Clinical characteristics and prognosis of patients with newly diagnosed primary central nervous system lymphoma: a multicentre retrospective analysis.

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

Prohibitin 1 inhibits cell proliferation and induces apoptosis via the p53-mediated mitochondrial pathway in vitro.

BACKGROUND: Prohibitin 1 (PHB1) has been identified as an antiproliferative protein that is highly conserved and ubiquitously expressed, and it participates in a variety of essential cellular functions, including apoptosis, cell cycle regulation, proliferation, and survival. Emerging evidence indicates that PHB1 may play an important role in the progression of hepatocellular carcinoma (HCC). However, the role of PHB1 in HCC is controversial. AIM: To investigate the effects of PHB1 on the proliferation and apoptosis of human HCC cells and the relevant mechanisms in vitro. METHODS: HCC patients and healthy individuals were enrolled in this study according to the inclusion and exclusion criteria; then, PHB1 levels in the sera and liver tissues of these participates were determined using ELISA, RT-PCR, and immunohistochemistry. Human HepG2 and SMMC-7721 cells were transfected with the pEGFP-PHB1 plasmid and PHB1-specific shRNA (shRNA-PHB1) for 24-72 h. Cell proliferation was analysed with an MTT assay. Cell cycle progression and apoptosis were analysed using flow cytometry (FACS). The mRNA and protein expression levels of the cell cycle-related molecules p21, Cyclin A2, Cyclin E1, and CDK2 and the cell apoptosis-related molecules cytochrome C (Cyt C), p53, Bcl-2, Bax, caspase 3, and caspase 9 were measured by real-time PCR and Western blot, respectively. RESULTS: Decreased levels of PHB1 were found in the sera and liver tissues of HCC patients compared to those of healthy individuals, and decreased PHB1 was positively correlated with low differentiation, TNM stage III-IV, and alpha-fetoprotein ≥ 400 µg/L. Overexpression of PHB1 significantly inhibited human HCC cell proliferation in a time-dependent manner. FACS revealed that the overexpression of PHB1 arrested HCC cells in the G0/G1 phase of the cell cycle and induced apoptosis. The proportion of cells in the G0/G1 phase was significantly increased and the proportion of cells in the S phase was decreased in HepG2 cells that were transfected with pEGFP-PHB1 compared with untreated control and empty vector-transfected cells. The percentage of apoptotic HepG2 cells that were transfected with pEGFP-PHB1 was 15.41% ± 1.06%, which was significantly greater than that of apoptotic control cells (3.65% ± 0.85%, P < 0.01) and empty vector-transfected cells (4.21% ± 0.52%, P < 0.01). Similar results were obtained with SMMC-7721 cells. Furthermore, the mRNA and protein expression levels of p53, p21, Bax, caspase 3, and caspase 9 were increased while the mRNA and protein expression levels of Cyclin A2, Cyclin E1, CDK2, and Bcl-2 were decreased when PHB1 was overexpressed in human HCC cells. However, when PHB1 was upregulated in human HCC cells, Cyt C expression levels were increased in the cytosol and decreased in the mitochondria, which indicated that Cyt C had been released into the cytosol. Conversely, these effects were reversed when PHB1 was knocked down. CONCLUSION: PHB1 inhibits human HCC cell viability by arresting the cell cycle and inducing cell apoptosis via activation of the p53-mediated mitochondrial pathway.

Investigation and analysis of magnetic resonance imaging experience and psychological status of patients.

OBJECTIVE: To analyze factors influencing the service experience of magnetic resonance imaging (MRI) examination and psychological status of patients admitted to a hospital and propose targeted solutions, and optimize the examination process and nursing by analyzing the MRI examination experience and psychological effect on patients. METHODS: The MRI examination rooms of two tertiary general hospitals in Haikou City were sampled at random, and 206 patients who met the study criteria were surveyed on site. RESULTS: (1) The item with the lowest mean score for patient examination services was whether earplugs were provided to the patient during the examination (B8 = 0.47). (2) Environmental logistics experience (16.83 ± 3.036) received the lowest score among the three service experience dimensions. (3) The average anxiety score of the patients was 5.38. (4) There was a positive correlation between the examination experience and the examination service experience of the patients. (5) Patients with higher monthly income had decreased anxiety (coefficient = -2.334), and MRI examination of the extremities relieved the anxiety (coefficient = -4.782). CONCLUSION: The environmental logistics factors, poor service attitude, examination site, and income were the most significant factors affecting the MRI examination experience and psychological status of patients, which can be improved by providing information, enhancing the waiting environment, providing targeted patient education, and evaluating the experience immediately.

miR-200a-3p inhibits the PDGF-BB-induced proliferation of VSMCs by affecting their phenotype-associated proteins.

