Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus.

Systemic lupus erythematosus (SLE) is prototypical autoimmune disease driven by pathological T cell-B cell interactions1,2. Expansion of T follicular helper (TFH) and T peripheral helper (TPH) cells, two T cell populations that provide help to B cells, is a prominent feature of SLE3,4. Human TFH and TPH cells characteristically produce high levels of the B cell chemoattractant CXCL13 (refs. 5,6), yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4+ T cell phenotypes in patients with SLE, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4+ T cells. Transcriptomic, epigenetic and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ TPH/TFH cell differentiation and promote an IL-22+ phenotype. Type I interferon, a pathogenic driver of SLE7, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ TPH/TFH cells on a polarization axis opposite from T helper 22 (TH22) cells and reveal AHR, JUN and interferon as key regulators of these divergent T cell states.

Effect of Calcination Atmosphere on the Performance of Cu/Al2O3 Catalyst for the Selective Hydrogenation of Furfural to Furfuryl Alcohol.

The selective hydrogenation of the biomass platform molecule furfural (FAL) to produce furfuryl alcohol (FA) is of great significance to alleviate the energy crisis. Cu-based catalysts are the most commonly used catalysts, and their catalytic performance can be optimized by changing the preparation method. This paper emphasized the effect of calcination atmosphere on the performance of a Cu/Al2O3 catalyst for the selective hydrogenation of FAL. The precursor of the Cu/Al2O3 catalyst prepared by the ammonia evaporation method was treated with different calcination atmospheres (N2 and air). On the basis of the combined results from the characterizations using in situ XRD, TEM, N2O titration, H2-TPR and XPS, the Cu/Al2O3 catalyst calcined in the N2 atmosphere was more favorable for the dispersion and reduction of Cu species and the reduction process could produce more Cu+ and Cu0 species, which facilitated the selective hydrogenation of FAL to FA. The experimental results showed that the N2 calcination atmosphere improved the FAL conversion and FA selectivity, and the FAL conversion was further increased after reduction. Cu/Al2O3-N2-R exhibited the outstanding performance, with a high yield of 99.9% of FA after 2 h at 120 °C and an H2 pressure of 1 MPa. This work provides a simple, efficient and economic method to improve the C=O hydrogenation performance of Cu-based catalysts.

Ribosomal Dysregulation in Metastatic Laryngeal Squamous Cell Carcinoma: Proteomic Insights and CX-5461's Therapeutic Promise.

One of the main barriers to the successful treatment of laryngeal squamous cell carcinoma (LSCC) is postoperative progression, primarily due to tumor cell metastasis. To systematically investigate the molecular characteristics and potential mechanisms underlying the metastasis in laryngeal cancer, we carried out a TMT-based proteomic analysis of both cancerous and adjacent non-cancerous tissues from 10 LSCC patients with lymph node metastasis (LNM) and 10 without. A total of 5545 proteins were quantified across all samples. We identified 57 proteins that were downregulated in LSCC with LNM, which were enriched in cell adhesion pathways, and 69 upregulated proteins predominantly enriched in protein production pathways. Importantly, our data revealed a strong correlation between increased ribosomal activity and the presence of LNM, as 18 ribosomal subunit proteins were found to be upregulated, with RPS10 and RPL24 being the most significantly overexpressed. The potential of ribosomal proteins, including RPS10 and RPL24, as biomarkers for LSCC with LNM was confirmed in external validation samples (six with LNM and six without LNM) using Western blotting and immunohistochemistry. Furthermore, we have confirmed that the RNA polymerase I inhibitor CX-5461, which impedes ribosome biogenesis in LSCC, also decreases the expression of RPS10, RPL24, and RPS26. In vitro experiments have revealed that CX-5461 moderately reduces cell viability, while it significantly inhibits the invasion and migration of LSCC cells. It can enhance the expression of the epithelial marker CDH1 and suppress the expression of the mesenchymal markers CDH2, VIM, and FN at a dose that does not affect cell viability. Our study broadens the scope of the proteomic data on laryngeal cancer and suggests that ribosome targeting could be a supplementary therapeutic strategy for metastatic LSCC.

