trimethyl-2-vinyl-bicyclo [5.2.0]nonane, and (1S-endo)-2-methyl-3-methylene-2-(4-methyl-3-3-pentenyl)-bicyclo [2.2.1heptane]. The results of the cell culture experiments demonstrated that XHP suppressed the growth of SW1990 PC cells by enhancing apoptosis. The results of the animal model tests also indicated the suppression effect of XHP on tumor growth. Furthermore, the result of the widely targeted metabolomics analysis showed that the steroid hormone biosynthesis metabolic pathway was a critical factor in the anti-PC effect of XHP in the animal model. Moreover, Western blot and RT-PCR analyses revealed XHP downregulated CYP3A4 expression as an applicable targeted therapeutic approach.Conclusion: The results of this study demonstrated the potential of XHP in therapeutic applications in PC. Moreover, the widely targeted metabolomics method revealed CYP3A4 is a potential therapeutic target of XHP in PC control. These findings provide a high level of confidence that XHP significantly acts as a CYP3A4 inhibitor in anti-cancer therapeutic applications.

Abstract Ferroelectrets have promoted a variety of exciting flexible sensors, actuators, and microenergy harvesters. However, most ferroelectrets have been fabricated from non‐degradable petro‐based resins, and thus the recycling of these materials constitutes a big challenge. This article reports biodegradable and bioabsorbable ferroelectret films made from polylactic acid (PLA) resins for highly sensitive transducer applications, which can operate either in piezoelectric 33 or 31/32 mode. By modification of the microstructure and polarization, pronounced longitudinal and transverse piezoelectric activities are realized in a single material. For samples with a thickness of 400 µm and a bulk density of 350 kg m−3, the Young's moduli in thickness and plane direction are ranging from 0.1 to 10 MPa, respectively. After polarization in the thickness direction, quasi‐static piezoelectric d33, g33, d31 (d32), and g31 (g32) coefficients in the PLA films, up to 500 pC N−1, 40 Vm N−1, −44 pC N−1, and −3.6 Vm N−1, are achieved, respectively. The longitudinal piezoelectric coefficients of the PLA films are comparable to non‐degradable polymer ferroelectrets, while the transverse piezoelectric activity is superior, which may be attributed to the reduction of Young's moduli in the plane direction. The preparation procedure of the PLA ferroelectrets is compatible with large‐scale production lines and thus can greatly promote their applications in green electronics.

Indole-3-acetic acid (IAA) and salicylic acid (SA), as critical plant hormones, are involved in multiple physiological regulatory processes of plants. Simultaneous and continuous in vivo detection of IAA and SA will help clarify the mechanisms of their regulation and crosstalk. First, this study reports the development and application of an electrochemical microsensor for simultaneous and continuous in vivo detection of IAA and SA. This electrochemical microsensor system consisted of a tip (length, 2 mm) of platinum wire (diameter, 0.1 mm) modified with carbon cement and multi-walled carbon nanotubes, an untreated tip (length, 2 mm) of platinum wire (diameter, 0.1 mm), as well as a tip (length, 2 mm) of Ag/AgCl wire (diameter, 0.1 mm). It was capable of detecting IAA in the level ranging from 0.1 to 30 µM and SA ranging from 0.1 to 50 µM based on the differential pulse voltammetry or amperometric i-t., respectively. The dynamics of IAA and SA levels in tomato leaf veins under high salinity stress were continuously detected in vivo, and very little damage occurred. Compared to conventional detection methods, the constructed microsensor is not only suitable for continuously detecting IAA and SA in microscopic plant tissue in vivo, it also reduces the damage done to plants during the detection. More importantly, the continuous and dynamic changes in IAA and SA data obtained in stiu through this system not only can help clarify the interaction mechanisms of IAA and SA in plants, it also helps to evaluate the health status of plants, which will promote the development of basic research in botany and precision agriculture.

