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Abstract Resorcinol‐formaldehyde (RF) resin represents a promising visible‐light responding photocatalyst for oxygen reduction reaction (ORR) toward H2O2 production. However, its photocatalytic ORR activity toward H2O2 generation is still unsatisfied for practical application. Herein, 3‐hydroxythiophenol‐formaldehyde (3‐HTPF) resin microspheres synthesized through polycondensation reaction between 3‐HTP and formaldehyde at room temperature and subsequent hydrothermal treatment exhibit enhanced photocatalytic ORR activity is reported. The experimental results show that the partial substitution of hydroxy group (─OH) by sulfhydryl one (─SH) through using 3‐HTP to replace resorcinol could slow the rates of nucleation and growth of the resin particles and lead to strongly π‐stacked architecture in 3‐HTPF. The introduction of ─SH group can also improve adsorption ability of 3‐HTPF to O2 molecules and enhance ORR catalytic activity of the photocatalysts. Stronger built‐in electric field, better adsorption ability to O2 molecules, and increased surface catalytic activity collectively boost photocatalytic activity of 3‐HTPF microspheres. As a result, H2O2 production rate of 2010 µm h−1 is achieved over 3‐HTPF microspheres at 273 K, which is 3.4 times larger than that obtained using RF submicrospheres (591 µm h−1). The rational substituent group modulation provides a new strategy for designing polymeric photocatalysts at the molecular level toward high‐efficiency artificial photosynthesis.

Objective: Pyrotinib is a novel irreversible tyrosine kinase inhibitor that has shown efficacy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). This study explored the efficacy and safety of pyrotinib in the treatment of HER2-positive MBC patients in the real world. Methods: From September 2018 to February 2022, 137 female patients with HER2-positive MBC treated in this center were enrolled in this study. The follow-up period ended on January 12, 2023. The primary endpoint of this study was progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), central nervous system (CNS)-PFS, CNS-ORR, CNS-CBR, CNS-DCR, and adverse event (AE) were the secondary endpoints. Results: The ORR, DCR and CBR were 41.98 % (55/131), 87.79 % (115/131) and 44.27 % (58/131) in this cohort, respectively. The median PFS for this cohort was 10.37 months [95 % confidence interval (CI): 9.205-11.535] and the median OS was 37.53 months (not reached). Univariate and multivariate analyses showed that trastuzumab sensitivity was an independent predictor of improved PFS [hazard ratio (HR): 0.579 (0.371-0.904, p=0.016)] and improved OS [0.410 (0.213-0.790, p=0.008)]. Patients treated with a pyrotinib-based regimen as second-line and third-or-post-line therapy had poorer PFS [second-line: 3.315 (1.832-6.000, p

Abstract Hepatocellular carcinoma (HCC) is associated with a poor prognosis. Our previous study demonstrated that Pleomorphic adenoma gene like-2 (PLAGL2) was a potential therapeutic target in HCC. However, the mechanisms that lead to the upregulation of PLAGL2 in HCC remain unclear. The present study revealed that stress-induced epinephrine increased the expression of PLAGL2, thereby promoting the progression of HCC. Furthermore, PLAGL2 knockdown inhibited epinephrine-induced HCC development. Mechanistically, epinephrine upregulated ubiquitin-specific protease 10 (USP10) to stabilize PLAGL2 via the adrenergic β-receptor-2-c-Myc (ADRB2-c-Myc) axis. Furthermore, PLAGL2 acted as a transcriptional regulator of USP10, forming a signaling loop. Taken together, these results reveal that stress-induced epinephrine activates the PLAGL2-USP10 signaling loop to enhance HCC progression. Furthermore, PLAGL2 plays a crucial role in psychological stress-mediated promotion of HCC progression.