Construction of Nanofibrillar Networked Wood Aerogels Derived from Typical Softwood and Hardwood: A Comparative Study on the In Situ Formation Mechanism of Nanofibrillar Networks.

The construction of networks within natural wood (NW) lumens to produce porous wood aerogels (WAs) with fascinating characteristics of being lightweight, flexible, and porous is significant for the high value-added utilization of wood. Nonetheless, how wood species affect the structure and properties of WAs has not been comprehensively investigated. Herein, typical softwood of fir and hardwoods of poplar and balsa are employed to fabricate WAs with abundant nanofibrillar networks using the method of lignin removal and nanofibril's in situ regeneration. Benefiting from the avoidance of xylem ray restriction and the exposure of the cellulose framework, hardwood has a stronger tendency to form nanofibrillar networks compared to softwood. Specifically, a larger and more evenly distributed network structure is displayed in the lumens of balsa WAs (WA-3) with a low density (59 kg m-3), a high porosity (96%), and high compressive properties (strain = 40%; maximum stress = 0.42 MPa; height retention = 100%) because of the unique structure and properties of WA-3. Comparatively, the specific surface area (SSA) exhibits 25-, 27-, and 34-fold increments in the cases of fir WAs (WA-1), poplar WAs (WA-2), and WA-3. The formation of nanofibrillar networks depends on the low-density and thin cell walls of hardwood. This work offers a foundation for investigating the formation mechanisms of nanonetworks and for expanding the potential applications of WAs.

Mobile phone problem use and depressive symptoms: the mediating role of social support and attitude to aging among Chinese older adults.

BACKGROUND: Little is known about mobile phone problem use (MPPU) among older adults. This study investigated critical factors affecting MPPU and filled the gap between MPPU and depressive symptoms in older people. METHODS: A cross-sectional study was conducted in community (n = 376) with questionnaires of Multidimensional Scale of Perceived Social Support (MSPSS), Geriatric Depression Scale (GDS-15), Attitudes to Aging Questionnaire (AAQ) and Mobile Phone Problem Use Scale (MPPUS). RESULTS: 80.9% of older people used smartphones and spend less than three hours on mobile phone per day. The average MPPU score of Chinese elderly is greater than the cut off to 41. Female (ß = -0.11, P = 0.037), living with spouse (ß = -0.17, P = 0.03), and late marriage age (ß = -0.16, P = 0.007) are less likely to develop MPPU. The relationship between MPPU and depressive symptoms was partially mediated by social support and attitude to aging. CONCLUSION: Elderly people generally have higher MPPU scores. MPPU was associated with depressive symptoms, through social support and attitude to aging.

A nanobody inhibiting porcine reproductive and respiratory syndrome virus replication via blocking self-interaction of viral nucleocapsid protein.

Porcine reproductive and respiratory syndrome (PRRS) is a serious global pig industry disease. Understanding the mechanism of viral replication and developing efficient antiviral strategies are necessary for combating with PRRS virus (PRRSV) infection. Recently, nanobody is considered to be a promising antiviral drug, especially for respiratory viruses. The present study evaluated two nanobodies against PRRSV nucleocapsid (N) protein (PRRSV-N-Nb1 and -Nb2) for their anti-PRRSV activity in vitro and in vivo. The results showed that intracellularly expressed PRRSV-N-Nb1 significantly inhibited PRRSV-2 replication in MARC-145 cells (approximately 100%). Then, the PRRSV-N-Nb1 fused with porcine IgG Fc (Nb1-pFc) as a delivering tag was produced and used to determine its effect on PRRSV-2 replication in porcine alveolar macrophages (PAMs) and pigs. The inhibition rate of Nb1-pFc against PRRSV-2 in PAMs could reach >90%, and it can also inhibit viral replication in vivo. Epitope mapping showed that the motif Serine 105 (S105) in PRRSV-2 N protein was the key amino acid binding to PRRSV-N-Nb1, which is also pivotal for the self-interaction of N protein via binding to Arginine 97. Moreover, viral particles were not successfully rescued when the S105 motif was mutated to Alanine (S105A). Attachment, entry, genome replication, release, docking model analysis, and blocking enzyme-linked immunosorbent assay (ELISA) indicated that the binding of PRRSV-N-Nb1 to N protein could block its self-binding, which prevents the viral replication of PRRSV. PRRSV-N-Nb1 may be a promising drug to counter PRRSV-2 infection. We also provided some new insights into the molecular basis of PRRSV N protein self-binding and assembly of viral particles.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) causes serious economic losses to the swine industry worldwide, and there are no highly effective strategies for prevention. Nanobodies are considered a promising novel approach for treating diseases because of their ease of production and low costing. Here, we showed that PRRSV-N-Nb1 against PRRSV-N protein significantly inhibited PRRSV-2 replication in vitro and in vivo. Furthermore, we demonstrated that the motif Serine 105 (S105) in PRRSV-N protein was the key amino acid to interact with PRRSV-N-Nb1 and bond to its motif R97, which is important for the self-binding of N protein. The PRRSV-N-Nb1 could block the self-interaction of N protein following viral assembly. These findings not only provide insights into the molecular basis of PRRSV N protein self-binding as a key factor for viral replication for the first time but also highlight a novel target for the development of anti-PRRSV replication drugs.

