Revolutionizing cancer treatment: enhancing CAR-T cell therapy with CRISPR/Cas9 gene editing technology.

CAR-T cell therapy, a novel immunotherapy, has made significant breakthroughs in clinical practice, particularly in treating B-cell-associated leukemia and lymphoma. However, it still faces challenges such as poor persistence, limited proliferation capacity, high manufacturing costs, and suboptimal efficacy. CRISPR/Cas system, an efficient and simple method for precise gene editing, offers new possibilities for optimizing CAR-T cells. It can increase the function of CAR-T cells and reduce manufacturing costs. The combination of CRISPR/Cas9 technology and CAR-T cell therapy may promote the development of this therapy and provide more effective and personalized treatment for cancer patients. Meanwhile, the safety issues surrounding the application of this technology in CAR-T cells require further research and evaluation. Future research should focus on improving the accuracy and safety of CRISPR/Cas9 technology to facilitate the better development and application of CAR-T cell therapy. This review focuses on the application of CRISPR/Cas9 technology in CAR-T cell therapy, including eliminating the inhibitory effect of immune checkpoints, enhancing the ability of CAR-T cells to resist exhaustion, assisting in the construction of universal CAR-T cells, reducing the manufacturing costs of CAR-T cells, and the security problems faced. The objective is to show the revolutionary role of CRISPR/Cas9 technology in CAR-T cell therapy for researchers.

Clinical Value of Mean Platelet Volume to Platelet Ratio (MPR) in Distinguishing Mass-Forming Chronic Pancreatitis and Pancreatic Cancer.

BACKGROUND: Correctly distinguishing mass-forming chronic pancreatitis (MFCP) from pancreatic cancer (PC) is of clinical significance to determine optimal therapy and improve the prognosis of patients. According to research, inflammation status in PC is different from that in MFCP. Mean platelet volume/platelet ratio (MPR) is a platelet-related inflammation index which has been proven to be valuable in the diagnosis and prognosis of various malignant cancers due to the change in mean platelet volume and platelet count under abnormal inflammatory conditions caused by tumors. Thus, we conducted this study to investigate the clinical value of MPR in distinguishing MFCP from PC. METHODS: We retrospectively analyzed the data of 422 patients who were suspected to have PC during imaging examination at our department from January 2012 to December 2021. Included patients were divided into the PC (n = 383) and MFCP groups (n = 39), according to their pathological diagnosis. Clinical data including MPR were compared within these two groups and the diagnostic value was explored using logistic regression. The ROC curve between MPR and PC occurrence was drawn and an optimal cut-off value was obtained. Propensity score matching was applied to match MFCP patients with PC patients according to their age and carbohydrate antigen 19-9 (CA19-9). Differences in MPR between groups were compared to verify our findings. RESULTS: The area under the ROC curve between MPR and PC occurrence was 0.728 (95%CI: 0.652-0.805) and the optimal cut-off value was 0.045 with a 69.2% sensitivity and 68.0% accuracy. For all the included patients, MPRs in the MFCP and PC groups were 0.04 (0.04, 0.06) and 0.06 (0.04, 0.07), respectively (p = 0.005). In patients with matching propensity scores, MPRs in the MFCP and PC groups were 0.04 (0.03, 0.06) and 0.06 (0.05, 0.08), respectively (p = 0.005). Multiple logistic regression in all included patients and matched patients confirmed MPR and CA19-9 as independent risk markers in distinguishing PC. Combining CA19-9 with MPR can increase the sensitivity and accuracy in diagnosing PC to 93.2% and 89.5%, respectively. CONCLUSION: MPR in PC patients is significantly higher than that in MFCP patients and may be adopted as a potential indicator to distinguish MFCP and PC. Its differential diagnosis capacity can be improved if combined with CA19-9.

Extraction of the Microstructure of Wool Fabrics Based on Structure Tensor.

The trends of "fashionalization", "personalization" and "customization" of wool fabrics have prompted the textile industry to change the original processing design based on the experience of engineers and trial production. In order to adapt to the promotion of intelligent production, the microstructure of wool fabrics is introduced into the finishing process. This article presents an automated method to extract the microstructure from the micro-CT data of woven wool fabrics. Firstly, image processing was performed on the 3D micro-CT images of the fabric. The raw grayscale data were converted into eigenvectors of the structure tensor to segment the individual yarns. These data were then used to calculate the three parameters of diameter, spacing and the path of the center points of the yarn for the microstructure. The experimental results showed that the proposed method was quite accurate and robust on woven single-ply tweed fabrics.

Closed-Loop Recycling of Vinylogous Urethane Vitrimers.

