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Excessive local accumulation of reactive oxygen species (ROS) in vulvovaginal candidiasis (VVC) leads to oxidative stress and aggravates inflammation. This study aimed to optimize and synthesize four ROS-sensitive polyethylene glycol (PEG)-boride polymers (PB, PCB, BPB, and BCPCB). A nanomicelle (BCPCB-K) was constructed using BCPCB-encapsulated ketoconazole (KTZ). Finally, the depolymerization principle and ROS-sensitive drug release of BCPCB-K as well as its anti-Candida albicans (CA) and therapeutic effects on mice with VVC were explored through in vitro and in vivo experiments. BCPCB-K exhibited low toxicity to mammalian cells in vitro and good biocompatibility in vivo. It also improved the dispersion and solubility of the hydrophobic drug KTZ. Furthermore, BCPCB-K simultaneously scavenged ROS and released the drug, thus facilitating the antifungal and VVC-treating effects of KTZ. Overall, the findings of this study broadened the application of ROS-sensitive materials in the drug-loading and antifungal fields and provided a strategy for VVC treatment.
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Both exogenous and endogenous reactive oxygen species (ROS) in vulvovaginal candidiasis (VVC) play pivotal roles in promoting the hyphal formation of Candida albicans (CA), which suggests that clearing ROS could inhibit CA hyphae formation. A ROS-sensitive hydrogel (CAS@4Arm-PB/CS) was formulated by using a novel four-arm polyethylene glycol (4Arm-PEG) derivative (4Arm-PB) as a crosslinking agent, chitosan (CS) as the hydrogel matrix, and caspofungin (CAS) as the antifungal drug against CA. The ROS-sensitivity, disintegration mechanism, crosslinking action, swelling degree, microstructure, modulus, and rheological properties of 4Arm-PB were characterized. According to the results, 5.0 % 4Arm-PB could quickly and efficiently cross-link 0.5 mg/mL of CS. The ROS-sensitivity of 4Arm-PB was 10-50 µM, indicating a strong ROS sensitivity. The in vitro and in vivo anti-CA results indicated that CAS@4Arm-PB/CS not only cleared endogenous and exogenous ROS and inhibited the formation of CA hyphae and biofilm but also contributed beneficially to the treatment of VVC mice caused by CA infection, implying a certain safety aspect and an in vivo applicability. This research introduces a novel functional crosslinking agent for CS hydrogel formulation, presenting a new avenue for hydrogel-based drug delivery systems and therapeutic strategies for VVC treatment.
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BACKGROUND: The incidence of male breast cancer has been increasing in recent years; however, the long-term survival outcomes of diagnosed patients remain uncertain. This study was designed to evaluate the conditional survival of male breast cancer patients and to predict the future survival of patients through the conditional nomogram, to provide important suggestions for clinical decision-making. METHODS: Retrospective data from the SEER database included 3600 male breast cancer patients, divided into training and validation groups (7â :â 3 ratio). Overall survival rates were calculated using Kaplan-Meier analysis. Conditional survival analysis described survival at specific years. Time-dependent multivariate Cox analysis identified prognostic factors' impact. The conditional survival nomogram model predicted real-time survival rates. RESULTS: Over time, the 5-year real-time survival rate of patients gradually improved, increasing from 70.5 to 74.8, 79.4, 85.8, and 92.9% (respectively, representing 5-year survival rates of 1-4â years after diagnosis). In addition, the improvement in conditional survival rate CS5 showed a nonlinear trend. After 5â years of diagnosis, age, tumor size, and tumor stage had a sustained impact on patient prognosis. Finally, a conditional survival nomogram was constructed to predict the 10-year survival rate in real time. CONCLUSION: Five years after diagnosis, the conditional survival rate of male patients with breast cancer has improved, but it is not nonlinear. In the first 5â years after diagnosis, patients with older age, larger tumor size, poorer tumor stage, and distant metastasis should be actively followed up and treated to improve their long-term survival.