Hydrodynamics of Butterfly-Mode Flapping Propulsion of Dolphin Pectoral Fins with Elliptical Trajectories.

This article aims to numerically study the hydrodynamic performance of the bionic dolphin equipped with a pair of rigid pectoral fins. We use dynamic-grid technology and user-defined functions to simulate a novel butterfly-mode flapping propulsion of the fins. This pattern of propulsion is composed of three angular degrees of freedom including the pitch angle ϕp, the azimuth angle ϕa and the roll angle ϕr, which can be divided into four stages for analysis within a single cycle. The stroke of one single pectoral fin can be approximated as an ellipse trajectory, where the amplitudes of ϕa and ϕp, respectively, determine the major and minor axes of the ellipse. The fluid dynamics involved in the specific butterfly pattern is mathematically formulated, and numerical simulation is conducted to investigate the propulsion quantitatively. The results show that the dolphin with a higher water striking frequency f can acquire higher propulsion speed and efficiency. Furthermore, the shape of the ellipse trajectory under different conditions could also have different propulsion effects. The periodic generation and disappearance of vortex structures in the butterfly flapping mode show the evolution process of fluid flow around a pair of pectoral fins, which reveals the influence of motion parameters on fluid dynamics under different working conditions.

Exploring associations between social media addiction, social media fatigue, fear of missing out and sleep quality among university students: A cross-section study.

BACKGROUND: Social media use has been linked to poor sleep outcomes among university students in the cyber age, but the association between the negative consequences of social media use and sleep problems is not yet well understood. The present study investigated the relationships among social media usage, social media fatigue (SMF), fear of missing out (FoMO), social media addiction (SMA) and sleep quality in university students. METHOD: An online survey was administered to 2744 respondents that included the Pittsburgh Sleep Quality Index (PSQI); questionnaires evaluating FoMO, SMF, and SMA; and questions regarding sleep duration, social media use, health status, and demographic information. RESULT: A total of 19.9% of respondents suffered from sleep disturbance. A total of 15.6% of participants had sleep durations less than 5 h, and 21.6% of subjects had sleep durations longer than 9 h. Sleep quality was positively associated with SMF (OR = 1.387, 95% CI: 1.103~1.743), and SMA (OR = 1.415, 95% CI: 1.118~1.791). The relationship between FoMO and sleep disturbance was not significant. Compared to a sleep duration > 9 h, SMF increased the risk of shorter sleep durations [5-6 h sleep (OR = 2.226, 95% CI: 1.132~4.375), 6-7 h sleep (OR = 1.458, 95% CI: 1.061~2.002), and 7-8 h sleep (OR = 1.296, 95% CI: 1.007~1.670)]. FoMO and SMA did not significantly affect sleep duration. In addition, SMA (OR = 3.775, 95% CI: 3.141~4.537), FoMO (OR = 3.301, 95% CI: 2.753~3.958), and sleep disorders (OR = 1.284, 95% CI: 1.006~1.638) increased SMF. CONCLUSION: Upon experiencing negative consequences of social media use, such as SMF and SMA, university students were likely to experience sleep problems. Further research exploring the interventions that improve sleep and alleviate negative consequences of social media use should be conducted.