Accumulating evidence shows that the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) can significantly affect the long-term prognosis of coronary artery bypass grafting. This study aimed to explore the factors affecting the proliferation, migration, and phenotypic transformation of VSMCs. First, we stimulated VSMCs with different platelet-derived growth factor-BB (PDGF-BB) concentrations, analyzed the expression of phenotype-associated proteins by Western blotting, and examined cell proliferation by scratch wound healing and the 5-ethynyl-2-deoxyuridine (EdU) assay. VSMC proliferation was induced most by PDGF-BB treatment at 20 ng/mL. miR-200a-3p decreased significantly in A7r5 cells stimulated with PDGF-BB. The overexpression of miR-200a-3p reversed the downregulation of α-SMA (p < 0.001) and the upregulation of vimentin (p < 0.001) caused by PDGF-BB. CCK8 and EdU analyses showed that miR-200a-3p overexpression could inhibit PDGF-BB-induced cell proliferation (p < 0.001). However, flow cytometric analysis showed that it did not significantly increase cell apoptosis. Collectively, the overexpression of miR-200a-3p inhibited the proliferation and migration of VSMCs induced by PDGF-BB, partly by affecting phenotypic transformation-related proteins, providing a new strategy for relieving the restenosis of vein grafts.

Engineering strong man-made cellulosic fibers: a review of the wet spinning process based on cellulose nanofibrils.

With the goal of sustainable development, manufacturing continuous high-performance fibers based on sustainable resources is an emerging research direction. However, compared to traditional synthetic fibers, plant fibers have limited length/diameter and uncontrollable natural defects, while regenerated cellulose fibers such as viscose and Lyocell suffer from inferior mechanical properties. Wet-spun fibers based on nanocelluloses especially cellulose nanofibrils (CNFs) offer superior mechanical performance since CNFs are the fundamental high-performance building blocks of plant cell walls. This review aims to summarize the progress of making CNF wet-spun fibers, emphasizing on the whole wet spinning process including spinning suspension preparation, spinning, coagulation, washing, drying and post-stretching steps. By establishing the relationships between the nano-scale assembling structure and the macroscopic changes in the CNF dope from gels to dried fibers, effective methods and strategies to improve the mechanical properties of the final fibers are analyzed and proposed. Based on this, the opportunities and challenges for potential industrial-scale production are discussed.

A promising Artemisia capillaris Thunb. Leaf proteins with high nutrition, applicable function and excellent antioxidant activity.

The nutritional and functional properties of leaf proteins is a decisive factor for their use in food. This work was aimed to extract defatted Artemisia capillaris Thunb. (ACD) leaf proteins (ACLP), and assess ACLP nutritional quality, functional properties and in vitro antioxidant activity, as well characterize the structure. ACLP had a balanced amino acid profile and high bioavailability (protein digestibility corrected amino acid score (PDCAAS) 99.29 %). Solubility, foaming capacity and emulsifying ability of ACLP correlated positively with pH. Water and oil holding capacity were increased with temperature. Gel electrophoresis shown the protein molecular size was mainly ∼25 kDa, and random coil was the mainly secondary structure while ß-sheet was dominant regular conformation as indicated by circular dichroism (CD). ACLP performed in vitro antioxidant activity which was better after digestion. All data implied ACLP met the WHO/FAO protein quality expectations and had application potential in food.

Hyperglycemia exacerbates cerebral ischemia/reperfusion injury by up-regulating autophagy through p53-Sesn2-AMPK pathway.