The middle and lower reaches of the Yellow River are rich in silt. The Yellow River silt can be utilized as a subgrade filling material along the Yellow River expressway to enhance its resource utilization potential. However, research on the geotechnical mechanical properties of the Yellow River silt is limited. In this study, a series of triaxial shear tests were conducted using the global digital systems triaxial apparatus to examine the effects of initial conditions (confining pressure and relative density) and test conditions (shear rate and drainage conditions) on the static strength and deformation characteristics of the Yellow River silt. The stress–strain curve, volumetric strain curve, envelope of shear strength, stress ratio curve, and internal friction angle distribution under different characteristic states were obtained. The test results showed that the shear strength of the Yellow River silt was more sensitive to confining pressure, relative density, and drainage conditions. The stress–strain curves of the Yellow River silt samples under drained conditions showed a slight strain-softening phenomenon; therefore, there were three characteristic states: peak state, phase transformation state, and critical state. Moreover, the stress–strain curves of the Yellow River silt samples under undrained conditions showed strain hardening characteristics, and there existed three characteristic states: the peak state, critical state, and peak pore pressure state. Additionally, the Yellow River silt samples simultaneously reached the peak and critical states at the end of the shear procedure. Specifically, the strength at the peak and critical states increased with increasing confining pressure and relative density. The shear strength under the undrained conditions was greater than that under the drained conditions. The development of pore pressure under the undrained conditions was in contrast with the dilatancy characteristics under the drained conditions; however, the pore pressure developed more rapidly than that depicted by the dilatancy characteristics. The distribution interval of the friction angle at the characteristic states of the Yellow River silt was between 22.6° and 38.1°. The initial shear modulus and ultimate deviator stress of the Yellow River silt increased with increasing confining pressure and relative density but were not sensitive to the shear rate. The ultimate deviator stress under undrained conditions was greater than that under drained conditions, while the initial shear modulus under drained conditions was smaller than that under undrained conditions under medium–low confining pressure. To strengthen the shear resistance of Yellow River silt, more attention should be paid to improving the compaction degree when the Yellow River silt is used as the filling material of expressway subgrades. This study can provide data and theoretical references for the resource utilization of Yellow River silt in subgrade engineering.

Abstract Background The prognosis of patients with mucinous breast cancer (MuBC) is affected by several factors, but the low incidence of MuBC makes it difficult to conduct extensive and in-depth studies. This study was designed to establish a prognostic model and verify its accuracy in patients with MuBC after chemotherapy and surgery to help develop personalized treatment strategies. Materials and methods Patients with MuBC who underwent chemotherapy and surgery from 2004 to 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. The prognostic factors of patients with MuBC were investigated using a Cox proportional hazards regression analysis. Based on the identified factors, a nomogram was constructed to forecast the overall survival (OS) of patients at 3, 5, and 10 years. Internal (from SEER) and external (from Yunnan Cancer Center, YNCC) verification queues were used to verify the nomogram and demonstrate the predictive capacity of this model. Results The study comprised 1668 MuBC patients from the SEER database and 107 from the YNCC. The nomogram included four characteristics: age, anatomical stage, surgical method, and radiotherapy. The concordance indices in the training, internal verification, and external verification queues were 0.680, 0.768, and 0.864, respectively. The calibration curves for the nomogram showed excellent agreement between the predictions and observations. This nomogram has good clinical application value according to the decision curve analysis. Conclusions The prognosis of patients with MuBC who have undergone chemotherapy and surgery can be forecasted using this nomogram, which would be beneficial to help create individualized treatment plans for the affected patients.

Neighborhood effects are a common strategy for rural households to deal with irrational situations such as deficient information and ability. Based on the 2019 CHFS survey data, we designed a Probit model to verify whether neighborhood effects exist in the online financial investment of rural households. Our paper constructs a multiple mediation model to explore its mechanism. Otherwise, we execute the heterogeneity analysis by dividing the total sample into groups. Our paper proved that (1) Rural households have significant neighborhood effects on online financial investment. (2) Heterogeneity analysis shows that neighborhood effects are stronger among women, the younger, low-education, and low-income rural households. (3) Through the multiple mediation model, we proved that the neighborhood effects on online financial investment of the peasant household work by the financial knowledge spillover and risk-taking enhancement. Our study conduces to a better understanding of the financial decision-making of rural households, which may provide a practical implication for the popularization of new financial products and the optimal design of policy interventions.