Severe congenital neutropenia and liver abscess: Surgical treatment breaks the vicious cycle.

Here, we present a case with genetically confirmed SCN. The main symptom of the child was recurring fever. The combination of antibiotics combined with G-CSF injection was proved to be insufficient, and the patient developed "solid" liver abscess. After undergoing surgical anatomical hepatic lobectomy, the child's infection symptoms showed improvement. The postoperative culture of the purulent material from the liver infection lesion revealed an infection with Staphylococcus aureus. Our case raises the possibility of pathogen sources and routes of infection, clinical characteristics, and effective treatment for SCN patients with concomitant liver abscess.

In Situ Lignin Adhesion for High-Performance Bamboo Composites.

Bamboo composite is an attractive candidate for structural materials in applications such as construction, the automotive industry, and logistics. However, its development has been hindered due to the use of harmful petroleum-derived synthetic adhesives or low-bonding biobased adhesives. Herein, we report a novel bioadhesion strategy based on in situ lignin bonding that can process natural bamboo into a scalable and high-performance composite. In this process, lignin bonds the cellulose fibrils into a strong network via a superstrong adhesive interface formed by hydrogen bonding and nanoscale entanglement. The resulting in situ glued-bamboo (glubam) composite exhibits a record-high shear strength of ∼4.4 MPa and a tensile strength of ∼300 MPa. This in situ lignin adhesion strategy is facile, highly scalable, and cost-effective, suggesting a promising route for fabricating strong and sustainable structural bamboo composites that sequester carbon and reduce our dependence on petrochemical-based adhesives.

Temperature and strain simultaneous sensing measurement based on an all-fiber Mach-Zehnder interferometer and fiber Bragg grating.

We designed and fabricated what we believe to be a novel dual-parameter fiber optic sensor for simultaneous measurement of temperature and strain, which was composed of a femtosecond laser inscribed fiber Bragg grating (FBG), three segments of a single-mode fiber (SMF), and two segments of a multimode fiber (MMF), forming a SMF-MMF-FBG-MMF-SMF structure. The FBG and Mach-Zehnder interferometer (MZI) were present in this structure so that the changes of the temperature and strain parameters can be sensed by the shifts of the reflection center wavelength of the FBG and the interference valley wavelength of the MZI. We simulated the light field distribution of the sensor structure, compared the shapes of the interference spectra formed by the MZI structure with different sensing arm lengths of 25, 35, and 45 mm, and analyzed the spectra in the spatial frequency domain. The simulation results showed that the interference spectrum of the MZI structure with a 25 mm length sensing arm was clearer and more suitable for the experiment. The experimental results showed that the temperature sensitivity of the FBG and MZI was 14.81 and 43.54 pm/°C in the range of 80°C to 240°C, and the strain sensitivity was 1.49 and -2.58 pm/µÎµ in the range of 0 to 1200 µÎµ, with a high linearity and excellent repeatability. The sensor is economical, sensitive, and convenient to fabricate, and exhibits promising applications in the fields of biochemical medical detection and industrial production monitoring.

Development of a Variable-Configuration Bionic Robotic Fish.

Bionic robotic fish have advantages over traditional underwater propulsion. Most of the existing studies have been conducted with only one type of fish as a bionic object, but a single propulsion mode may not be able to achieve the different needs of underwater operations. In this paper, we designed a pneumatic variable-configuration soft bionic fish and completed the overall structure design. It was built with a cownose ray as the main-configuration bionic object and a Caranx melampygus as the secondary-configuration bionic object. The base structure, actuators, and variable-configuration modules of the robot were made using flexible materials. After completing the design of the structure and control system of the robot, the prototype was manufactured and an underwater test was completed. The tests results indicated that the robot fish could achieve underwater linear propulsion and turning movements in both configurations. The maximum propulsion speed of the main configuration was 38.24 mm/s and the turning angle speed was 5.6°/s, and the maximum propulsion speed of its secondary configuration was 43.05 mm/s and the turning angle speed was 30°/s. The feasibility of the machine fish structure and control scheme were verified.