Devising energy-efficient strategies for the depolymerization of plastics and the recovery of their structural components in high yield and purity is key to a circular plastics economy. Here, we report a case study in which we demonstrate that vinylogous urethane (VU) vitrimers synthesized from bis-polyethylene glycol acetoacetates (aPEG) and tris(2-aminoethyl)amine can be degraded by water at moderate temperature with almost quantitative recovery (≈98 %) of aPEG. The rate of depolymerization can be controlled by the temperature, amount of water, molecular weight of aPEG, and composition of the starting material. These last two parameters also allow one to tailor the mechanical properties of the final materials, and this was used to access soft, tough, and brittle vitrimers, respectively. The straightforward preparation and depolymerization of the aPEG-based VU vitrimers are interesting elements for the design of polymer materials with enhanced closed-loop recycling characteristics.

Prognostic value of perioperative serum low-density lipoprotein cholesterol level for postoperative prognosis of pancreatic cancer: a retrospective study.

BACKGROUND: As a common malignant tumour, pancreatic cancer (PC) has the worst clinical outcome. Early evaluation of the postoperative prognosis has certain clinical value. Low-density lipoprotein cholesterol (LDL-c), which is mainly composed of cholesteryl esters, phospholipids, and proteins, plays an important role in transporting cholesterol into peripheral tissues. LDL-c has also been reported to be correlated with the occurrence and progression of malignant tumours and can predict postoperative prognosis in various tumours. AIMS: To determine correlation between serum LDL-c level and clinical outcome in PC patients after surgery. METHODS: Data of PC patients that received surgery at our department from January 2015 to December 2021 were retrospectively analysed. Receiver operating characteristic (ROC) curves between perioperative serum LDL-c at different timepoints and survival rate at postoperative 1-year were drawn, and the optimal cut-off value was calculated. Patients were categorized into low and high LDL-c groups, and their clinical data and outcome were compared. Univariate and multivariate analyses were applied to screen out risk markers for poor prognosis of PC patients after surgery. RESULTS: The area under the ROC curve of serum LDL-c at 4 weeks after surgery and prognosis was 0.669 (95% CI: 0.581-0.757), and the optimal cut-off value was 1.515 mmol/L. The median disease-free survival (DFS) rates of low and high LDL-c groups were 9 months and 16 months, respectively, and the 1-, 2- and 3-year DFS rates were 42.6%, 21.1% and 11.7% in low LDL-c group, respectively, and, 60.2%, 35.3% and 26.2% in high LDL-c group, respectively (P = 0.005). The median overall survival (OS) rates of low and high LDL-c groups were 12 months and 22 months, respectively, and the 1-, 2- and 3-year OS rates were 46.8%, 22.6% and 15.8% in low LDL-c group, respectively, and 77.9%, 46.8% and 30.4% in high LDL-c group, respectively (P = 0.004). Multivariate analysis confirmed low postoperative 4-week serum LDL-c as independent risk marker for early tumour recrudesce and poor clinical outcome in PC patients. CONCLUSION: High postoperative 4-week serum LDL-c is a prognostic marker for prolonged DFS and OS time in PC patients.

Prognostic Value for Perioperative Serum Total Cholesterol Level on Postoperative Long-Term Prognosis of Pancreatic Cancer: A Retrospective Clinical Study.

Cholesterol correlates with occurrence and progression of pancreatic cancer and has predictive value for postoperative prognosis in various cancers. Our study intended to reveal the relationship between perioperative serum total cholesterol (TC) level and postoperative prognosis of pancreatic cancer. We retrospectively analyzed the data of pancreatic cancer patients who underwent surgical treatment at our hospital from January 2015 to December 2021. ROC curves between serum TC level at each time point and 1-year survival rate were drawn, from which study object and optimal cutoff value was determined. Patients were divided into low and high-TC groups, and perioperative data and prognosis were compared. Risk factors for poor postoperative prognosis were identified by univariate and multivariate analysis. Overall survival rates at postoperative 1, 2 and 3 years in the low and high-TC groups were 52.9%, 29.4%, and 15.6% and 80.4%, 47.2%, and 33.8% (p = 0.005), respectively. Multivariate analysis confirmed tumor differentiation degree (RR = 2.054, 95% CI: 1.396-3.025), pTNM stage (RR = 1.595, 95% CI: 1.020-2.494), lymph node metastasis (RR = 1.693, 95% CI: 1.127-2.544), and postoperative 4-week serum TC level (RR = 0.663, 95% CI: 0.466-0.944) as independent risk factors for prognosis of pancreatic cancer. We conclude that postoperative 4-week serum TC level has certain predictive value for long-term postoperative prognosis of pancreatic cancer.

Chemical Upcycling of Conventional Polyureas into Dynamic Covalent Poly(aminoketoenamide)s.