It is important for food recognition to separate each ingredient within a food image at the pixel level. Most existing research has trained a segmentation network on datasets with pixel-level annotations to achieve food ingredient segmentation. However, preparing such datasets is exceedingly hard and time-consuming. In this paper, we propose a new framework for ingredient segmentation utilizing feature maps of the CNN-based Single-Ingredient Classification Model that is trained on the dataset with image-level annotation. To train this model, we first introduce a standardized biological-based hierarchical ingredient structure and construct a single-ingredient image dataset based on this structure. Then, we build a single-ingredient classification model on this dataset as the backbone of the proposed framework. In this framework, we extract feature maps from the single-ingredient classification model and propose two methods for processing these feature maps for segmenting ingredients in the food images. We introduce five evaluation metrics (IoU, Dice, Purity, Entirety, and Loss of GTs) to assess the performance of ingredient segmentation in terms of ingredient classification. Extensive experiments demonstrate the effectiveness of the proposed method, achieving a mIoU of 0.65, mDice of 0.77, mPurity of 0.83, mEntirety of 0.80, and mLoGTs of 0.06 for the optimal model on the FoodSeg103 dataset. We believe that our approach lays the foundation for subsequent ingredient recognition.

Abstract 2D spontaneous valley polarization attracts great interest both for its fundamental physics and for its potential applications in advanced information technology, but it can only be obtained from inversion asymmetric single-layer crystals, while the possibility to create 2D spontaneous valley polarization from inversion symmetric single-layer lattices remains unknown. Here, starting from inversion symmetric single-layer lattices, a general design principle for realizing 2D spontaneous valley polarization based on van der Waals interaction is mapped out. Using first-principles calculations, we further demonstrate the feasibility of this design principle in a real material of T-FeCl2. More remarkably, such design principle exhibits the additional exotic out-of-plane ferroelectricity, which could manifest many distinctive properties, for example, ferroelectricity-valley coupling and magnetoelectric coupling. The explored design-guideline and phenomena are applicable to a vast family of 2D materials. Our work not only opens up a platform for 2D valleytronic research but also promises the fundamental research of coupling physics in 2D lattices.

IntroductionCellular senescence is a hallmark of tumors and has potential for cancer therapy. Cellular senescence of tumor cells plays a role in tumor progression, and patient prognosis is related to the tumor microenvironment (TME). This study aimed to explore the predictive value of senescence-related genes in thyroid cancer (THCA) and their relationship with the TME.MethodsSenescence-related genes were identified from the Molecular Signatures Database and used to conduct consensus clustering across TCGA-THCA. Differentially expressed genes (DEGs) were identified between the clusters used to perform multivariate Cox regression and least absolute shrinkage and selection operator regression (LASSO) analyses to construct a senescence-related signature. TCGA dataset was randomly divided into training and test datasets to verify the prognostic ability of the signature. Subsequently, the immune cell infiltration pattern, immunotherapy response, and drug sensitivity of the two subtypes were analyzed. Finally, the expression of signature genes was detected across TCGA-THCA and GSE33630 datasets, and further validated by RT-qPCR.ResultsThree senescence clusters were identified based on the expression of 432 senescence-related genes. Then, 23 prognostic DEGs were identified in TCGA dataset. The signature, composed of six genes, showed a significant relationship with survival, immune cell infiltration, clinical characteristics, immune checkpoints, immunotherapy response, and drug sensitivity. Low-risk THCA shows a better prognosis and higher immunotherapy response than high-risk THCA. A nomogram with perfect stability constructed using signature and clinical characteristics can predict the survival of each patient. The validation part demonstrated that ADAMTSL4, DOCK6, FAM111B, and SEMA6B were expressed at higher levels in the tumor tissue, whereas lower expression of MRPS10 and PSMB7 was observed.DiscussionIn conclusion, the senescence-related signature is a promising biomarker for predicting the outcome of THCA and has the potential to guide immunotherapy.