Pure cellulose nanofiber separator with high ionic conductivity and cycling stability for lithium-ion batteries.

Conventional polyolefin separators are constrained by poor electrolyte wettability, inferior thermal stability, and low ionic conductivity, which seriously restrict their application in high-performance lithium-ion batteries (LIBs). Herein, cellulose nanofiber (CNF) as the matrix and tert-butyl alcohol (TBA) as the dispersion medium were used to prepare the pure CNF separators for LIBs by a facile filtration method. The effects of the drying temperature on the pore structure, electrolyte wettability, mechanical properties, thermal stability, and ionic conductivity of the separators were comprehensively investigated. The results showed that the freeze-dried separator at -80 °C with TBA as the dispersion medium (TBA-FD) had the best overall performance, with the porosity and electrolyte uptake up to 70.8 % and 296 %, respectively, as well as the ionic conductivity up to 1.90 mS/cm. The CNF separators had no apparent thermal shrinkage at 160 °C, illustrating good thermal stability. Moreover, the LiFePO4/lithium metal battery assembled with the TBA-HD (tert-butyl alcohol as the dispersion medium for heat-drying at 80 °C) and TBA-FD separators displayed superior cycling stability (with a capacity retention rate up to 97.5 % and 96.4 %, respectively) and rate performance. The pure CNF separators with good performance prepared by the facile method are greatly promising for high-performance LIBs.

A Comparative and Collaborative Study of the Hydrodynamics of Two Swimming Modes Applicable to Dolphins.

This paper presents a hydrodynamics study that examines the comparison and collaboration of two swimming modes relevant to the universality of dolphins. This study utilizes a three-dimensional virtual swimmer model resembling a dolphin, which comprises a body and/or caudal fin (BCF) module, as well as a medium and/or paired fin (MPF) module, each equipped with predetermined kinematics. The manipulation of the dolphin to simulate various swimming modes is achieved through the application of overlapping grids in conjunction with the parallel hole cutting technique. The findings demonstrate that the swimming velocity and thrust attained through the single BCF mode consistently surpass those achieved through the single MPF mode and collaborative mode. Interestingly, the involvement of the MPF mode does not necessarily contribute to performance enhancement. Nevertheless, it is encouraging to note that adjusting the phase difference between the two modes can partially mitigate the limitations associated with the MPF mode. To further investigate the potential advantages of dual-mode collaboration, we conducted experiments by increasing the MPF frequency while keeping the BCF frequency constant, thus introducing the concept of frequency ratio (ß). In comparison to the single BCF mode, the collaborative mode with a high ß exhibits superior swimming velocity and thrust. Although its efficiency experiences a slight decrease, it tends to stabilize. The corresponding flow structure indirectly verifies the favorable impact of collaboration.

A Prospective and Randomized Control Study on Effects of Thymalfasin for Injection on Perioperative Immune Function and Long-term Prognosis of Patients with Colorectal Cancer.

The objective of this study is to explore the effects of thymalfasin for injection on perioperative immune function and long-term prognosis of patients with colorectal cancer (CRC). In total, 400 patients who entered the groups from February 2019 to January 2021 and underwent radical resection of CRC in the Fourth Hospital of Hebei Medical University were the study subjects. They were separated into experimental group (0-199, XELOX chemotherapy and thymalfasin for injection) and control group (200-400, XELOX chemotherapy) by random number table, and the experimental group was randomly divided into conventional-dose group (n = 100, 1.6 mg of thymalfasin for injection, twice a week) and high-dose group (n = 100, 1.6 mg of thymalfasin for injection, thrice a week) according to a ratio of 1:1, to analyze the effects of different treatment schemes on perioperative immune function and long-term prognosis of CRC patients. Compared with control group, the conventional-dose group and high-dose group had notably lower incidences of perioperative infection (P < 0.05), with no significant difference in both groups (P > 0.05). The experimental group had significantly lower overall incidence of early and late postoperative complications, local recurrence rate and the incidence of distant metastasis, and higher perioperative immune function indexes and median disease free survival (DFS) (P < 0.05). The conventional-dose and high-dose thymalfasin for injection effectively improves the perioperative immune function of CRC patients and reduces the incidence of postoperative complications, as an effective treatment for such patients, which can benefit patients.