BackgroundPrediabetes is associated with an increased risk of cardiovascular diseases and all-cause mortality. Rare research in China has evaluated the prevalence of prediabetes among children and adolescents using the HbA1c criterion or the combined FPG-or-HbA1c diagnostic criterion, and researchers paid no attention to the distributions of blood glucose in Shenzhen, especially for juveniles.MethodsWe conducted a school-based cross-sectional study based on the first-year students from 17 primary, middle, and high schools. Prediabetes was defined as FPG of 5.6–6.9 mmol/L or HbA1c of 5.7%–6.4%. The crude and standardized prevalence of prediabetes with 95% confidence interval (95% CI) was estimated.ResultsA total of 7519 participants, aged 6 to 17 years, were included. For all subjects, the crude prevalence (95% CI) of prediabetes was 1.49% (1.21–1.77), 8.72% (8.08–9.36), and 9.80% (9.13–10.47) by the FPG-only, HbA1c-only, and FPG-or-HbA1c criteria, respectively. Based on the 2010 Shenzhen census population, the standardized prevalence was 1.56% (males 1.85%, females 1.19%), 11.05% (males 11.47%, females 10.53%), and 12.19% (males 13.01%, females 11.15%) by the corresponding criteria. The proportion of prediabetes was higher for males than females, and the prevalence decreased with grade for males but increased for females. The association of BMI and prediabetes was U-shaped curve, indicating higher rates of prediabetes for underweight and obesity people.ConclusionThe blood glucose status of children and adolescents in Shenzhen is worrisome, and the early detection and management of prediabetes are imperative.

Abstract Purpose Invasive micropapillary carcinoma (IMPC) is one of the rare subtypes of breast cancer. This study aimed to explore a predictive nomogram model for IMPC prognosis. Methods A total of 1855 IMPC patients diagnosed after surgery between 2004 and 2014 were identified from the Surveillance, Epidemiology and End Results (SEER) database to build and validate nomogram. A nomogram was created based on univariate and multivariate Cox proportional hazards regression analysis. Receiver operating characteristic (ROC) curves were used to demonstrate the accuracy of the prognostic model. Decision curve analysis (DCA) was performed to evaluate the safety of the model in the range of clinical applications, while calibration curves were used to validate the prediction consistency. Results Cox regression analysis indicated that age ≥62 at diagnosis, negative ER status, and tumor stage were considered adverse independent factors for overall survival (OS), while patients who were married, white or of other races, received chemotherapy or radiotherapy, had a better postoperative prognosis. The nomogram accurately predicted OS with high internal and external validation consistency index (C index) (0.756 and 0.742, respectively). The areas under the ROC curve (AUCs) of the training group were 0.787, 0.774 and 0.764 for 3, 5 and 10 years, respectively, while those of the validation group were 0.756, 0.766 and 0.762, respectively. The results of both DCA and calibration curves demonstrated the good performance of the model. Conclusions A nomogram for IMPC of the breast patients after surgery was developed to estimate 3, 5 and 10 years—OS based on independent risk factors. This model has good accuracy and consistency in predicting prognosis and has clinical application value.

Abstract Purpose The function of stanniocalcin‐1 (STC‐1) in the oncogenesis and progression of tumors has been extensively studied. The purpose of this study was to investigate the relationship between secreted STC‐1 and prognosis in patients with breast cancer (BC) and to determine whether STC‐1 could be a key prognostic factor in BC. Methods The STC‐1 level was measured by ELISA and clinical data from 1210 female patients with BC were used to develop and validate nomograms. We then verified the models through the plotting of ROC curves and calibration curves, calculating the C‐index, and performing decision curve analyses (DCA). Results The level of STC‐1 in the peripheral plasma was significantly correlated with the T stage, N stage, clinical stage, grade, hormone receptors, HER‐2 status, and tumor subtype. Cox regression analyses revealed that estrogen receptor(ER) status, N stage, and STC‐1 level were risk factors for overall survival (OS), whereas T stage, N stage, and STC‐1 level were independent prognostic factors for distant disease‐free survival (DDFS) and disease‐free survival (DFS). Both the ROC curve and the C‐index confirmed the high resolution of these models, while the DCA identified the feasibility of their practical application. In addition, the calibration curves indicated good consistency between the predicted and actual survival rates. Conclusion Nomograms were created based on STC‐1 levels for 3‐, 5‐, and 7‐year OS, DDFS, and DFS of patients with BC respectively. As a key prognostic factor for BC, peripheral blood STC‐1 level can be used clinically as a liquid biopsy indicator.