Hyperglycemia exacerbates ischemic brain injury by up-regulating autophagy. However, the underlying mechanisms are unknown. This study aims to determine whether hyperglycemia activates autophagy through the p53-Sesn2-AMPK signaling pathway. Rats were subjected to 30-min middle cerebral artery occlusion (MCAO) with reperfusion for 1- and 3-day under normo- and hyperglycemic conditions; and HT22 cells were exposed to oxygen deprivation (OG) or oxygen-glucose deprivation and re-oxygenation (OGD/R) with high glucose. Autophagy inhibitors, 3-MA and ARI, were used both in vivo and in vitro. The results showed that, compared with the normoglycemia group (NG), hyperglycemia (HG) increased infarct volume and apoptosis in penumbra area, worsened neurological deficit, and augmented autophagy. after MCAO followed by 1-day reperfusion. Further, HG promoted the conversion of LC-3I to LC-3II, decreased p62, increased protein levels of aldose reductase, p53, P-p53ser15, Sesn2, AMPK and numbers of autophagosomes and autolysosomes, detected by transmission electron microscopy and mRFP-GFP-LC3 molecular probe, in the cerebral cortex after ischemia and reperfusion injury in animals or in cultured HT22 cells exposed to hypoxia with high glucose content. Finally, experiments with autophagy inhibitors 3-MA and aldose reductase inhibitor (ARI) revealed that while both inhibitors reduced the number of TUNEL positive neurons and reversed the effects of hyperglycemic ischemia on LC3 and p62, only ARI decreased the levels of p53, P-p53ser15. These results suggested that hyperglycemia might induce excessive autophagy to aggravate the brain injury resulted from I/R and that hyperglycemia might activate the p53-Sesn2-AMPK signaling pathway, in addition to the classical PI3K/AKT/mTOR autophagy pathway.

Chitosan alleviates ovarian aging by enhancing macrophage phagocyte-mediated tissue homeostasis.

BACKGROUND: Age-related changes in the ovarian microenvironment are linked to impaired fertility in women. Macrophages play important roles in ovarian tissue homeostasis and immune surveillance. However, the impact of aging on ovarian macrophage function and ovarian homeostasis remains poorly understood. METHODS: Senescence-associated beta-galactosidase staining, immunohistochemistry, and TUNEL staining were used to assess senescence and apoptosis, respectively. Flow cytometry was employed to evaluate mitochondrial membrane potential (MMP) and apoptosis in granulosa cells lines (KGN), and macrophages phagocytosis. After a 2-month treatment with low molecular weight Chitosan (LMWC), ovarian tissues from mice were collected for comprehensive analysis. RESULTS: Compared with the liver and uterus, the ovary displayed accelerated aging in an age-dependent manner, which was accompanied by elevated levels of inflammatory factors and apoptotic cells, and impaired macrophage phagocytic activity. The aged KGN cells exhibited elevated reactive oxygen species (ROS) and apoptotic levels alongside decreased MMP. H2O2-induced aging macrophages showed reduced phagocytosis function. Moreover, there were excessive aging macrophages with impaired phagocytosis in the follicular fluid of patients with diminished ovarian reserve (DOR). Notably, LMWC administration alleviated ovarian aging by enhancing macrophage phagocytosis and promoting tissue homeostasis. CONCLUSIONS: Aging ovarian is characterized by an accumulation of aging and apoptotic granulosa cells, an inflammatory response and macrophage phagocytosis dysfunction. In turn, impaired phagocytosis of macrophage contributes to insufficient clearance of aging and apoptotic granulosa cells and the increased risk of DOR. Additionally, LMWC emerges as a potential therapeutic strategy for age-related ovarian dysfunction.

Meta-Structured Covalent Organic Framework Nanocoatings with Active and Angle-Independent Structural Coloration.