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Purpose: This study aims to translate and validate the Learned Helplessness Scale (LHS) for use in the educational context and specifically among Chinese law school students. Understanding learned helplessness in the context of Chinese law students can provide unique insights into the interaction of legal education, psychological health, and cultural influences, thereby contributing to a more nuanced understanding of learned helplessness. Methods: A total of 711 Chinese college students from two law schools participated in this study. The Learned Helplessness Scale (LHS) was translated into Chinese using forward and backward translation. Exploratory and confirmatory factor analysis, and construct validity were conducted to assess the dimensionality of the Chinese version of the LHS (Chinese LHS). Results: The exploratory factor analysis indicated that the Chinese LHS has a four-factor structure consisting of 14 items, which accounted for 50% of the total variance. The subsequent confirmatory factor analysis further supported this four-factor structure. The internal consistency of the Chinese LHS was found to be medium to high, with Cronbach's α values ranging from 0.63 to 0.87 for the subfactors, and 0.79 for the total scale. In addition, concurrent validity is also confirmed. Conclusion: The 14-item version of the Chinese LHS is a psychometric sound instrument for assessing learned helplessness among Chinese law school students.
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Methoxy poly(ethylene glycol)-block-poly(L-lactide) (MPEG-b-PLLA) has a wide range of applications in pharmaceuticals and biology, and its structure and morphology have been thoroughly studied. In the experiment, we synthesized MPEG-b-PLLA with different block lengths using the principle of ring-opening polymerization by controlling the amount of lactic acid added. The thermodynamic properties of copolymers and the crystallization properties of blends were studied separately. The crystallization kinetics of PDLA/MPEG-b-PLA and PLLA/MPEG-b-PLA composite films were studied using differential scanning calorimetry (DSC). The results indicate that the crystallization kinetics of composite films are closely related to the amount of block addition. The crystallinity of the sample first increases and then decreases with an increase in MPEG-b-PLLA content. These results were also confirmed in polarized optical microscope (POM) and wide-angle X-ray diffraction (WAXD) tests. When 3% MPEG-b-PLLA was added to the PDLA matrix, the blend exhibited the strongest crystallization performance.
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The microreactor could break the limitation of mass transfer and photon transmission in photocatalysis. Through a facile assembly method, a planar photocatalytic microreactor was constructed to fit most of the photocatalysts regardless of their strict preparation method. This microreactor exhibits a 2.41-fold efficiency compared to a bulk reactor. Parameters that affect the photocatalytic performance were discussed in detail by experiment and calculation. The diffusion rate is the main bottleneck in a planar microreactor under a laminar flow. The microreactor with lower height shows higher efficiency owing to faster mass transfer, while the length and width affect slightly. Elevating the light power density provides a diminishing benefit. Faster flow speed reduces the apparent degradation percent but increases the chemical reaction rate, in fact. The reaction rate increases to 9.31 times by reducing the height from 500 to 100 µm and grows another 1.76 times by adding the flow speed from 10 to 40 mL/h. This work illustrates the influence of parameters on planar photocatalytic microreactors and offers a promising prospect for large-volume photocatalytic water treatment.
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Background The paradoxical occurrence of psoriasis triggered by Interleukin-17 (IL-17) inhibitors is notable due to its prominent symptoms and the therapeutic dilemma it presents for follow-up care. Objective To describe cases in our clinic, perform an in-depth literature review, and suggest the most probable mechanisms of action. Method We conducted a literature review on published cases of IL-17 inhibitor-induced psoriasis. Results We found 22 articles reporting 30 cases of IL-17 inhibitor-induced paradoxical psoriasis, primarily observed in patients with a previous psoriasis history. Almost 60% of cases showed a change in lesion morphology, with the plaque or pustular type being prevalent. About 73.3% of patients had to discontinue the implicated drug, leading to partial or complete symptom resolution. The mechanism behind this response seemed to involve IL-17 inhibitors downregulating Tumour Necrosis Factor alpha (TNF-α), subsequently upregulating plasmacytoid dendritic cells and triggering unopposed IFN-alpha (IFN-α) production. Limitation Data are confined to case reports and case series. Conclusion More assertive measures are recommended for treating paradoxical psoriasis induced by IL-17 inhibitors than those caused by TNF-α inhibitors. Reintroducing an IL-17 inhibitor is not advised, as patients did not show improvement.