Up to now, there has been insufficient clinical data to support the safety and effects of vaccination on pregnancy post COVID-19 vaccination. The γδ-T cells are considered an important component in the immune system to fight against viral infection and exhibit critical roles throughout the pregnancy period. However, the immunological roles of γδ-T cells in pregnant women with the COVID-19 vaccination remain unclear. Therefore, the objective of this study is to investigate the alteration of frequency and expression pattern of activation receptors and inhibitory receptors in γδ-T cell and its subsets in peripheral blood samples collected from non-pregnant vaccinated women, vaccinated pregnant women, and unvaccinated pregnant women. Our findings indicated that the frequency of CD3+γδ-T+ cells is lower in vaccinated pregnant women than in unvaccinated pregnant women. But no significant difference was found in the frequency of CD3+γδ-T+ cells between non-pregnant vaccinated women and vaccinated pregnant women. In addition, there were no significant differences in the frequencies of CD3+γδ-T+Vδ1+T cells, CD3+γδ-T+Vδ2+T cells, CD3+γδ-T+Vδ1-Vδ2-T cells, and Vδ1+T cell/Vδ2+T cell ratio between the pregnant women with or without COVID-19 vaccination. Similar results were found after comparing non-pregnant and pregnant women who received the COVID-19 vaccine. However, there was a significant difference in the fraction of Vδ1-Vδ2-T cells in CD3+γδ-T+ cells between non-pregnant vaccinated women and vaccinated pregnant women. The frequency of NKG2D+ cells in Vδ2+T cells was not significantly different in the vaccinated pregnant women when compared to that in unvaccinated pregnant women or non-pregnant vaccinated women. But the percentage of NKG2D+ cells in Vδ1+T cells was the lowest in pregnant women after COVID-19 vaccination. Furthermore, down-regulation of NKP46 and NKP30 were found in Vδ2+T and Vδ1+T cells in the vaccinated pregnant women, respectively. After the vaccination, up-regulation of PD-1 expression in Vδ1+T cells and Vδ2+T cells indicated γδ-T cells could respond to COVID-19 vaccination and display an exhausted phenotype following activation. In conclusion, COVID-19 vaccination influences subtypes of γδ-T cells during pregnancy, but the side effects might be limited. The phenotypical changes of Vδ1+T cells and Vδ2+T cells will be a promising predictor for evaluating the clinical outcome of the COVID-19 vaccine.

Coronary atherosclerotic heart disease (CAD) is a chronic inflammatory cardiovascular disease with high morbidity and mortality. Growing data indicate that many immune cells are involved in the development of atherosclerosis. However, the immunological roles of γδ T cells in the initiation and progression of CAD are not fully understood. Here, we used flow cytometry to determine phenotypical changes of γδ T cells and their subpopulations in peripheral blood samples collected from 37 CAD patients. The Pearson correlation coefficient was used to analyze the relationship between the clinical parameter (serum LDL-C level) and the changes of immunophenotypes of γδ T cells. Our results demonstrated that the frequencies and absolute numbers of total γδ T cells and Vδ2+ T cells were significantly decreased in CAD patients when compared to healthy individuals. However, the proportion of Vδ1+ T cells was much lower in CAD patients than that of healthy individuals. Most importantly, a significant alteration of the Vδ1/Vδ2 ratio was found in CAD patients. In addition, a series of surface markers that are associated with costimulatory signals (CD28, CD40L, CD80, CD86), activation levels (CD69, CD25, HLA-DR), activating NK cell receptors (NKp30, NKp46, NKG2D) and inhibitory receptors (PD-1, CTLA-4, PD-1, Tim-3) were determined and then analyzed in the total γδ T cells, Vδ2+T cells and Vδ2-T cells of CAD patients and healthy individuals. The data demonstrated that immunological activities of total γδ T cells, Vδ2+T cells, and Vδ2-T cells of CAD patients were much lower than those in healthy individuals. Moreover, we found that there were positive correlations between the serum LDL-C levels and frequencies of CD3+γδ+ T cells, CD69+Vδ2+T cells, NKG2D+Vδ2+T cells, and NKp46+Vδ2+T cells. By contrast, there was an inverse correlation between the levels of serum LDL-C and the frequencies of CD69+Vδ2-T cells and NKp46+Vδ2-T cells. Accordingly, these findings could help us to better understand the roles of γδ T cells in the CAD, and shed light on the development of novel diagnostic techniques and therapeutic strategies by targeting γδ T cells for CAD patients.

