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Abstract Eukaryotic cytochrome P450 enzymes, generally colocalizing with their redox partner cytochrome P450 reductase (CPR) on the cytoplasmic surface of organelle membranes, often perform poorly in prokaryotic cells, whether expressed with CPR as a tandem chimera or free-floating individuals, causing a low titer of heterologous chemicals. To improve their biosynthetic performance in Escherichia coli, here, we architecturally design self-assembled alternatives of eukaryotic P450 system using reconstructed P450 and CPR, and create a set of N-termini-bridged P450-CPR heterodimers as the counterparts of eukaryotic P450 system with N-terminus-guided colocalization. The covalent counterparts show superior and robust biosynthetic performance, and the N-termini-bridged architecture is validated to improve the biosynthetic performance of both plant and human P450 systems. Furthermore, the architectural configuration of protein assemblies has an inherent effect on the biosynthetic performance of N-termini-bridged P450-CPR heterodimers. The results suggest that spatial architecture-guided protein assembly could serve as an efficient strategy for improving the biosynthetic performance of protein complexes, particularly those related to eukaryotic membranes, in prokaryotic and even eukaryotic hosts.

Abstract Background Currently, there is a lack of biomarkers to identify breast cancer (BC) patients who would benefit from CDK4/6 inhibitors. This study combined machine learning (ML) algorithms based on transcriptomic data with both in vivo and in vitro experiments to identify therapeutic efficacy-related biomarkers of the CDK4/6 inhibitor ribociclib from the perspective of long non-coding RNA (lncRNA). Methods We used the Genomics of Drug Sensitivity in Cancer database along with the “oncoPredict” algorithm to calculate the half maximal inhibitory concentration (IC50) values for ribociclib based on transcriptome data. ML algorithms were utilized to select key lncRNAs related to ribociclib and to establish a model which could be used for selection of potential beneficiaries of ribociclib. Cellular experiments were conducted to validate the ML analysis and explore the potential biological mechanisms by which RERE-AS1 influences ribociclib efficacy and malignant phenotype of BC cells. Correlation analysis with clinical pathological factors, RT-qPCR experiments on tissue specimens, and pan-cancer analysis were carried out to explore the expression pattern, and the prognostic and diagnostic potential of RERE-AS1 in cancers. Results We have identified 11 key ribociclib-related lncRNAs and constructed an artificial neural network model (ANNM) based on lncRNA. Cellular experiments demonstrated that overexpression of RERE-AS1 promoted the anti-tumor activity of ribociclib in BC cells. Furthermore, RERE-AS1 is crucial in suppressing the malignant traits of BC cells through the reduction of MEK and ERK phosphorylation levels. Patients with smaller primary tumors and lower pathological stage exhibited higher levels of RERE-AS1 expression. Lastly, a pan-cancer analysis revealed that RERE-AS1 exhibits distinctly abnormal expression patterns, prognostic significance, and clinical diagnostic value in BC, compared to other cancers. Conclusions The ANNM established through ML algorithms can serve as predictive indicators for the efficacy of ribociclib in BC patients. LncRNA RERE-AS1, a newly discovered biomarker, holds significant promise for diagnosis, treatment, and enhancing the therapeutic response to ribociclib in BC. Graphical Abstract

Abstract Acid mine drainage (AMD), characterized by its acidity and high content of heavy metals, is a significant global environmental problem that harms human health through its impact on rivers. Therefore, this study aims to identify heavy metals in both surface and underground AMD-polluted karst rivers, focusing on the Zhijin River area which is severely affected by AMD, and assess their health risks to residents. Through the collection of 30 surface water samples and 16 groundwater samples from both wet and dry seasons, the study examines the concentration, sources of pollution, and health implications of six heavy metals (Fe, Mn, Cr, Cd, As, and Hg). The results showed that Fe and Mn levels in surface water were highly polluted during both seasons, especially during the wet season, with Fe levels reaching 20.0 mg/L and Mn levels reaching 1.9 mg/L. Further correlation and principal component analyses revealed that mining activities are the primary contributors to the contamination in this region. Health risk assessments and Monte Carlo simulation, including both deterministic and probabilistic, showed that the noncarcinogenic health risk indices for surface water and groundwater were within acceptable limits for both seasons. However, groundwater poses a higher carcinogenic risk to children, with As levels during the wet season and Cr levels during the dry season warranting close monitoring. Factors such as body weight and intake rate played a crucial role in health risk evaluations. This study underscores the need for further attention to groundwater risk, temporal heterogeneity in the Zhijin River.