Biosafety risk assessment of gold and aluminum nanoparticles in tumor-bearing mice.

To improve the biosafety of the nanodelivery system, this study developed novel monodisperse spherical aluminum nanoparticles (Al NPs) and evaluated their cytotoxicity in vitro and distribution and biotoxicity in vivo. Compared with gold nanoparticles of the same size, Al NPs not only had low cytotoxicity in vitro but also did not cause accumulation in major organs in vivo after intravenous injections. No significant abnormalities were observed in the serum biochemical indices of mice injected with Al NPs. Additionally, no substantial changes occurred in the histopathology of major organs, and no apparent biological toxicity was measured after consecutive injections of Al NPs. These results indicate that Al NPs have a good biological safety and provide a new method for developing low-toxicity nanomedicine.

A novel method to generate and transmit 40-tupling frequency millimeter wave over fiber based on remodulation of MZMs.

An novel method to generate 40-tupling frequency millimeter (MMW) based on the remodulation of MZMs and a novel radio over fiber (ROF) system to transmit the generated MMW are proposed. At the central station (CS), the ±4th order sidebands generated by two Mach-Zehnder modulators (MZMs) in parallel are used as the optical carriers for the remodulation. The radio frequency (RF) signal for the remodulation can be generated by injecting the ±4th order sidebands in the photodetector (PD). The main components in the signal after remodulation are ±4th, ±12th and ±20th order sidebands, among them, the +20th sideband is filtered out by a fiber Bragg grating (FBG). After the +20th order sideband is modulated with the downlink data, the ±20th order sidebands are combined again and transmitted to the base station (BS) by optical fiber. At the BS, a part of -20th order sideband is filtered out with a FBG, and with which the uplink data is modulated on it and sent back to the CS for carrier wave reuse. The 40-tupling frequency MMW signal with downlink data is generated by beating the output signal from FBG in the PD. In the case of data rate is 2.5G/bps and the bit error rate is less than 10-9, the transmission distance can exceed 90 km, the power penalty of the uplink and downlink is less than 1 dB and 0.29 dB, respectively. Our scheme has simple structure, high frequency multiplier factor, it has important application prospects in MMW technology.

SHP-2-induced M2 polarization of tumor associated macrophages via IL-4 regulate colorectal cancer progression.

Objective: To explore the effect and molecular mechanism of Src homology region 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) in tumor-associated macrophages (TAMs) repressing the migration and invasion of colorectal cancer (CRC) cells. Methods: The relevant data sets of human colon specimens were obtained from GEO database, and then the performed correlation analysis, principal component analysis and differentially expressed gene (DEGs) analysis on the samples were conducted. GO and KEGG enrichment analysis were performed on the common DEGs, and then functional interaction prediction was performed to verify the gene regulatory circuit of SHP-2. Furthermore, western blot was used to detect the effect of low expression of SHP-2 on related proteins, including the markers of promoting M2 polarization and exosome secretion, and keys proteins of the PI3K pathway. The relationship between SHP-2 and PI3K pathway was further verified by adding PI3K inhibitor LY294002. Finally, the effect of SHP-2 on the function of colon cancer cells was confirmed by wound healing assay and Transwell assay. Results: Through bioinformatics analysis, SHP-2 was screened as a possible key gene affecting CRC. The low expression of SHP-2 promoted the protein levels of Arginase-1 and IL-10 in IL-4 induced M2 macrophages, while inhibited the protein levels of IL-1ß and TNF-α. Meanwhile, low expression of SHP-2 was found to similarly promote the expression of p-PI3K, p-AKT, and the release of exosomes. Interestingly, the promotion was suppressed after the addition of the PI3K inhibitor LY294002. In terms of cellular behavior, wound healing and transwell data showed that low expression of SHP-2 enhanced the migration and invasion abilities of CRC cells. Conclusion: The low expression of SHP-2 induced by PHPS1 may regulate M2 polarization of TAMs and release of exosomes through PI3K/AKT pathway, thereby enhancing the migration and invasion ability of CRC cells.