Subject(s)
Interleukin-17 , Psoriasis , Humans , Psoriasis/chemically induced , Psoriasis/drug therapy , Interleukin-17/antagonists & inhibitors , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic useABSTRACT
By constructing a Ag2O/Bi4O5I2 p-n heterojunction and applying a heat-localization microreactor, efficient photocatalysis enhanced by both photoinduced carrier separation and the photothermal effect was realized. This work focuses on the utilization of near-infrared light to broaden the absorption spectrum and accelerate the transportation of carriers. Through the production and localization of heat, it provides a novel thought for full-spectrum photocatalysis.
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OBJECTIVES: The aim of this study was to investigate the dynamic longitudinal relationship between grip strength and cognitive function. METHODS: 6175 participants aged ≥50 years were included in the study using three waves of follow-up data from the Survey of Health, Ageing, and Retirement in Europe in 2015 (T1), 2017 (T2) and 2019 (T3). Cognitive function was assessed using numeracy, verbal fluency, immediate recall, delayed recall and total. The cross-lagged panel model was used for analysis. RESULTS: There was a correlation between grip strength and cognitive function. Standardized path coefficient from numeracy T1 to grip strength T2 was 0.017 (p = 0.003), and from numeracy T2 to grip strength T3 was 0.014 (p = 0.012). Standardized path coefficient from grip strength T1 to numeracy T2 was 0.096 (p < 0.001), and from grip strength T2 to numeracy T3 was 0.113 (p < 0.001). Other indicators of cognitive function had similar relationships with grip strength. CONCLUSIONS: The study found a statistically significant longitudinal and bidirectional relationship between grip strength and cognitive function in a sample of people aged ≥50 years from several European countries.
Subject(s)
Cognition , Hand Strength , Humans , Hand Strength/physiology , Male , Female , Middle Aged , Europe , Aged , Cognition/physiology , Longitudinal Studies , Aging/physiology , Aging/psychologyABSTRACT
The escalating demand for processed foods has led to the widespread industrial use of glucose isomerase (GI) for high-fructose corn syrup (HFCS) production. This reliance on GIs necessitates continual Co2+ supplementation to sustain high catalytic activity across multiple reaction cycles. In this study, Serratia marcescens GI (SmGI) was immobilized onto surfaces of the metal-organic framework (MOF) material MOF (Co)-525 to generate MOF (Co)-525-GI for use in catalyzing glucose isomerization to generate fructose. Examination of MOF (Co)-525-GI structural features using scanning electron microscopy-energy dispersive spectroscopy, Fourier-transform infrared spectroscopy, and ultraviolet spectroscopy revealed no structural changes after SmGI immobilization and the addition of Co2+. Notably, MOF (Co)-525-GI exhibited optimal catalytic activity at pH 7.5 and 70 °C, with a maximum reaction rate (Vmax) of 37.24 ± 1.91 µM/min and Km value of 46.25 ± 3.03 mM observed. Remarkably, immobilized SmGI exhibited sustained high catalytic activity over multiple cycles without continuous Co2+ infusion, retaining its molecular structure and 96.38% of its initial activity after six reaction cycles. These results underscore the potential of MOF (Co)-525-GI to serve as a safer and more efficient immobilized enzyme technology compared to traditional GI-based food-processing technologies.