Objective To explore the factors that affect the coordinated development of blood banks and apheresis plasma collection banks (hereinafter referred to as plasma banks), and explore feasible measures for the coordinated development of blood banks and plasma banks. Methods The blood information management system and blood source information management system were used to retrieve related data of blood and plasma donation from 9 cities in Shandong province from 2017 to 2021. The number of blood donors and plasma donors and the intersection of them were analyzed. The data analysis was performed using chi-square test, and a questionnaire survey was conducted to investigate the policies and information status, as well as expectations for coordinated development for blood and plasma donation. Results From 2017 to 2021, the total number of blood donors in 9 cities was higher than that of plasma donors, both have been increasing year by year, and the increase in plasma donors was significantly higher than that of blood donors (131.78% vs 23.90%, P

Post-translational modification (PTM) plays a crucial role in adaptation of mammals to environmental changes, enabling them to survive in stressful situations. One such PTM is SUMO modification, which is evolutionarily conserved. It involves the covalent and reversible attachment of a small ubiquitin-like modifier (SUMO) to lysine (Lys) residues in the target protein. SUMOylation regulates various functions, including cell proliferation, differentiation, apoptosis, senescence, and maintenance of specific cellular activities. It achieves this by influencing protein-protein interactions, subcellular localization, protein stability, and DNA binding activity. Mounting evidence suggests that SUMOylation is implicated in the pathogenesis of metabolic disorders such as obesity, insulin resistance, and fatty liver. This review aims to provide an overview of the role of SUMOylation in regulating tissue adaptation to metabolic stress. Recent advancements in spectroscopic techniques have shed light on potential targets of SUMOylation and the underlying regulatory mechanisms have been elucidated, laying the theoretical foundation for the development of targeted SUMOylation interventions for metabolic syndrome while minimizing side effects.

Abstract Introduction Recent data have shown elevated infection rates in several subpopulations at risk of SARS-CoV-2 infection and COVID-19, including immunocompromised (IC) individuals. Previous research suggests that IC persons have reduced risks of hospitalization and medically attended COVID-19 with two doses of mRNA-1273 (SpikeVax; Moderna) compared to two doses of BNT162b2 (Comirnaty; Pfizer/BioNTech). The main objective of this retrospective cohort study was to compare real-world effectiveness of third doses of mRNA-1273 versus BNT162b2 at multiple time points on occurrence of COVID-19 hospitalization and medically attended COVID-19 among IC adults in the United States (US). Methods This retrospective, observational comparative effectiveness study identified patients from the US HealthVerity database from December 11, 2020, through August 31, 2022. Medically attended SARS-CoV-2 infections and hospitalizations were assessed following a three-dose mRNA-1273 versus BNT162b2 regimen. Inverse probability weighting was applied to balance baseline confounders between vaccine groups. Relative risk (RR) and risk difference were calculated for subgroup and sensitivity analyses using a non-parametric method. Results In propensity score-adjusted analyses, receiving mRNA-1273 vs. BNT162b2 as third dose was associated with 32.4% (relative risk 0.676; 95% confidence interval 0.506–0.887), 29.3% (0.707; 0.573–0.858), and 23.4% (0.766; 0.626–0.927) lower risk of COVID-19 hospitalization after 90, 180, and 270 days, respectively. Corresponding reductions in medically attended COVID-19 were 8.4% (0.916; 0.860–0.976), 6.4% (0.936; 0.895–0.978), and 2.4% (0.976; 0.935–1.017), respectively. Conclusions Our findings suggest a third dose of mRNA-1273 is more effective than a third dose of BNT162b2 in preventing COVID-19 hospitalization and breakthrough medically attended COVID-19 among IC adults in the US.

