Bacterial indole-3-lactic acid affects epithelium-macrophage crosstalk to regulate intestinal homeostasis.

Tryptophan and its derivatives perform a variety of biological functions; however, the role and specific mechanism of many tryptophan derivatives in intestinal inflammation remain largely unclear. Here, we identified that an Escherichia coli strain (Ec-TMU) isolated from the feces of tinidazole-treated individuals, and indole-3-lactic acid (ILA) in its supernatant, decreased the susceptibility of mice to dextran sulfate sodium-induced colitis. Ec-TMU and ILA contribute to the relief of colitis by inhibiting the production of epithelial CCL2/7, thereby reducing the accumulation of inflammatory macrophages in vitro and in vivo. Mechanistically, ILA downregulates glycolysis, NF-κB, and HIF signaling pathways via the aryl hydrocarbon receptor, resulting in decreased CCL2/7 production in epithelial cells. Clinical evidence suggests that the fecal ILA level is negatively correlated with the progression indicator of inflammatory bowel diseases. These results demonstrate that ILA has the potential to regulate intestinal homeostasis by modulating epithelium-macrophage interactions.

Injectable platelet-rich fibrin promotes proliferation and trichogenic inductivity of dermal papilla cells through activating TGF-ß/Smad signaling pathway.

Dermal papilla cell (DPC) belongs to a specialized mesenchymal stem cell for hair follicle regeneration. Maintaining the ability of DPCs to stimulate hair in vitro culture is important for hair follicle morphogenesis and regeneration. As the third generation of platelet concentrate, injectable platelet-rich fibrin (i-PRF) is a novel biomaterial containing many growth factors and showing promising effects on tissue reconstruction. We aimed to explore the influences of i-PRF on the proliferative, migratory, as well as trichogenic ability of DPCs and compared the effects of i-PRF and platelet-rich plasma (PRP), the first generation of platelet concentrate. Both PRP and i-PRF facilitated DPCs proliferation, and migration, along with trichogenic inductivity as well as stimulated the TGF-ß/Smad pathway, while the impacts of i-PRF were more significant than PRP. A small molecule inhibitor of TGF-beta receptor I, Galunisertib, was also applied to treat DPCs, and it rescued the impacts of i-PRF on the proliferative, migratory, trichogenic inductivity, and proteins-associated with TGF-ß/Smad pathway in DPCs. These findings revealed that i-PRF had better effects than PRP in enhancing the proliferative, migratory, and hair-inducing abilities of DPCs by the TGF-ß/Smad pathway, which indicated the beneficial role of i-PRF in hair follicle regeneration.

A case report of primary central nervous system lymphoma with immune deficiency/disorder setting diagnosed by cerebrospinal fluid cytology.

Cerebrospinal fluid (CSF) cytology of primary central nervous system lymphoma arising in the immune deficiency/dysregulation setting (IDD-PCNSL) has not been described. This study presented a case of IDD-PCNSL-DLBCL, a GCB phenotype who was successfully diagnosed by CSF cytology in conjunction with ICC, ISH, FCM and clinical information.

Spatiotemporal evolution and influencing factors of the allocation of social care resources for the older adults in China.

BACKGROUND: The reasonable allocation of social care resources for the older adults is a key measure to actively respond to population aging. This study aims to evaluate the evolutionary trend, spatial differences and influencing factors of the social elderly care resources (SECR) allocation in China. METHODS: This study constructed a comprehensive index system consisting of three dimensions: material resources, human resources and financial resources, to measure the level of SECR in mainland China. The Kernel density estimation was used to reveal the dynamic evolution trend, and Dagum Gini Coefficient and its decomposition method were used to investigate the equity of SECR allocation. Spatial panel regression models were used to analyze the influencing factors of the allocation of SECR. RESULTS: The level of SECR is rising from 0.197 in 2013 to 0.208 in 2019. The middle-high- and high-level areas of SECR were mainly distributed in the eastern and western China. The Gini coefficient of SECR decreased from 0.262 in 2013 to 0.249 in 2019. Per capita GDP, the proportion of social welfare expenditure in GDP and the proportion of the tertiary industry in GDP have significant positive effects on the allocation of SECR. Population aging and the development of service industry exhibit significant negative spatial spillover effects on the allocation of SECR. CONCLUSIONS: The fairness of the allocation of SECR in China has been improved, while the spatial distribution is imbalanced. Economic development, fiscal input and the development of service industry have significant positive effects while population aging has significant negative effects on the SECR allocation.

Spatial differentiation and driving factors of the high-quality development of undertakings for the aged of China.

BACKGROUND: Promoting the high-quality development (HQD) of undertakings for the aged is an important action to proactively respond to the rapid population aging in China. This study analyzes spatial differentiation and driving factors of the HQD of China's undertakings for the aged. METHODS: Based on a quantitative indicator system consisting of old-age social security, elder care services, health care service and older adults' social participation, the HQD levels of 31 Chinese provincial administrative regions during 2013-2019 are measured by using the entropy weight method. Spatial panel regression models are used to analyze the impact of population aging, economic development and digital technology on the HQD of undertakings for the aged. RESULTS: The comprehensive level of the HQD slightly increased from 0.212 to 2013 to 0.220 in 2019, and the overall level was low. The HQD of the eastern region was the highest (0.292), followed by the western region (0.215), and the central region was the lowest (0.151). The high-high cluster type was mainly distributed in the eastern region; the low-low cluster type was mainly distributed in the western and central regions. Economic development and digital technology have significant positive effects while population aging has significant negative effects on the HQD of undertakings for the aged. CONCLUSION: There is a significantly spatial differentiation in the HQD of China's undertakings for the aged. In order to promote the HQD of undertakings for the aged, it is necessary to identify development gaps through making HQD evaluation and to focus on the indicators that are critical in maintaining sustainable economic development and to develop digital technology in order to get rid of those gaps.