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Owing to its unique layered structure, BiOCl demonstrates high photocatalytic activity. However, its wide bandgap hinders the absorption of visible light. Doping modification is an effective method to expand the light absorption edge of photocatalysts by creating a doping energy level within the bandgap. Herein, Co as a variable valence element was used to dope the BiOCl nanosheets through a simple hydrothermal approach. As a result, the absorption edge of Co-BiOCl extends to the visible light region, and the photocatalytic performance was enhanced by 3.02 times. To overcome the shortcoming of photons being consumed easily in the bulk reactor, a planar microreactor was introduced to reduce the attenuation of light and accelerate the mass transfer. By comparison to the bulk reactor, a maximum of 15.3-fold additional activity promotion emerged. This work combines doping modification and reactor improvement to realize highly efficient photocatalysis in practical application.
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Nitrogen, phosphorus and potassium inorganic fertilizers are commonly used when growing apples, but their excessive application has resulted in a decline in soil fertility and therefore an inability to maintain sustainable cultivation systems. It is possible to compensate for this with biofertilizers. Nitrogen-fixing, phosphorus solubilizing, and potassium solubilizing bacteria are biofertilizers with a broad range of possible uses. In this study, beneficial microorganisms were screened from the rhizosphere soil of the apple tree, Malus sieversii (Ldb.) Roem., which is rich in microbial diversity in natural environments. It was essential to investigate their effects on the growth of apple seedlings. Eight populations of organic phosphorus solubilizing bacteria (56), inorganic phosphorus solubilizing bacteria (13), nitrogen-fixing bacteria (22), and potassium solubilizing bacteria (24) were isolated from eight populations of Xinjiang wild apple rhizosphere in Ili by medium culture. Their morphological characteristics were recorded and their activity was determined. The most active strains were Pseudomonas migulae, Pseudomonas poae, and Pseudomonas extremaustralis, which was determined by physiological and biochemical properties and 16S rDNA sequence analysis. The L16 (45) orthogonal experiment, which used the three strains as testing materials, was created to assess the effects of the strains on apple physiological indicators, soil nutrients, leaf nutrients, and biomass, as well as to identify the ideal combination, concentration, timing, and application method. The results indicated that the peroxidase (POD) and catalase (CAT) activities of apple seedlings increased significantly under the 10 treatment, and the (SOD) activities of the 0 (control) and 1 (inorganic fertilizer only) treatments were significantly lower than the other treatments; soluble sugar, soluble protein and chlorophyll contents increased in all treatments compared to 0 and 1, while malondialdehyde and proline contents increased or decreased compared to 0 and 1; apple seedlings in treatment 10 had the highest soil N, P, and K content, leaf N, P, and K content and biomass were also all highest in treatment 10. In summary, the strains screened for the test can be used as biofertilizers and the optimum application was determined for treatment 10, meaning that the results also provide a theoretical basis for their application in artificially grown orchards.
Subject(s)
Malus , Phosphorus , Phosphorus/metabolism , Malus/metabolism , Rhizosphere , Potassium/metabolism , Nitrogen/metabolism , Bacteria/metabolism , Soil/chemistry , Soil MicrobiologyABSTRACT
Objective.This study aimed to develop an automatic and accurate method for severity assessment and localization of coronary artery disease (CAD) based on an optically pumped magnetometer magnetocardiography (MCG) system.Approach.We proposed spatiotemporal features based on the MCG one-dimensional signals, including amplitude, correlation, local binary pattern, and shape features. To estimate the severity of CAD, we classified the stenosis as absence or mild, moderate, or severe cases and extracted a subset of features suitable for assessment. To localize CAD, we classified CAD groups according to the location of the stenosis, including the left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA), and separately extracted a subset of features suitable for determining the three CAD locations.Main results.For CAD severity assessment, a support vector machine (SVM) achieved the best result, with an accuracy of 75.1%, precision of 73.9%, sensitivity of 67.0%, specificity of 88.8%, F1-score of 69.8%, and area under the curve of 0.876. The highest accuracy and corresponding model for determining locations LAD, LCX, and RCA were 94.3% for the SVM, 84.4% for a discriminant analysis model, and 84.9% for the discriminant analysis model.Significance. The developed method enables the implementation of an automated system for severity assessment and localization of CAD. The amplitude and correlation features were key factors for severity assessment and localization. The proposed machine learning method can provide clinicians with an automatic and accurate diagnostic tool for interpreting MCG data related to CAD, possibly promoting clinical acceptance.