BackgroundIt is well known that the prognosis of Gastric cancer (GC) patient is affected by many factors. However, the latent impact of anoikis on the prognosis of GC patients is insufficient understood.MethodsAccording to the Cancer Genome Atlas (TCGA) database, we elected discrepantly expressed anoikis-related genes (ARGs). Univariate cox and the least absolute shrinkage and selection operator (lasso) analysis were applied to build the ARGs signature. The prognostic effect of the ARGs signature was also evaluated. A series of algorithms were performed to evaluate the discrepancies in the immune microenvironment. Moreover, the correlation between drug sensitivity and ARGs signature was analyzed. We also performed Real-Time Polymerase Chain Reaction (RT-PCR) to probe the signature.ResultsThe ARGs signature of 9 genes was constructed, which was apparently interrelated with the prognosis. The nomogram was established by combining the ARGs signature with clinicopathological characteristics. We found that the predictive power was noteworthily superior to other individual predictors. The immune microenvironment analysis indicated that ESTIMATEscore, ImmuneScores, StromalScores, tumor immune dysfunction and exclusion (TIDE) score were lower in the low-risk group, while immunophenoscore (IPS) was on the contrary. The infiltrated immune cells and immune checkpoint (ICP) expression levels were significantly different between the two groups. Furthermore, nine drugs were positively associated with the ARGs signature score. The results of RT-PCR analysis were consistent with our previous differential expression analysis.ConclusionThe developed ARGs signature could act as the biomarker and provide a momentous reference for Individual therapy of GC patients.

Breast cancer (BC) is one of the most common tumor types and has poor outcomes. In this study, a ubiquitination-related prognostic signature was constructed, and its association with immunotherapy response in BC was explored. A list of ubiquitination-related genes was obtained from the molecular signatures database, and a ubiquitination-related gene signature was obtained by least absolute shrinkage and selection operator Cox regression. The genes, TCN1, DIRAS3, and IZUMO4, had significant influence on BC outcomes. Patients were categorized into two clusters—a high-risk group with poor survival and a low-risk group with greater chances of controlling BC progression. Univariate and multivariate Cox regression analyses revealed that the risk signature was an independent prognostic factor for BC. Gene set enrichment analysis suggested that the high-risk group was enriched in cell cycle and DNA replication pathways. The risk score was positively linked to the tumor microenvironment and negatively correlated with the immunotherapy response. The IC50 values for rapamycin were higher in the low-risk group, whereas those for axitinib, AZD6244, erlotinib, GDC0941, GSK650394, GSK269962A, lapatinib, and PD0325901 were higher in the high-risk group. Therefore, the ubiquitination-related signature is considered a promising tool for predicting a BC patient’s immunotherapy response.

Background: Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders with unclear etiologies. Our recent work indicated that maternal exposure to triclosan (TCS) significantly increased the autistic-like behavior in rats, possibly through disrupting neuronal retinoic acid signaling. Although environmental endocrine disruptors (EEDs) have been associated with autism in humans, the relationship between TCS, one of the EEDs found in antibacterial daily necessities, and autism has received little attention. Objective: The aims of this multicenter study were to evaluate TCS concentrations in typically developing (TD) children and ASD children, and to determine the relationship between TCS levels and the core symptoms of ASD children. Methods: A total of 1345 children with ASD and 1183 TD children were enrolled from 13 cities in China. Ages ranged between 2 and 7 years. A questionnaire was used to investigate the maternal use of antibacterial daily necessities (UADN) during pregnancy. The core symptoms of ASD were evaluated using the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Social Response Scale (SRS), and the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). The TCS concentration was measured using LC-MS/MS. Results: Maternal UADN during pregnancy may be an unrecognized potential environmental risk factor for ASD (OR=1.267, P = 0.023). Maternal UADN during pregnancy strongly correlated with TCS levels in the offspring (Adjusted β = 0.277, P

Abstract Anomalous valley Hall (AVH) effect is a fundamental transport phenomenon in the field of condensed-matter physics. Usually, the research on AVH effect is mainly focused on 2D lattices with ferromagnetic order. Here, by means of model analysis, we present a general design principle for realizing AVH effect in antiferromagnetic monolayers, which involves the introduction of nonuniform potentials to break of PT symmetry. Using first-principles calculations, we further demonstrate this design principle by stacking antiferromagnetic monolayer MnPSe3 on ferroelectric monolayer Sc2CO2 and achieve the AVH effect. The AVH effect can be well controlled by modulating the stacking pattern. In addition, by reversing the ferroelectric polarization of Sc2CO2 via electric field, the AVH effect in monolayer MnPSe3 can be readily switched on or off. The underlying physics are revealed in detail. Our findings open up a new direction of research on exploring AVH effect.