High-performance multifunctional nanocoatings not only protect and enhance substrate materials but also offer additional functionalities. This demands a sophisticated coordination of the coating's inherent properties and microstructural features. Here, a multifunctional active nanocoating via meta-structural engineering of covalent organic framework (COF) deposition materials is presented. This COF nanocoating, characterized by well-defined micropores (1-2 nm), meta-structured textures (30-300 nm), tailored thickness (100-300 nm), and good uniformness, showcases a unique combination of angle-independent structural coloration and ultrafast responsiveness to gaseous stimuli. Remarkably, it demonstrates good compatibility with a wide range of inert substrate materials, from rigid ones like glass and metal to flexible elastomers and nanomaterial films of various shapes and sizes. This versatility enables the facile development of devices that can optically report information about their environments. Examples include chemically active coatings with ultrafast (≈10 ms) color-changing behaviors and programmable actuation behaviors upon exposure to gaseous stimuli, and mechanically active coatings that can detect substrate strain up to 50% yet maintain structural robustness and consistent coloration hue. It is believed that meta-structural engineering of COF nanocoatings on inert substrates can enable them to respond to environmental stimuli, potentially indicating a new trend in developing multifunctional materials and smart devices.

Re-Designing Cellulosic Core-Shell Composite Fibers for Advanced Photothermal and Thermal-Regulating Performance.

Flexible fibers and textiles featuring photothermal conversion and storage capacities are ideal platforms for solar-energy utilization and wearable thermal management. Other than using fossil-fuel-based synthetic fibers, re-designing natural fibers with nanotechnology is a sustainable but challenging option. Herein, advanced core-shell structure fibers based on plant-based nanocelluloses are obtained using a facile co-axial wet-spinning process, which has superior photothermal and thermal-regulating performances. Besides serving as the continuous matrix, nanocelluloses also have two other important roles: dispersing agent when exfoliating molybdenum disulfide (MoS2), and stabilizer for phase change materials (PCM) in the form of Pickering emulsion. Consequently, the shell layer contains well-oriented nanocelluloses and MoS2, and the core layer contains a high content of PCM in a leak-proof encapsulated manner. Such a hierarchical cellulosic supportive structure leads to high mechanical strength (139 MPa), favorable flexibility, and large latent heat (92.0 J g-1), surpassing most previous studies. Furthermore, the corresponding woven cloth demonstrates satisfactory thermal-regulating performance, high solar-thermal conversion and storage efficiency (78.4-84.3%), and excellent long-term performance. In all, this work paves a new way to build advanced structures by assembling nanoparticles and polymers for functional composite fibers in advanced solar-energy-related applications.

Effectiveness of toric soft contact lenses for vision correction in patients with different degrees of astigmatism: a real-world study.

AIM: To assess the visual correction of patients with different degrees of astigmatism with toric soft contact lenses (TSC). METHODS: It was a real-world study with prospective and single-arm design. A total of 384 patients with astigmatism who came for TSC fitting and alignment from November 2022 to January 2023 were included. According to the difference in astigmatism, patients were divided into groups A (cylinder degree: -0.75 to -0.50 D), B (cylinder degree: -1.75 to -1.00 D) and C (cylinder degree ≤ -2.00 D), and followed up on the day of wear, 1wk, 1 and 3mo, mainly to observe visual acuity, refraction, lens fit, visual quality and comfort at 1wk after wear. The visual acuity success rate and the overall success rate of the fitting were evaluation indicators (taking into account the four dimensions of visual acuity, fitting, quality of vision and comfort). The visual acuity success rate was calculated by taking "corrected visual acuity with contact lenses is no less than 1 line or better than best spectacle-corrected visual acuity" (i.e. corrected visual acuity with contact lenses is 1 line below, equal to, one line above or more than best spectacle-corrected visual acuity) as the criterion for visual success, and the the overall success rate of the fitting was calculated by using the comprehensive indicators (visual acuity, fit, visual quality, comfort) to meet certain conditions as the judgment criteria for successful fitting. RESULTS: After 1wk of wearing TSC, the visual acuity success rates of patients were 100% (207/207), 98.58% (139/141) and 97.22% (35/36) in the three groups, respectively, with residual cylinder closed to 0. The acceptability of the lens fitting was over 95%; the incidence of adverse visual symptoms was within 10% and the comfort acceptability was over 97%. The overall success rate of fitting for patients with high, medium and low astigmatism was 93.72% (194/207), 90.78% (128/141) and 88.89% (32/36), respectively. CONCLUSION: TSC (model: G&G POP·CT) are effective in correcting astigmatism in patients with different degrees of astigmatism.

MiR-20b-5p involves in vascular aging induced by hyperhomocysteinemia.