BackgroundAcute cadmium (Cd) exposure can cause damage to multiple tissues, with the kidney being the primary target organ. The development of Cd-induced acute kidney injury involves complex mechanisms, in which autophagy and oxidative stress play crucial roles.ObjectiveTo investigate the effect of 10-hydroxy-2-decenoic acid (10-HDA) on kidney injury in mice exposed to cadmium, and provide experimental basis for studying the pathogenesis and prevention of Cd poisoning.MethodsThirty-five male C57BL/6 mice were divided into 7 groups (each of 5 mice): control group (normal saline, intraperitoneal injection), CdCl2 group (4 mg·kg−1, intraperitoneal injection), intervention groups ( 4 mg·kg−1 CdCl2, intraperitoneal Injection + 50, 100, 150, or 200 mg·kg−1 10-HDA, oral gavage), and 10-HDA group (150 mg·kg−1, oral gavage). All treatments were given for 14 d. Twenty-four hours after the last infection, physiological indicators [blood urea nitrogen (BUN), creatinine (CRE), malondialdehyde (MDA), and superoxide dismutase (SOD)], histopathological indicators, autophagy-related proteins (Atg7, Atg5, Beclin-1, and LC3), and mitochondrial autophagy-related proteins (PINK1 and Parkin) were detected to examine the effect of 10-HDA on kidney injury caused by CdCl2.ResultsCompared with the control group, the body weight of mice in the CdCl2 group was significantly reduced (P

Abstract Background Triangular fibrocartilage complex (TFCC) injury is a frequent soft tissue injury that has been observed to accompany distal radius fractures (DRFs) with concomitant changes in radiologic parameters. The aim of this study was to investigate the relevance of distal radial radiologic parameters associated with DRF and traumatic TFCC injury. Methods A total of 172 patients with distal radius fractures who underwent X-ray, CT, and MRI before undergoing volar locking plate or external splint fixation between October 2021 and December 2022 were included in this study. An analysis of various radiologic parameters and the classification of fracture type and TFCC injuries by CT and MRI was performed. All patients were divided into the TFCC uninjured group and the injured group. The incidence and relevant radiologic parameters were compared. Results This study included 76 males and 96 females with a mean age of 56.1 years. Among all patients, 33 (19.2%), 40 (23.2%), and 99 (57.6%) had DRF with A, B, and C fractures, respectively, according to the AO/OTA classification. In patients with fractures, the TFCC was found to be injured in 54.1% (93/172) of patients (type 1A in 21, 1B in 46, 1C in 39, and 1D in 35) but uninjured in 45.9% (79/172). There were significant differences between the TFCC injured and uninjured groups regarding the radius length (p = 0.044) and DRUJ distance (p = 0.040) of radiologic parameters that changed with DRF, although there were no differences between the two groups regarding gender, age, injured side, intra- and extra-articular, radius inclination and palmer tilt angle, or sagittal translation. Within the TFCC injured group, the radius length and DRUJ distance were 4.83 mm and 2.95 mm less or wider than 7.19 mm and 1.83 mm of the uninjured group. Moreover, shorter radius length was related to type lB TFCC injury (p = 0.041). Both radius length (AUC = 0.658) and DRUJ distance (AUC = 0.582) had no convincing predictive value for TFCC injury in DRF. Conclusion 1B TFCC injury is most common in patients with DRF and concomitant TFCC injury. Both radius length and DRUJ distance have a significant statistical correlation with TFCC injury, and patients with TFCC injury tend to have a shortened radius and wider DRUJ distance, although they have no predictive value for TFCC injury in DRF. In addition, a shorter radius length was related to type lB TFCC injury.