ObjectiveThe study aimed to analyze the prognostic factors of patients with triple-negative (TN) metaplastic breast carcinoma (MpBC) after surgery and to construct a nomogram for forecasting the 3-, 5-, and 8-year overall survival (OS).MethodsA total of 998 patients extracted from the Surveillance, Epidemiology, and End Results (SEER) database were assigned to either the training or validation group at random in a ratio of 7:3. The clinical characteristics of patients in the training and validation sets were compared, and multivariate Cox regression analysis was used to identify the independent risk variables for the OS of patients with TN MpBC after surgery. These selected parameters were estimated through the Kaplan–Meier (KM) curves using the log-rank test. The nomogram for predicting the OS was constructed and validated by performing the concordance index (C-index), receiver operating characteristics (ROC) curves with area under the receiver operating characteristic curves (AUC), calibration curves, and decision curve analyses (DCAs). Patients were then stratified as high-risk and low-risk, and KM curves were performed.ResultsMultivariate Cox regression analysis indicated that factors including age, marital status, clinical stage at diagnosis, chemotherapy, and regional node status were independent predictors of prognosis in patients with MpBC after surgery. Separate KM curves for the screened variables revealed the same statistical results as with Cox regression analysis. A prediction model was created and virtualized via nomogram based on these findings. For the training and validation cohorts, the C-index of the nomogram was 0.730 and 0.719, respectively. The AUC values of the 3-, 5-, and 8-year OS were 0.758, 0.757, and 0.785 in the training group, and 0.736, 0.735, and 0.736 for 3, 5, and 8 years in the validation group, respectively. The difference in the OS between the real observation and the forecast was quite constant according to the calibration curves. The generated clinical applicability of the nomogram was further demonstrated by the DCA analysis. In all the training and validation sets, the KM curves for the different risk subgroups revealed substantial differences in survival probabilities (P

The WHO’s “Global tuberculosis report 2020” lists tuberculosis (TB) as one of the leading causes of death globally. Existing anti-TB therapy strategies are far from adequate to meet the End TB Strategy goals set for 2035. Therefore, novel anti-TB therapy protocols are urgently needed. Here, we proposed an allogeneic Vγ9Vδ2 T-cell-based immunotherapy strategy and clinically evaluated its safety and efficacy in patients with multidrug-resistant TB (MDR-TB). Eight patients with MDR-TB were recruited in this open-label, single-arm pilot clinical study. Seven of these patients received allogeneic Vγ9Vδ2 T-cell therapy adjunct with anti-TB drugs in all therapy courses. Cells (1 × 108) were infused per treatment every 2 weeks, with 12 courses of cell therapy conducted for each patient, who were then followed up for 6 months to evaluate the safety and efficacy of cell therapy. The eighth patient initially received four courses of cell infusions, followed by eight courses of cell therapy plus anti-MDR-TB drugs. Clinical examinations, including clinical response, routine blood tests and biochemical indicators, chest CT imaging, immune cell surface markers, body weight, and sputum Mycobacterium tuberculosis testing, were conducted. Our study revealed that allogeneic Vγ9Vδ2 T cells are clinically safe for TB therapy. These cells exhibited clinical efficacy in multiple aspects, including promoting the repair of pulmonary lesions, partially improving host immunity, and alleviating M. tuberculosis load in vivo, regardless of their application in the presence or absence of anti-TB drugs. This pilot study opens a new avenue for anti-TB treatment and exhibits allogeneic Vγ9Vδ2 T cells as promising candidates for developing a novel cell drug for TB immunotherapy.Clinical Trial Registration(https://clinicaltrials.gov/ct2/results?cond=&term=NCT03575299&cntry=&state=&city=&dist=) ( NCT03575299).