Diamond is of great importance for scientific and practical applications. It is the hardest natural material and holds potential applications in mechanics, electronics and photonics. Over the past few decades, great efforts have been paid for exploring its nature both experimentally and theoretically. Most of the recent studies on diamond are focused on their geometry stability and structural properties, while the research on electronic properties is relatively limited. Here, the recent research advances on diamond from a theoretical perspective are presented. In this mini review, we emphasize the recent breakthroughs related to the geometric and electronic properties of diamond, as well as the promising strategies for tuning their electronic properties, such as doping and constructing heterostructure. We then discuss its potential applications in electronic and optoelectronic devices. Finally, the challenges and opportunities in this field are also provided.

Valley, as a new degree of freedom for electrons, has drawn considerable attention due to its significant potential for encoding and storing information. Lifting the energy degeneracy to achieve valley polarization is necessary for realizing valleytronic devices. Here, on the basis of first-principles calculations, we show that single-layer FeCl2 exhibits a large spontaneous valley polarization (∼101 meV) arising from the broken time-reversal symmetry and spin-orbital coupling, which can be continuously tuned by varying the direction of magnetic crystalline. By employing the perturbation theory, the underlying physical mechanism is unveiled. Moreover, the coupling between valley degree of freedom and ferromagnetic order could generate a spin- and valley-polarized anomalous Hall current in the presence of the in-plane electric field, facilitating its experimental exploration and practical applications.

While solar-to-fuel conversion offers a renewable energy production strategy, photoelectrochemical water splitting requires further optimization. Here, authors examined nitrogen-doped NiFeOx catalysts to improve the oxygen evolution activity and stability of BiVO4 photoanodes.

Abstract Background Mycobacterium chimaera infections subsequent to cardiac surgery are related to contaminated heater-cooler devices, with high mortality. Nevertheless, few studies have been reported in Asia. Case presentation We described the case of a 55-year-old man with Mycobacterium chimaera infection following cardiac surgery in the mainland of China. He was diagnosed with endocarditis caused by Mycobacterium chimaera subsequent to open heart surgery. Metagenomic next-generation sequencing (mNGS) and 16S rRNA gene PCR analysis were used to identify potential pathogens. The patient underwent redo valve replacement surgery and received combination therapy with azithromycin, ethambutol, linezolid, and amikacin. No signs of relapse were observed during the 11-month follow-up visit. Conclusions This is the first documented case of Mycobacterium chimaera infection following cardiac surgery in the mainland of China and the first documented transnational imported case worldwide. Moreover, mNGS is a novel diagnostic technology that can guide antimicrobial therapy prior to obtaining fluid/tissue culture results for Mycobacterium chimaera, providing a new approach for the detection of potential Mycobacterium chimaera infection.

Abstract The intertwined ferroelectricity and band topology will enable the non-volatile control of the topological states, which is of importance for nanoelectrics with low energy costing and high response speed. Nonetheless, the principle to design such system is unclear and the feasible approach to achieve the coexistence of two parameter orders is absent. Here, we propose a general paradigm to design 2D ferroelectric topological insulators by sliding topological multilayers on the basis of first-principles calculations. Taking trilayer Bi2Te3 as a model system, we show that in the van der Waals multilayer based 2D topological insulators, the in-plane and out-of-plane ferroelectricity can be induced through a specific interlayer sliding, to enable the coexistence of ferroelectric and topological orders. The strong coupling of the order parameters renders the topological states sensitive to polarization flip, realizing non-volatile ferroelectric control of topological properties. The revealed design-guideline and ferroelectric-topological coupling not only are useful for the fundamental research of the coupled ferroelectric and topological physics in 2D lattices, but also enable innovative applications in nanodevices.