Abstract Background Alveolar bone defects, particularly palatal bone dehiscence (PBD) and labial bone fenestration (LBF), occur frequently as a result of retraction of the maxillary anterior teeth. The study aims to explore the long-term bone remodeling of maxillary anterior teeth in adult patients with post-orthodontic treatment PBD and LBF. Materials and methods The study includes 24 adult patients with maxillary protrusion (8 males, 16 females) who were treated with extraction of four first premolars and had alveolar bone defects (PBD or LBF) in maxillary anterior teeth following orthodontic treatment. Cone-beam computed tomography imaging measurements were obtained before (T1), after (T2) orthodontic treatment, and after at least 1-year removable thermoplastic retainer retention (T3). The maxillary anterior teeth with PBD or LBF at T2 were divided into the PBD or LBF groups, respectively. The labial and palatal alveolar bone height (ABH), alveolar bone thickness (ABT), and movement of maxillary anterior teeth were measured during retraction (T2–T1) and retention (T3–T2) periods. Results The incidence of PBD and LBF in maxillary anterior teeth significantly increased after orthodontic treatment and decreased during the retention period. In the PBD group, the palatal ABH of all maxillary anterior teeth significantly increased from T1 to T2 but decreased from T2 to T3. The ABT of the maxillary central incisor and canine significantly increased on the palatal side and decreased on the labial side during the retention period. In the LBF group, the labial ABT of the maxillary central incisor at the apical level showed a significant decrease from T1 to T2, followed by an increase from T2 to T3. In both groups, the maxillary central incisor showed significant labial movement, with a relative intrusion during the retention period. Conclusion For adult patients with maxillary protrusion, the alveolar bone defect of maxillary anterior teeth caused by orthodontic retraction significantly improved during the retention period, indicating good long-term bone remodeling. Our findings suggest that a combination of spontaneous reorientation of maxillary anterior teeth and bone remodeling contributed to alveolar bone covering in these patients.

Previous research has established a positive link between prosocial behavior (PB) and psychological well-being. However, limited studies have explored the relationship between PB and well-being (WB), particularly among vocational students. Furthermore, the underlying mechanisms, including mediating factors, remain understudied in this context. This study aimed to investigate the association between PB and WB among vocational students while examining the mediating role of basic psychological needs. A sample of 221 vocational students (mean age = 19.68 years, SD = 1.57) completed anonymous questionnaires assessing PB, basic psychological needs, and WB. The results revealed a positive correlation between PB and WB in vocational students (r = 0.22, p < 0.01), with basic psychological needs partially mediating this relationship (β = 0.14, t = 10.85, p < 0.001, 95% CI = (0.18, 0.23)). These findings enhance our understanding of the association between PB and vocational students’ WB, shed light on the mechanisms involved, and offer insights into promoting the well-being of vocational students.

Addressing the challenges of significant speed overshoot, stability issues, and system oscillations associated with the sliding mode control (SMC) strategy in maximum power point tracking (MPPT) for permanent magnet synchronous wind power systems, this paper introduces a fuzzy sliding mode control (FSMC) method employing an innovative exponential convergence law. By incorporating a velocity adjustment function into the traditional exponential convergence law, a novel convergence law was designed to mitigate oscillations during the sliding phase and expedite the convergence rate. Additionally, a fuzzy controller was developed to implement a fuzzy adaptive SMC strategy, optimizing the MPPT for permanent magnet synchronous wind power generation systems. Simulation results indicated that this approach offered a faster response and superior interference rejection capabilities, compared to conventional and modified SMC strategies. The improved FSMC strategy demonstrated a swift, dynamic response and excellent steady-state performance, improving the efficiency of MPPT, thus confirming the effectiveness of the proposed method.

Scheduling decisions for concurrent emergency response (CER) across multiple disaster sites presents numerous difficulties. The main challenge is to minimize human casualties while taking into account the rationality of resource allocation across different disaster sites. This paper establishes a joint scheduling model for emergency vehicles on freeways in the context of CER. The model aims to minimize the transportation time, dispatch cost, and casualty risk, by using the resource site scheduling scheme as the decision variable, addressing multiple disaster and resource sites. Specifically, a casualty risk function based on the rescue waiting time was designed to balance the competing needs among various disaster sites, enhance equitable resource allocation, and reduce the probability of casualties. To achieve global convergence in a high-dimensional solution space, a tailored heuristic algorithm called adaptive dual evolutionary particle swarm optimization (ADEPSO) is proposed. The numerical results show that the scheduling scheme proposed by the ADEPSO algorithm satisfies all constraints and demonstrates significant advantages in large-sized instances. Compared to the two basic algorithms, ADEPSO provides a more cost-effective scheme and reduces the average rescue waiting time. Moreover, integrating the casualty risk function significantly decreases the average rescue waiting time at both high- and low-priority disaster sites, thereby directly lowering the casualty risk.