In the present work, the phase equilibria of the Ni-Ga-Cr ternary system at 850, 1000 and 1150 °C were experimentally investigated to provide the essential data for developing the high-entropy shape memory alloys (HESMAs) containing Ni, Ga and Cr. At 850 °C, in the Ni-rich portion, the B2 phase shows equilibrium with the L12 phase when the Cr content is less than 10.49 at. %, while displaying the equilibrium with L12 and BCC phases when the Cr content increases. The B2 + L12 + BCC changes into B2 + FCC + BCC three-phase equilibria from 850 to 1150 °C, as the L12 phase region becomes narrow with rising temperature. The two-phase equilibrium, B2 + BCC, was found at all the isothermal sections investigated. Other three-phase equilibria were also discovered: B2 + α-Cr3Ga + BCC and Ni2Ga3 + α-Cr3Ga + L at 850 °C, and B2 + α-Cr3Ga + L at 1000 °C. Significantly, an athermal ω intermetallic compound with the space group of P3¯m1 was observed distributing at the B2 phase in the quenched Ni45.98-Ga25.50-Cr28.52, Ni42.23-Ga15.70-Cr42.07 and Ni16.54-Ga13.63-Cr69.83 (at. %) alloys after being annealed at 1150 °C for 10 days. The high-resolution transmission electron microscopy (HRTEM) results reveal that the ω shows a crystallographic orientation of [11¯0]B2//[112¯0]ω; (111)B2//(0001)ω with the B2 parent phase.

Coronary atherosclerotic heart disease (CAD) is a chronic inflammatory cardiovascular disease with high morbidity and mortality. Growing data indicate that many immune cells are involved in the development of atherosclerosis. However, the immunological roles of gd T cells in the initiation and progression of CAD are not fully understood. Here, we used flow cytometry to determine phenotypical changes of gd T cells and their subpopulations in peripheral blood samples collected from 37 CAD patients. The Pearson correlation coefficient was used to analyze the relationship between the clinical parameter (serum LDL-C level) and the changes of immunophenotypes of gd T cells. Our results demonstrated that the frequencies and absolute numbers of total gd T cells and Vd2+ T cells were significantly decreased in CAD patients when compared to healthy individuals. However, the proportion of Vd1+ T cells was much lower in CAD patients than that of healthy individuals. Most importantly, a significant alteration of the Vd1/Vd2 ratio was found in CAD patients. In addition, a series of surface markers that are associated with costimulatory signals (CD28, CD40L, CD80, CD86), activation levels (CD69, CD25, HLA-DR), activating NK cell receptors (NKp30, NKp46, NKG2D) and inhibitory receptors (PD-1, CTLA-4, PD-1, Tim-3) were determined and then analyzed in the total gd T cells, Vd2+ T cells and Vd2- T cells of CAD patients and healthy individuals. The data demonstrated that immunological activities of total gd T cells, Vd2+ T cells, and Vd2- T cells of CAD patients were much lower than those in healthy individuals. Moreover, we found that there were positive correlations between the serum LDLC levels and frequencies of CD3+ gd+ T cells, CD69+ Vd2+ T cells, NKG2D+ Vd2+ T cells, and NKp46+ Vd2+ T cells. By contrast, there was an inverse correlation between the levels of serumLDL-C and the frequencies of CD69+ Vd2- T cells and NKp46+ Vd2- T cells. Accordingly, these findings could help us to better understand the roles of gd T cells in the CAD, and shed light on the development of novel diagnostic techniques and therapeutic strategies by targeting gd T cells for CAD patients. [ABSTRACT FROM AUTHOR]

Deferasirox is the firsHine drug for iron overload due to thalassemia in adults and pediatric patients It is classified as a 如 e II compound in the Biopharmaceutics Classfication System, and thus the partide size of its active pharmaceutical ing-edient (API) should be strictly controlled during the manufacturing process. In the present stud% laser diffraction was adopted to measure the particle size distribution of deferasirox API. We also developed and validated an accurate and convenient method ty investigating important optical parameters and sample dispersing conditions. The relative standard deviation values, namely d(0.1), d(0.5), d(0.9), and d (4,3), measured via methodology validation and actual sample measurement were < 3%. The & ssdution curves of several batches of dispersble tablets prepared using deferasirox with difFerent particle sizes were compared in the four dissolved media to investigate the influence of particle size on drug dissolution in vitro. Results indicated that the partide size distribution of deferasirox API significantly affected the release of its dispersible tablet. [ABSTRACT FROM AUTHOR]