The chemical upcycling of polymers is an emerging strategy to transform post-consumer waste into higher-value chemicals and materials. However, on account of the high stability of the chemical bonds that constitute their main chains, the chemical modification of many polymers proves to be difficult. Here, we report a versatile approach for the upcycling of linear and cross-linked polyureas, which are widely used because of their high chemical stability. The treatment of these polymers or their composites with acetylacetone affords di-vinylogous amide-terminated compounds in good yield. These products can be reacted with aromatic isocyanates, and the resulting aminoketoenamide bonds are highly dynamic at elevated temperatures. We show here that this conversion scheme can be exploited for the preparation of dynamic covalent poly(aminoketoenamide) networks, which are healable and reprocessable through thermal treatment without any catalyst.

Rapid Stress Relaxation, Multistimuli-Responsive Elastomer Based on Dual-Dynamic Covalent Bonds and Aniline Trimer.

Covalent adaptable networks (CANs) are an emerging kind of smart materials in which cross-links are reversible upon some stimuli and then provide malleability and a stimuli-responsive ability to the materials. There is a trend to endow CANs with multistimuli-responsive capabilities and rapid stress relaxation to pursue more advanced applications. To integrate these two features into one material, here, dual-dynamic covalent bonds (imines and boronic esters) and aniline trimer (ACAT) were incorporated into the styrene butadiene elastomer as dynamic cross-links. The obtained CANs were demonstrated with rapid stress relaxation and a relatively low activation energy of 36 ± 1 kJ mol-1, resulting from the synergistic effect of dual-dynamic covalent bonds to rearrange the network at a faster rate than for either imines or boronic esters. Because of the dynamic nature of imines or boronic esters, the elastomer can be recycled upon heat. Moreover, the appearance and configuration of the elastomer could also be manipulated by pH and light because of the inclusion of ACAT. All in all, the coupled multistimuli-responsive behavior and rapid stress relaxation in one single elastomer would potentially be applicable for sensors and actuators with good recyclability.

Integrating Boronic Esters and Anthracene into Covalent Adaptable Networks toward Stimuli-Responsive Elastomers.

Stimuli-responsive polymer materials have a promising potential application in many areas. However, integrating multi-stimuli into one elastomer is still a challenge. Here, we utilized boronic esters and anthracene to prepare a cross-linked poly(styrene-butadiene-styrene) (SBS) which was endowed with responsiveness to three stimuli (light, heat, and alcohols). SBS was first functionalized with a certain amount of dihydroxyl groups via a thiol-ene "click" reaction between unsaturated double bonds in PB block and thioglycerol. Then, 9-anthraceneboronic acid was applied to form a cross-linked SBS network upon heat and ultraviolet radiation (λ = 365 nm). The prepared elastomer was demonstrated to be stimuli-responsive based on the dynamic nature of boronic esters and the reversible dimerization of anthracene. In addition, the mechanical properties of the elastomer could be regulated continuously owing to the stimulus responsiveness to ultraviolet or heat.

Aminoesterenamide Achieved by Three-Component Reaction Heading toward Tailoring Covalent Adaptable Network with Great Freedom.

Covalent adaptable networks (CANs) have recently received extensive interests due to their reprocessability and repairability. Rethinking the libraries of the published CANs, most of them are fabricated by one/two-component reactions and few cases utilize multi-component reactions to construct CANs while multi-component reactions are conductive to tailoring the properties of polymers due to their structural designability and flexible choice of raw materials. A novel kind of dynamic covalent bond named aminoesterenamide is presented through three-component reaction between acetoacetyl, amine and isocyanate. Aminoesterenamide exhibits thermal reversibility through dissociating into vinylogous urethane and isocyanate. When it is used to prepare CANs, the synthesized polymer networks can be reprocessed many times via the exchange reaction between aminoesterenamides. Moreover, the forming of aminoesterenamide involving three starting components imparts CANs with great freedom to tailor their properties. Therefore, the authors believe this method that utilizes three-component reaction to fabricate CANs would bring new stories and perspectives to the exploration of new types of CANs.

MiR-129-5p Restrains Apatinib Resistance in Human Gastric Cancer Cells Via Downregulating HOXC10.