Subject(s)
Coronary Artery Disease , Magnetocardiography , Humans , Coronary Artery Disease/diagnostic imaging , Magnetocardiography/methods , Constriction, Pathologic , Machine LearningABSTRACT
Introduction: This longitudinal study aims to investigate the relationship between fear of COVID-19, support-seeking behaviors, and perceived social support among Chinese college students during two distinct periods of the COVID-19 pandemic: the period of strict control (time 1) and the period following a relaxation of restrictions (time 2). Methods: A total of 408 Chinese college students participated in this study. Data collection included demographic information, measures of fear of COVID-19, support-seeking behaviors, and perceived social support. Results: Fear of COVID-19 at time 1 showed a significant positive association with fear of COVID-19 at time 2. The relationship between support-seeking behavior at time 1 and fear of COVID-19 at time 2 was significantly mediated through a chain mediation effect of support-seeking behavior at time 1 and perceived social support at time 2. Discussion: This study contributes to the growing body of evidence on the psychological impacts of the COVID-19 pandemic and underscores the significance of social support in mitigating fear of COVID-19. It calls for a re-evaluation of public health policies considering their potential psychological effects and introduces new opportunities for developing psychosocial interventions.
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Objective To investigate the effect of dexamethasone (DEX) combined with glutamine (Gln) on lung inflammation and pulmonary edema in rats with acute lung injury induced by lipopolysaccharide (LPS) and its related mechanisms. Methods Fifty Wistar rats were randomly divided into control group, model group, dexamethasone group (DEX) and DEX combined with Gln group. Except for the control group, rats in other groups were injected with 6 mg/kg LPS intraperitoneally to induce an acute lung injury. The mRNA expression of p38 MAPK, NLRP3, and NF-κB in lung tissue were detected by real-time quantitative PCR. The protein expressions of p-p38 MAPK, NLRP3, phosphorylated inhibitor of nuclear factor κB (p-IκB), NF-κB p65, aquaporin 1 (AQP1) and AQP5 in lung tissue were detected by Western blot analysis. ELISA was used to detect the content of serum tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 1ß (IL-1ß). Spectrophotometer was employed to detect the content of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in lung tissue. Results Compared with the control group, the lung index of the model group decreased, the content of the serum inflammatory factors TNF-α, IL-6 and IL-1ß significantly increased, and the protein expression of p38 MAPK, NLRP3, NF-κB mRNA, p-p38 MAPK, NLRP3, p-IκB and NF-κB p65 in the lung tissue significantly increased, while that of AQP1, AQP5 decreased, and the content of SOD and GSH-Px in lung tissue decreased, while that of MDA increased; Compared with the model group, the above mentioned symptoms and indicators in each treatment group were significantly improved, among which the DEX combined with Gln group was the most significant. Conclusion DEX combined with Gln can inhibit inflammation, resist oxidative damage, relieve pulmonary edema, and prevent acute lung injury. Its mechanism is related to inhibiting the activation of p38 MAPK, NLRP3, and NF-κB signaling pathways, promoting the expression of AQP1 and AQP5, and promoting the activity of antioxidant products.