Hyperhomocysteinemia (HHcy) is an independent risk factor of atherosclerosis (AS). Some reports have shown that homocysteine (Hcy) could accelerate the development of AS by promoting endothelial cell senescence. miRNAs were widely involved in the pathophysiology of HHcy. However, few studies have focused on the changes of miRNA-mRNA networks in the artery of HHcy patients. For this reason, RNA-sequencing was adopted to investigate the expression of miRNA and mRNA in HHcy model mouse arteries. We found that the expression of 216 mRNAs and 48 miRNAs were significantly changed. Using TargetScan and miRDB web tools, 29 miRNA-mRNA pairs were predicted. Notably, miR-20b-5p and FJX1 shared the highest predicted score in TargetScan, and further study indicated that the miR-20b-5p inhibitor significantly upregulated the FJX1 expression in HHcy human umbilical vein endothelial cells (HUVECs) model. PPI analysis revealed an important sub-network which was centered on CDK1. Gene ontology (GO) enrichment analysis showed that HHcy had a significant effect on cell cycle. Further experiments found that Hcy management increased reactive oxygen species (ROS) generation, the activity of senescence associated ß-galactosidase (SA-ß-gal) and the protein expression of p16 and p21 in HUVECs, which were rescued by miR-20b-5p inhibitor. In general, our research indicated the important role of miR-20b-5p in HHcy-related endothelial cell senescence.

Effect of vitamin D3 supplementation in winter on physical performance of university students: a one-month randomized controlled trial.

BACKGROUND: There is epidemiological evidence which suggests an association between 25-hydroxyvitamin D [25(OH)D] levels and bone and muscle function; however, it is unclear whether vitamin D supplementation has an added benefit beyond bone health. Here, we investigated the effects of vitamin D3 supplementation (1 month) on physical performance in Chinese university students in winter. METHODS: One hundred and seventeen eligible subjects with 25(OH)D (19.2 ± 7.8 ng/mL) were randomly assigned to either vitamin D3 supplement (N = 56; 1000 IU/day) or the control (N = 61) group for 1 month. Pre- and post-measurements included: 1) serum levels of 25(OH)D; 2) musculoskeletal and pulmonary function [vertical jump height (VJH) and right handgrip strength (RHS), forced vital capacity (FVC), and forced expiratory volume at 1s (FEV1)]; 3) bone turnover markers [parathyroid hormone (PTH), n-terminal osteocalcin (N-MID), and calcium]; 4) hemoglobin-related parameters [hemoglobin (Hb), hematocrit (HCT), red blood cells (RBC), and red cell distribution width (RDW)]; 5) lipid parameters [total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)]; 6) Fatigue-related indicators [serum creatine kinase (CK), lactate dehydrogenase (LDH), and total testosterone (T)]. In addition, aerobic capacity was assessed by measuring maximal oxygen uptake (VO2max) at baseline. RESULTS: During wintertime, supplementation with 1000 IU/d of vitamin D3 significantly increased serum 25(OH)D levels (from 18.85 ± 7.04 to 26.98 ± 5.88 ng/mL, p < 0.05), accompanied by a decrease of PTH (p < 0.05). However, vitamin D3 supplementation did not significantly impact the physical performance, serum lipid parameters, and bone turnover markers of students. Furthermore, 25(OH)D was found to be positively correlated with VJH and negatively correlated with PTH and TC at the beginning and end of the study (p < 0.05). In addition, the multiple linear regression analysis showed that 25(OH)D combined with athletic, gender, height, weight, Hb, and FVC could account for 84.0% of the VO2max value. CONCLUSIONS: The study demonstrated that one-month of 1000 IU/d of vitamin D3 supplementation during the winter had beneficial effects on 25(OH)D status and PTH. However, vitamin D3 intervention was not sufficient to improve physical performance. Furthermore, 25(OH)D levels combined with athletic, Hb and FVC could be a predictor of VO2max.

Involvement in treatment decision-making and self-reported efficacy among patients with advanced colorectal cancer: a nationwide multi-center cross-sectional study.