Heterogeneity of PD-L1 expression and CD8 lymphocyte infiltration in metastatic colorectal cancer and their prognostic significance.

Purpose: In recent years, immune checkpoint inhibitors have become a major therapeutic method for the treatment of metastatic colorectal cancer (mCRC). Growing evidence indicates that tumour-infiltrating lymphocytes (TILs) in the tumour microenvironment are a prerequisite for the effectiveness of PD-1/PD-L1 blockade therapy. In this study, we aimed to compare PD-L1 expression and cluster of differentiation 4 (CD4) and CD8 TIL infiltration in primary tumours and paired metastases. Patients and methods: Altogether, 111 patients with mCRC who underwent surgery at our hospital were included. PD-L1, CD4, and CD8 expression were detected by immunohistochemistry in a tissue microarray. PD-L1 expression was assessed using the combined positivity score (CPS), and a score ≥1 was judged as positive. The area proportion of TILs with positive staining ≥10% was classified as "high", while <10% was classified as "low". Results: We observed the discordance of PD-L1 expression between primary tumours and paired metastases in 35/111 (31.5%) patients (κ = 0.137, P = 0.142). This heterogeneity was significantly correlated with discordance of CD8 TIL infiltration between primary tumours and paired metastases (P = 0.003). Compared with corresponding colorectal cancer tumours, lung metastases showed more CD8 TIL infiltration (P = 0.022, median: 8.5% vs. 5.0%), whereas liver metastases exhibited less CD8 TIL infiltration (P = 0.028, median: 3.0% vs. 5.0%). Area proportion of CD4+ and CD8+ TIL infiltration in lung metastases were all higher than those in liver metastases (P = 0.005, median: 15.0% vs. 9.0%; P = 0.001, median: 8.5% vs. 3.0%). Compared with p MMR (MSI-L/MS-S) subgroup, area proportion of CD8 TIL infiltration in primary tumours and CD4, CD8 TIL infiltration in paired metastases were all higher in d MMR (MSI-H) group (P = 0.026, median: 15.0% vs 5.0%; P = 0.039, median: 15.0% vs 9.0%; P = 0.015, median: 15.0% vs 5.0%). Preoperative chemo/radiotherapy may increase CD8 TIL infiltration in primary tumours (P = 0.045, median: 10.0% vs. 5.0%). CD8 TIL infiltration in primary tumours was an independent predictive factor for overall survival (HR 0.28, 95% CI 0.09-0.93, P = 0.038). Conclusion: Heterogeneity in PD-L1 expression and CD8 TIL infiltration was found between primary tumours and paired metastases in mCRC. CD8 TIL infiltration in primary tumours could independently forecast the overall survival of patients with mCRC.

A facile strategy to fabricate antibacterial hydrophobic, high-barrier, cellulose papersheets for food packaging.

As a traditionally used packaging material, natural cellulose-based paper has poor barrier properties to water and oxygen, which severely limits its wide application in food packaging. In this study, we report a new sustainable approach to producing hydrophobic, high-barrier, and antibacterial packaging materials from cellulose paper. In this process, commercially available microcrystalline cellulose was first modified by long-chain stearic acid to form hydrophobic microcrystalline cellulose ester and then mixed with stearic acid as filler in the subsequent surface coating of bagasse fibre paper. The microcrystalline cellulose ester/stearic acid-coated paper (MSP) exhibited good water repellency and oxygen barrier activity due to a continuous hydrophobic film that formed, which completely covered the pores of the original bagasse fibre paper. The coated MSP sample also showed excellent dimensional stability in water and a good wet tensile strength of 16 MPa. In addition, poly(hexamethylene guanidine) (PHMG) was chemically grafted onto the free carboxyl groups of the MSP surface layer, and the resulting MSP-g-PHMG samples exhibited excellent antibacterial activity against Escherichia coli and Listeria monocytogenes. The biodegradable cellulose-based MSP-g-PHMG sample significantly delayed the decay of raspberry during storage, indicating its potential application in food packaging.