Subject(s)
Acute Lung Injury , Pneumonia , Pulmonary Edema , Rats , Animals , Pulmonary Edema/drug therapy , Pulmonary Edema/prevention & control , Pulmonary Edema/metabolism , NF-kappa B/metabolism , Glutamine , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Lipopolysaccharides , Rats, Sprague-Dawley , Rats, Wistar , Acute Lung Injury/chemically induced , I-kappa B Proteins , Dexamethasone/pharmacology , RNA, Messenger , p38 Mitogen-Activated Protein Kinases/metabolism , Superoxide DismutaseABSTRACT
BACKGROUND: Several studies have reported the roles of Trichinella spiralis extracellular vesicles in immune regulation and pathogen diagnosis. Currently, the T. spiralis muscle larvae excretory/secretory product (Ts-ML-ES) is the antigen recommended by the International Commission on Trichinellosis (ICT) for serological diagnosis of trichinellosis. However, it can only be used to detect middle and late stages of infections, and cross-reactions with other parasite detections occur. Therefore, there is a need to identify antigens for specific detection of early stage trichinellosis. METHODS: Extracellular vesicles of T. spiralis muscle larvae (Ts-ML-EVs) were isolated by ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, flow cytometry and western blot. Ts-ML-EVs protein profiles were analyzed by LC-MS/MS proteomics for identification of potential antigens (Ts-TTPA). Ts-TTPA were cloned into pMAL-c5X vector and expressed as recombinant proteins for evaluation of potential as detected antigens by western blot and ELISA. RESULTS: Isolated Ts-ML-EVs were round or elliptic (with diameters between 110.1 and 307.6 nm), showing a bilayer membrane structure. The specific surface markers on the Ts-ML-EVs were CD81, CD63, enolase and the 14-3-3 protein. A total of 53 proteins were identified by LC-MS/MS, including a variety of molecules that have been reported as potential detection and vaccine candidates. The cDNA of Ts-TTPA selected in this study has a total length of 1152 bp, encoding 384 amino acids with a molecular weight of 44.19 kDa. It contains a trypsin domain and can be recognized by anti-His antibody. It reacted with swine sera infected with 10,000 T. spiralis at 15, 25, 35 and 60 days post-infection (dpi). At 10 µg/ml, this antigen could detect T. spiralis antibodies from the swine sera at 13 dpi. There were no cross-reactions with the swine sera infected with other parasites including Clonorchis sinensis, Toxoplasma gondii, Taenia suis, Ascaris suis and Trichuris suis. CONCLUSIONS: This study identifies potential early stage detection antigens and more thoroughly characterizes a serine protease domain-containing protein. Extracellular vesicle proteins may be explored as effective antigens for the early stage detection of trichinellosis.
Subject(s)
Extracellular Vesicles , Swine Diseases , Trichinella spiralis , Trichinella , Trichinellosis , Swine , Animals , Trichinellosis/parasitology , Antigens, Helminth , Helminth Proteins/genetics , Chromatography, Liquid , Tissue Plasminogen Activator , Tandem Mass Spectrometry , Larva/metabolism , Antibodies, Helminth , Swine Diseases/parasitologyABSTRACT
Hindering the recombination of photoinduced electron-hole pairs is of significance for enhancing photocatalytic performance. Applying a voltage to separate carriers offers an option to realize it. Thermoelectric materials own the ability to continuously sustain a voltage when a temperature difference exists between its two sides. However, maintaining the thermoelectric effect without wasting additional energy remains a challenge. Herein, a C3N4/Polyaniline/Poly(vinylidene fluoride) cilia array was fabricated to reach efficient photocatalysis through thermoelectric effect and photothermal effect. The cilia array structure offers more than 40% of light absorbance compared to the film. Hence, the infrared light in sunlight, which was usually omitted in photocatalysis, was transformed into heat. Through the unique design which draws upon the huge difference in thermal conductivity of air and water, a temperature gap was formed between the top and bottom sides of the cilia array by half-submerging it in water. Therefore, the photocatalytic efficiency was improved by 84.4%. This work achieves an energy-saving method to enhance photocatalytic performance by activating thermoelectric effect through infrared light, shedding light on the application of multi-modes enhanced photocatalysis.