Introduction: This cross-sectional study evaluated the involvement of patients with advanced colorectal cancer (CRC) in treatment decision-making, assessed the treatment efficacy according to their self-reports, and investigated the influencing factors. Methods: Patients with advanced CRC were recruited from 19 hospitals from March 2020 to March 2021 by a multi-stage multi-level sampling method. A self-designed questionnaire was used to collect demographic and clinical characteristics, involvement of CRC patients in treatment decision-making, treatment methods, and self-reported efficacy. Univariate and unordered multinomial logistic regression analyses were used to evaluate the factors affecting the involvement in treatment decision-making and self-reported efficacy. Results: We enrolled 4533 patients with advanced CRC. The average age at diagnosis was 58.7 ± 11.8 years. For the treatment method, 32.4% of patients received surgery combined with chemotherapy, 13.1% of patients underwent surgery combined with chemotherapy and targeted therapy, and 9.7% of patients were treated with surgery alone. For treatment decision-making, 7.0% of patients were solely responsible for decision-making, 47.0% of patients shared treatment decision-making with family members, 19.0% of patients had family members solely responsible for treatment decision-making, and 27.0% of patients had their physicians solely responsible for treatment decision-making. Gender, age, education level, family income, marital status, treatment cost, hospital type, and treatment method were significantly associated with the involvement of patients in treatment decision-making. A total of 3824 patients submitted self-reported efficacy evaluations during treatment. The percentage of patients with good self-reported efficacy was 76.5% (for patients treated for the first time), 61.7% (for patients treated for the second time), and 43.2% (for patients treated after recurrence and metastasis), respectively. Occupation, education level, average annual family income, place of residence, time since cancer diagnosis, hospital type, clinical stage, targeted therapy, and involvement in treatment decision-making were the main influencing factors of self-reported efficacy of treatment. Discussion: Conclusively, CRC patients are not highly dominant in treatment decision-making and more likely to make treatment decisions with their family and doctors. Timely and effective communication between doctors and patients can bolster patient involvement in treatment decision-making.

Cyclodextrin-based metal-organic framework materials: Classifications, synthesis strategies and applications in variegated delivery systems.

Metal-organic frameworks (MOFs) are coordination compounds that possess an adjustable structure and controllable function. Despite their wide applications in various industries, the use of MOFs in the fields of food and biomedicine is limited mainly due to their potential biological toxicity. Researchers have thus focused on developing biocompatible MOFs to address this issue. Among them, cyclodextrin-based metal-organic frameworks (CD-MOFs) have emerged as a promising alternative. CD-MOFs are novel MOFs synthesized using naturally carbohydrate cyclodextrin and alkali metal cations, and possess renewable, non-toxic, and edible characteristics. Due to their high specific surface area, controllable porosity, great biocompatibility, CD-MOFs have been widely used in various delivery systems, such as encapsulation of nutraceuticals, flavors, and antibacterial agents. Although the field of CD-MOF materials is still in its early stages, they provide a promising direction for the development of MOF materials in the delivery field. This review describes classification and structural characteristics, followed by an introduction to formation mechanism and commonly used synthetic methods for CD-MOFs. Additionally, we discuss the status of the application of various delivery systems based on CD-MOFs. Finally, we address the challenges and prospects of CD-MOF materials, with the aim of providing new insights and ideas for their future development.

Combinatorial Synthesis of Covalent Organic Framework Particles with Hierarchical Pores and Their Catalytic Application.

Precise tailoring of the aggregation state of covalent organic frameworks (COFs) to form a hierarchical porous structure is critical to their performance and applications. Here, we report a one-pot and one-step strategy of using dynamic combinatorial chemistry to construct imine-based hollow COFs containing meso- and macropores. It relies on a direct copolymerization of three or more monomers in the presence of two monofunctional competitors. The resulting particle products possess high crystallinity and hierarchical pores, including micropores around 0.93 nm, mesopores widely distributed in the range of 3.1-32 nm, and macropores at about 500 nm, while the specific surface area could be up to 748 m2·g-1, with non-micropores accounting for 60% of the specific surface area. The particles demonstrate unique advantages in the application as nanocarriers for in situ loading of Pd catalysts at 93.8% loading efficiency in the copolymerization of ethylene and carbon monoxide. The growth and assembly of the copolymer could thus be regulated to form flower-shaped particles, efficiently suppressing the fouling of the reactor. The copolymer's weight-average molecular weight and the melting temperature are also highly improved. Our method provides a facile way of fabricating COFs with hierarchical pores for advanced applications in catalysis.