Abstract Background The group care is a well-established maternal care model that has been widely used in many developed countries, but in China, it is confined to prenatal care services. In addition, affected by traditional birth culture, Chinese women tend to focus more on their fetuses and newborns but lack attention to their own intrapartum and postpartum care. The aim of this study was to construct and implement a prenatal, intrapartum, and the postpartum continuous group care model that combines online and offline service in Hainan Province, China, and to evaluate the effect on maternal women and newborns. Methods This study was a randomized controlled trial involving 144 pregnant women in a first-class tertiary general hospital in Hainan Province, China. Women were divided into an intervention group and a control group using the random number table, with 72 women in each group. The control group received routine maternal care services, and the intervention group received the continuous group care based on the routine maternal care services. Count data such as rate of cesarean section and incidence rate of fetal macrosomia were analyzed with the chi-square test or Fisher’s exact test, and the General Self-efficacy Scale scores were analyzed by repeated measures ANOVA. P 0.05). Conclusion The continuous group care with online and offline service can effectively control the gestational weight gain, reduce the rate of cesarean section, macrosomia, and postpartum depression. It can improve the self-efficacy of women and the rate of exclusive breastfeeding effectively. Trial registration Chinese Clinical Trial Regestry (ChiCTR2200065765, 04/11/2022, Retrospectively registered).

Summary: Neuroblastoma is the most common extracranial solid tumor of childhood. While MYCN and mutant anaplastic lymphoma kinase (ALKF1174L) cooperate in tumorigenesis, how ALK contributes to tumor formation remains unclear. Here, we used a human stem cell-based model of neuroblastoma. Mis-expression of ALKF1174L and MYCN resulted in shorter latency compared to MYCN alone. MYCN tumors resembled adrenergic, while ALK/MYCN tumors resembled mesenchymal, neuroblastoma. Transcriptomic analysis revealed enrichment in focal adhesion signaling, particularly the extracellular matrix genes POSTN and FN1 in ALK/MYCN tumors. Patients with ALK-mutant tumors similarly demonstrated elevated levels of POSTN and FN1. Knockdown of POSTN, but not FN1, delayed adhesion and suppressed proliferation of ALK/MYCN tumors. Furthermore, loss of POSTN reduced ALK-dependent activation of WNT signaling. Reciprocally, inhibition of the WNT pathway reduced expression of POSTN and growth of ALK/MYCN tumor cells. Thus, ALK drives neuroblastoma in part through a feedforward loop between POSTN and WNT signaling.

Background: Low-dose ionizing radiation-induced protection and damage are of great significance among radiation workers. We aimed to study the role of glutathione S-transferase Pi (GSTP1) in low-dose ionizing radiation damage and clarify the impact of ionizing radiation on the biological activities of cells. Results: In this study, we collected peripheral blood samples from healthy adults and workers engaged in radiation and radiotherapy and detected the expression of GSTP1 by qPCR. We utilized γ-rays emitted from uranium tailings as a radiation source, with a dose rate of 14 μGy/h. GM12878 cells subjected to this radiation for 7, 14, 21, and 28 days received total doses of 2.4, 4.7, 7.1, and 9.4 mGy, respectively. Subsequent analyses, including flow cytometry, MTS, and other assays, were performed to assess the ionizing radiation’s effects on cellular biological functions. In peripheral blood samples collected from healthy adults and radiologic technologist working in a hospital, we observed a decreased expression of GSTP1 mRNA in radiation personnel compared to the healthy controls. In cultured GM12878 cells exposed to low-dose ionizing radiation from uranium tailings, we noted significant changes in cell morphology, suppression of proliferation, delay in cell cycle progression, and increased apoptosis. These effects were partially reversed by overexpression of GSTP1. Moreover, low-dose ionizing radiation increased GSTP1 gene methylation and downregulated GSTP1 expression. Furthermore, low-dose ionizing radiation affected the expression of GSTP1-related signaling molecules. Conclusions: This study shows that low-dose ionizing radiation damages GM12878 cells and affects their proliferation, cell cycle progression, and apoptosis. In addition, GSTP1 plays a modulating role under low-dose ionizing radiation damage conditions. Low-dose ionizing radiation affects the expression of Nrf2, JNK, and other signaling molecules through GSTP1.