Background: Repeated administration of apatinib has resulted in serious drug resistance in gastric cancer (GC). Previous studies showed that miR-129-5p had a low expression in GC, and homeobox gene C10 (HOXC10), a carcinogenic gene, was highly expressed in GC, while the molecular mechanism of miR-129-5p involved in apatinib resistance in GC cells is still unclear. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-129-5p and HOXC10 in GC tissues or cell lines. The expression levels of associated proteins were detected by Western blot. Cell counting kit-8 (CCK-8), the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and flow cytometry assays were conducted to detect cell viability, proliferation, and apoptosis of MGC-803/AP and AGS/AP cells in vitro. The dual-luciferase reporter assay was used to verify the targeted relationship between miR-129-5p and HOXC10. The xenograft model was established to examine the effect of miR-129-5p in vivo, and the HOXC10 protein expression in tumor xenograft was assessed by immunohistochemistry. Results: MiR-129-5p had a low expression in GC tissues and apatinib-resistant cell lines, while HOXC10 was highly expressed. Meanwhile, overexpression of miR-129-5p and knockdown of HOXC10 could enhance the chemosensitivity of MGC-803/AP and AGS/AP cells. Dual-luciferase reporter assay confirmed miR-129-5p targeted HOXC10 and downregulated its expression level. MiR-129-5p inhibited proliferation and promoted apoptosis of MGC-803/AP and AGS/AP cells by downregulating HOXC10. The experiment in vivo also confirmed that miR-129-5p reduced apatinib resistance in GC cells by targetedly inhibiting HOXC10. HOXC10 was upregulated in GC tumor xenograft tissues. Conclusion: miR-129-5p restrains apatinib-resistant of GC cells by regulating HOXC10.

A high-resolution Asia-Pacific regional coupled prediction system with dynamically downscaling coupled data assimilation.

A regional coupled prediction system for the Asia-Pacific (AP-RCP) (38°E-180°, 20°S-60°N) area has been established. The AP-RCP system consists of WRF-ROMS (Weather Research and Forecast, and Regional Ocean Model System) coupled models combined with local observational information through dynamically downscaling coupled data assimilation (CDA). The system generates 18-day forecasts for the atmosphere and ocean environment on a daily quasi-operational schedule at Pilot National Laboratory for Marine Science and Technology (Qingdao) (QNLM), consisting of 2 different-resolution coupled models: 27 km WRF coupled with 9 km ROMS, 9 km WRF coupled with 3 km ROMS, while a version of 3 km WRF coupled with 3 km ROMS is in a test mode. This study is a first step to evaluate the impact of high-resolution coupled model with dynamically downscaling CDA on the extended-range predictions, focusing on forecasts of typhoon onset, improved precipitation and typhoon intensity forecasts as well as simulation of the Kuroshio current variability associated with mesoscale oceanic activities. The results show that for realizing the extended-range predictability of atmospheric and oceanic environment characterized by statistics of mesoscale activities, a fine resolution coupled model resolving local mesoscale phenomena with balanced and coherent coupled initialization is a necessary first step. The next challenges include improving the planetary boundary physics and the representation of air-sea and air-land interactions to enable the model to resolve kilometer or sub-kilometer processes.

Severity and incidence of complications assessed by the Clavien-Dindo classification following robotic and laparoscopic gastrectomy for advanced gastric cancer: a retrospective and propensity score-matched study.

BACKGROUND: Robot-assisted gastrectomy (RAG) has been increasingly used for the treatment of advanced gastric cancer (AGC), and many advantages over laparoscopy-assisted gastrectomy (LAG) have been reported. However, its postgastrectomy complications still under investigation and the results remain controversial. This study aimed to objectively assess the incidence and severity of complications following RAG vs. LAG using Clavien-Dindo (C-D) classification and to identify risk factors related to complications. METHODS: Five hundred and twenty-seven patients with AGC who underwent RAG or LAG between January 2016 and May 2018 were enrolled in this study. Complications were categorized according to the C-D classification. The complications following RAG and LAG were compared using one-to-one propensity score matching (PSM) analysis and subgroup analyses. Logistic regression analyses were performed to identify risk factors related to complications. RESULTS: RAG was performed in 251 patients (47.6%) and LAG in 276 patients (52.4%). Before PSM, the RAG group had a smaller tumour size (P = 0.004) and less patients with previous abdominal operation (P = 0.013). After PSM, a well-balanced cohort of 446 patients (223 in each group) was further analyzed. Of interest, the incidence of overall and severe complications (C-D grade ≥ IIIa) following the RAG group were significantly fewer than the LAG group (overall, 24.5% vs. 18.8%, P < 0.001; severe, 8.9% vs. 17.5%, P = 0.002). Subgroup analyses showed statistically significant difference were also observed in most stratified parameters. Multivariable analysis identified age ≥ 65 years, total gastrectomy, stage T3-T4a, stage II-III, and operation time ≥ 250 min as independent predictors of overall complications. Additionally, age ≥ 65 years, stage II-III, and operation time ≥ 250 min were confirmed as independent risk factors for severe complications. CONCLUSIONS: RAG with D2 lymphadenectomy is feasible and safe for the treatment of AGC in terms of the lower incidence and severity of complications.