Real-World Utilization, Barriers, and Factors Associated With the Targeted Treatment of Metastatic Colorectal Cancer Patients in China: A Multi-Center, Hospital-Based Survey Study.

Objectives: To explore the utilization, barriers, and factors associated with the targeted treatment of Chinese metastatic colorectal cancer (mCRC) patients. Methods: A total of 1,688 mCRC patients from 19 hospitals in 14 cities were enrolled from March 2020 to March 2021 using stratified, multistage cluster sampling. The use of targeted therapy and any barriers patients experienced were collected. Logistic regression analyses were conducted to identify the factors associated with initiating targeted treatment. Results: About 51.6% of the patients initiated targeted therapy, of whom 44.5%, 20.2%, and 35.2% started first-, second-, and third-line treatment, respectively. The most reported barriers were high medical costs and a lack of belief in the efficacy of targeted therapy. Patients treated in the general hospital, diagnosed at an older age, less educated, and who had a lower family income, no medical insurance, poor health-related quality of life, metastasis outside the liver/lung or systemic metastasis, a shorter duration of mCRC were less likely to initiate targeted therapy. Conclusion: Reduced medical costs and interventional education to improve public awareness could facilitate the use of targeted treatment for mCRC.

CERS4 predicts positive anti-PD-1 response and promotes immunomodulation through Rhob-mediated suppression of CD8+Tim3+ exhausted T cells in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the main malignant tumors with high mortality and short survival time. Immunotherapy has become the standard treatment for advanced NSCLC, but it has the problems of drug resistance and low response rate. Therefore, obtaining effective biomarkers to predict and enhance immune checkpoint inhibitors (ICIs) efficacy in NSCLC is important. Sphingolipid metabolism is recently found to be closely involved in tumor immunotherapy. CERS4, an important sphingolipid metabolizing enzyme, is positively correlated with the efficacy of anti-PD-1 therapy for NSCLC. Upregulation of CERS4 expression could improve the efficacy of anti-PD-1 therapy for NSCLC. High expression of CERS4 could downregulate the expression of Rhob in tumor. Significantly, the ratio of CD4+/CD8+ T cell increased and the ratio of Tim-3+/CD8+ T cell decreased in spleen and peripheral blood cells. When Rhob was knocked out, the efficacy of PD-1 mAb treatment increased, and the frequency of Tim-3+ CD8+ T cell decreased. This finding further confirmed the role of sphingolipid metabolites in regulating the immunotherapeutic function of NSCLC. These metabolites may improve the efficacy of PD-1 mAb in NSCLC by regulating the CERS4/Rhob/Tim-3 axis. Overall, this study provided a potential and effective target for predicting and improving the efficacy of ICIs for NSCLC. It also provided a new perspective for the study on the mechanisms of ICIs resistance for NSCLC.

Nanocellulose-Based Hollow Fibers for Advanced Water and Moisture Management.

Natural plant fibers such as cotton have favorable performance in water and moisture management; however, they suffer from inferior processing ability due to limited diameter and length, as well as natural defects. Although commercially available regenerated cellulose fibers such as lyocell fibers can have tunable structures, they rely on the complete dissolution of cellulose molecules, including the highly crystalline parts, leading to inferior mechanical properties. Through a specially designed coaxial wet-spinning process, we prepare a type of hollow fiber using only cellulose nanofibrils (CNFs) as building blocks. It mimics cotton fibers with a lumen structure but with a tunable diameter and a long length. Moreover, such hollow fibers have superior mechanical properties with a Young's modulus of 24.7 GPa and tensile strength of 341 MPa, surpassing lyocell fibers and most wet-spun CNF-based fibers. Importantly, they have 10 times higher wicking ability, wetting rate, drying rate, and maximum wetting ratio compared to lyocell fibers. Together with a superior long-term performance after 500 rounds of wetting-drying tests, such CNF-based hollow fibers are sustainable choices for advanced textile applications. And this study provides a greater understanding of nanoscale building blocks and their assembled macromaterials, which may help to reveal the magic hierarchical design of natural materials, in this case, plant fibers.