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Over the past three decades, its excellent biodegradability and biocompatibility have enabled poly(lactide) (PLA) to be extensively explored as a replacement for oil-based thermoplastics in biomedical and industrial applications. However, PLA homopolymers have "facilitative" limitations such as low mechanical properties, low processing temperatures, slow recrystallization, and insufficient crystallinity, which have usually hindered commercial PLA in industrial and biomedical applications. The formation of stereo-complexation between enantiomeric poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA) chains offers an effective approach to PLA-based engineering materials with improved properties. In this review, we have understandably summarized recent progress in improving the SC crystallization of PLA-based plastics into two aspects, i.e., enantiomeric PLA homopolymers, and enantiomeric PLA-based copolymers. One important point to be noted is that much emphasis is focused on improving SC crystallization by enhancing interactions in the enantiomeric PLA-based copolymers. There is an insightful discussion about the effect of enhanced SC crystallization as well as intermolecular interactions between PLLA and PDLA chains in various stereocomplexable systems. Most importantly, this review starts with the basic understanding of SC crystallization and further elaborates on the rational mechanism of enhanced SC crystallization to provide a broad idea for broadening the road toward PLA-based materials.
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Although immune checkpoint blockade (ICB) therapies have been approved for bladder cancer (BLCA), only a minority of patients respond to these therapies, and there is an urgent need to explore combined therapies. Systematic multi-omics analysis identified S100A5 as a novel immunosuppressive target for BLCA. The expression of S100A5 in malignant cells inhibited CD8+ T cell recruitment by decreasing pro-inflammatory chemokine secretion. Furthermore, S100A5 attenuated effector T cell killing of cancer cells by inhibiting CD8+ T cell proliferation and cytotoxicity. In addition, S100A5 acted as an oncogene, thereby promoting tumor proliferation and invasion. Targeting S100A5 synergized with the efficacy of anti-PD-1 treatment by enhancing infiltration and cytotoxicity of CD8+ T cells in vivo. Clinically, there was a spatially exclusive relationship between S100A5+ tumor cells and CD8+ T cells in tissue microarrays. Moreover, S100A5 negatively correlated with immunotherapy efficacy in our real-world and several public immunotherapy cohorts. In summary, S100A5 shapes a non-inflamed tumor microenvironment in BLCA by inhibiting the secretion of pro-inflammatory chemokines and the recruitment and cytotoxicity of CD8+ T cells. Targeting S100A5 converts cold tumors into hot tumors, thus enhancing the efficacy of ICB therapy in BLCA.
Subject(s)
Carcinoma , Urinary Bladder Neoplasms , Humans , CD8-Positive T-Lymphocytes , Urinary Bladder , Immunotherapy , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/metabolism , Carcinoma/metabolism , Tumor MicroenvironmentABSTRACT
Reverse osmosis (RO) alone has low water recovery efficiency because of membrane fouling and limited operating pressure. In this study, a combined reverse osmosis-forward osmosis (RO-FO) process was used for the first time to improve the water recovery efficiency of secondary effluent in printing and dyeing wastewater. The effects of operating pressure and pH on water recovery and removal efficiency of RO-FO were investigated. The results showed that the optimum conditions were an operating pressure of 1.5 MPa and a feed solution pH of 9.0. Under optimal operating conditions, most of the organic and inorganic substances in the wastewater can be removed, and the rejection of total organic carbon (TOC), Sb, Ca, and K were 98.7, 99.3, 97.0, and 92.7%, respectively. Fluorescence excitation-emission matrices coupled with parallel factor (EEM-PARAFAC) analysis indicated that two components (tryptophan and tyrosine) in the influent were effectively rejected by the hybrid process. The maximum water recovery (Rw, max) could reach 95%, which was higher than the current single RO process (75%). This research provided a feasible strategy to effectively recover water from printing and dyeing wastewater.