Abstract Background Previous studies have reported inconsistent effects of premolar extraction on the oropharynx and hyoid bones. Currently, no strong evidence is available regarding the effect of extraction on upper airway size. Hence, the aim of this study was to analyse the effects of first premolar extraction on the oropharynx and hyoid bone positions in female adult patients, and further explored differences in oropharynx and hyoid bone changes among skeletal patterns. Methods The study population included 40 female adult patients who did not undergo extraction and 120 female adult patients who underwent extraction of four premolars; the including patients had four distinct sagittal and vertical skeletal patterns. Cone-beam computed tomography was performed before (T0) and after (T1) orthodontic treatment. Eight oropharynx variables and five hyoid bone variables were measured using Dolphin 3D Imaging software. Paired and independent t-tests were used to analyse measurements between timepoints and groups, respectively. Results The oropharynx volume increased significantly in the extraction group; changes did not differ significantly between extraction and non-extraction groups. Oropharynx variables did not differ significantly at T0 among the four skeletal pattern groups. After orthodontic extraction treatment, the oropharynx volume increased significantly in the class I-norm and class I-hyper subgroups, but not in the class II-norm and class II-hyper subgroups. Significant increases were observed in the oropharynx volume and most constricted axial area from T0 to T1 in the moderate retraction group, but not in the maximum retraction group. Extraction patients exhibited significant posterior movement of the hyoid, particularly among maximum retraction patients. Conclusions In female adult patients, first premolar extraction tends to increase the oropharynx size and cause posterior movement of the hyoid bone, particularly in skeletal class I patients. For skeletal class II and hyperdivergent patients with a narrow oropharynx, first premolar extraction does not negatively influence oropharynx size or hyoid bone position. The differences of oropharyngeal changes between moderate retraction patients and maximum retraction patients were not significant.

High drug loading improves therapeutic efficacy and reduces side effects in drug delivery. Here, the authors use controlled diffusion of solvents to precipitate drug nanoparticles in polymer particles while the polymer is solidifying and demonstrate the particles for drug delivery in a spinal cord injury model.

The summer hypoxia off the Changjiang Estuary is one of the largest coastal hypoxic systems in the world and has displayed spatial heterogeneity in recent years. Based on observation data in the summer of 2014, hypoxia was identified both in the bottom and mid-layers. Except for the typical bottom hypoxia in the submarine canyon, the subsurface oxygen minima (SOM) were captured in the mid-layer of 10~15 m, with lower dissolved oxygen in the mid-layer than at the bottom (30–50 m). This SOM phenomenon was located in the lower boundary of the pycnocline and above the Taiwan warm current (TWC) and Kuroshio subsurface water (KSSW). Due to the southern expansion of Changjiang diluted water (CDW), a high phytoplankton biomass (the maximum chlorophyll a of 25 μg L−1, pH of 8.6, and DO of 11 mg L−1) band occupied the surface area along 123°E. By analyzing the 24-h continuous observation and high-resolution profile data, we revealed that the subsurface oxygen minima were predominantly controlled by remineralization and bottom-flushing effects. Fast local consumption occurred near the pycnocline layer, while the lateral transport of oxygen-rich ambient water replenished the bottom oxygen deficit from south to north. We summarize and contextualize three hot spots of hypoxia into a conceptual diagram and emphasize the influences of advection, mixing, and respiration on their location and severity. Overall, compared with the discussion about the low DO background of TWC/KSSW, this research highlights the flushing effects of TWC/KSSW that will reshape the hypoxia structure and alleviate the hypoxia severity in the south hypoxia area off the Changjiang Estuary.

The slope shape has a significant effect on the surface stress state of slope, and the stress state is closely related to the slope stability. The previous rainfall infiltration model only takes the slope with straight line shape into account, and did not include the slope with curve shape. Combining Mein-Larson infiltration model with slope shape function, the infiltration function of concave slope under rainfall is deduced. Combined with limit equilibrium analysis method, a calculation model of concave slope stability is proposed. At the same time, according to the idea of slope shape fitting and slope shape simplification, the actual slope is studied as concave slope and straight slope respectively. The results show that the infiltration depth of wetting front has a linear relationship with rainfall time, and the wetting front is paralleled to the slope at different rainfall time. When the actual slope is analyzed as a concave slope, the rainfall infiltration law is more in line with the actual situation; when the rainfall time is 10 days, the calculation result of the shallow slope model is 0.95, while the stability coefficients of the calculation model and the numerical simulation are 1.004 and 1.003 respectively, and the relative error is not more than 1%. Therefore, compared with the previous calculation model, this model not only takes the actual slope shape into account, but also has the characteristics of simple calculation and high reliability.

First-principles calculations of multi-component alloys have been studied in detail. Herein, the first-principles calculations of Mg-5Zn-0.5Al-xSn alloys were performed by using the virtual crystal approximation (VCA) method. By calculating the lattice constants and elastic constants of the Mg-5Zn-0.5Al-xSn doping models, it was found that the mechanical properties and micro-hardness were related with the content of Sn. With the increase of Sn content, and the best ductility and the smallest micro-hardness were achieved at Sn = 2 wt.%. To verify the calculation results, the Mg-5Zn-0.5Al-xSn alloys were prepared and micro-hardness and tensile tests were conducted. The experiments demonstrate that the trends in mechanical properties obtained from the experiments are in agreement with the VCA computational results. These findings indicate that the VCA method has guiding significance in industries for rapid screening of high-performance Mg alloys.

Normalizing the tumor microenvironment (TME) is a potential strategy to improve the effectiveness of immunotherapy. Vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β pathways play an important role in the development and function of the TME, contributing to the immunosuppressive status of TME. To inhibit VEGF and/or TGF-β pathways can restore TME from immunosuppressive to immune-supportive status and enhance sensitivity to immunotherapy such as programmed death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors. In this review, we described the existing preclinical and clinical evidence supporting the use of anti-VEGF and/or anti-TGF-β therapies to enhance cancer immunotherapy. Encouragingly, adopting anti-VEGF and/or anti-TGF-β therapies as a combination treatment with anti-PD-(L)1 therapy have been demonstrated as effective and tolerable in several solid tumors in clinical trials. Although several questions need to be solved, the clinical value of this combination strategy is worthy to be studied further.

Macrobenthos have been used to monitor the self-pollution of cage culture. Will cage culture inevitably reduce their biomass and biodiversity? A one-year investigation was conducted in a lagoon with a history of cage culture for approximately 20 years. In December, the macrobenthos biomass in cage culture area (CCA) was higher than that in FTA (area farthest from CCA). The macrobenthos biodiversity in CCA and NCA (area near CCA) was higher. During the production period, the stabilities of the microbenthic communities in NCA and FRA (area further from CCA) were lower. In the nonproduction period, the stability of the macrobenthic community in CCA was higher than that in FTA. The landform, fishing and organic matter and Ex-P (exchangeable phosphorus) in sediments jointly affected macrobenthos. Cage culture did not inevitably reduce macrobenthos biomass and biodiversity but provided stable microhabitats for macrobenthos. The NCA and FRA may be ecotones between CCA and FTA.

Abstract Background Pulmonary arterial smooth muscle cell (PASMC) proliferation plays a crucial role in hypoxia-induced pulmonary hypertension (HPH). Previous studies have found that resistin-like molecule β (RELM-β) is upregulated de novo in response to hypoxia in cultured human PASMCs (hPASMCs). RELM-β has been reported to promote hPASMC proliferation and is involved in pulmonary vascular remodeling in patients with PAH. However, the expression pattern, effects, and mechanisms of action of RELM-β in HPH remain unclear. Methods We assessed the expression pattern, mitogenetic effect, and mechanism of action of RELM-β in a rat HPH model and in hPASMCs. Results Overexpression of RELM-β caused hemodynamic changes in a rat model of HPH similar to those induced by chronic hypoxia, including increased mean right ventricular systolic pressure (mRVSP), right ventricular hypertrophy index (RVHI) and thickening of small pulmonary arterioles. Knockdown of RELM-β partially blocked the increases in mRVSP, RVHI, and vascular remodeling induced by hypoxia. The phosphorylation levels of the PI3K, Akt, mTOR, PKC, and MAPK proteins were significantly up- or downregulated by RELM-β gene overexpression or silencing, respectively. Recombinant RELM-β protein increased the intracellular Ca2+ concentration in primary cultured hPASMCs and promoted hPASMC proliferation. The mitogenic effects of RELM-β on hPASMCs and the phosphorylation of PI3K, Akt, mTOR, PKC, and MAPK were suppressed by a Ca2+ inhibitor. Conclusions Our findings suggest that RELM-β acts as a cytokine-like growth factor in the development of HPH and that the effects of RELM-β are likely to be mediated by the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK pathways.