Novel tumour-infiltrating lymphocyte-related risk stratification based by flow cytometry for patients with de novo angioimmunoblastic T cell lymphoma.

Tumour-infiltrating lymphocytes (TILs) account for a large proportion of tumour microenvironment (TME) in angioimmunoblastic T cell lymphoma (AITL), and at present the significance of TIL in TME of AITL remains unclear. Overall, 50 de novo AITL patients undergoing lymph node flow cytometry from 2014 to 2019 were retrospectively analysed to assess the relationship between TILs and AITL prognosis. We found that high TIL-Bs (≥ 42.4%, p = 0.004) and high CD4:CD8 (≥ 0.85, p = 0.024) were independent favourable prognostic factors for de novo AITL in univariate or multivariate analyses. New TIL-related risk stratification was established based on TIL-Bs and CD4:CD8 factors. Patients in the low-risk group (TIL-Bs ≥ 42.4% and CD4:CD8 ≥ 0.85) had significantly better overall survival than the high-risk (TIL-Bs < 42.4% and CD4:CD8 < 0.85) (p < 0.001) or intermediate-risk group (TIL-Bs ≥ 42.4% and CD4:CD8 < 0.85 or TIL-Bs < 42.4% and CD4:CD8 ≥ 0.85) (p = 0.011). To our knowledge, our cohort is the largest one focusing on the TILs in de novo cases of AITL by analysing lymph node samples using flow cytometry, which is the first time to comprehensively consider humoral immunity and cellular immunity influence on AITL. Our new risk stratification was valuable and useful in evaluating prognosis of AITL and guiding immunotherapy strategies.

Novel risk stratification of de novo diffuse large B cell lymphoma based on tumour-infiltrating T lymphocytes evaluated by flow cytometry.

The prognostic value of tumour-infiltrating T lymphocytes (TIL-Ts) has been demonstrated in many solid tumours but remained unclear in diffuse large B cell lymphoma (DLBCL). We conducted a retrospective cohort study reviewing the TIL-Ts proportion and CD4:CD8 of 66 de novo DLBCL by flow cytometry to construct a risk stratification based on TIL-Ts-related prognostic factors. In univariate analysis, low TIL-Ts (< 14%) was significantly related to shorter survival (HR = 2.58, 95% CI 1.11-5.99, p = 0.028). In multivariate analysis, low TIL-Ts (HR = 6.48, 95% CI 2.16-19.46, p = 0.001) and high CD4:CD8 (> 1.2) (HR = 4.22, 95% CI 1.43-12.35, p = 0.009) were independent risk factors. For the risk stratification, three groups were defined based on TIL-Ts-related risk factors: low-risk group (high TIL-Ts and low CD4:CD8), intermediate risk group (low TIL-Ts, low CD4:CD8 or high TIL-Ts, high CD4:CD8) and high-risk group (low TIL-Ts and high CD4:CD8). The patients in high-risk group have significantly shorter survival than that in intermediate risk group (p = 0.025) and low-risk group (p = 0.002). This new risk stratification which is independent of performance status and age of the patients could hint the prognosis and may guide treatment of DLBCL.

[Expression of TWEAK and Its Receptor CD163 in Peripheral Blood of Psoriasis Vulgaris (PV)].

OBJECTIVE: To investigate serum levels and mRNA expressions of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor CD163 from the patients with psoriasis vulgaris (PV). METHODS: Peripheral blood samples were obtained from 28 patients with PV and 15 healthy control subjects. Serum levels of TWEAK and CD163 were detected by ELISA, mRNA expressions of TWEAK and CD163 in peripheral blood were analyzed by real time-PCR, and protein expressions of TWEAK and CD163 were determined by flow cytometry. RESULTS: All the 28 PV patients were in progressive stage at the beginning of this study, 10 patients then recovered in convalescent stage after treatment. Compared to healthy controls, PV patients had higher serum TWEAK levels and lower serum CD163 levels. Serum TWEAK level in progressive stage was significantly higher than that in convalescent stage. Serum CD163 level were elevated significantly in convalescent stage compared with those in progressive stage. TWEAK mRNA expression in PV patients were significantly lower than that in healthy controls, but there was no significant differences of CD163 mRNA expression. TWEAK expression in monocytes in progressive stage and convalescent stage were significantly higher than that of controls, CD163 expression in monocytes in progressive stage and convalescent stage significantly lower than that in controls. No correlations wene found between psoriasis area and severity index (PASI) score and expression of TWEAK and CD163. CONCLUSION: TWEAK/CD163 pathway may play a role in PV.

The impact of digital economy on rural revitalization: Evidence from Guangdong, China.

Background: Digital technology and economy have profound impact on rural revitalization and become important initiatives to promote rural development. This study analyzes the spatial effect of digital economy on rural revitalization in Guangdong, China. Method: The entropy weight method is used to evaluate the level of rural revitalization and digital economy in 20 prefecture level cities of Guangdong province during 2011-2021. Spatial panel model is used to analyze the spatial spillover effect of digital economy on rural revitalization. Threshold model is employed to analyze the marginal effects of the digital economy on rural revitalization. Heterogeneous analysis is made by grouping the prefecture-level cities into four regions: the Pearl River Delta (PRD), the East Wing, the West Wing and the Mountainous region. Results: Both the level of rural revitalization and digital economy development in every prefecture-level city experienced an increase during 2011-2021 and the PRD region take the lead in both the rural revitalization and digital economy. There is significant spatial spillover effect of digital economy on the rural revitalization as a whole (the coefficient is about 0.3537). However, in the regions with a low level of digital economic development, there is a negative impact (-0.1847) of the digital economy on rural revitalization; while in regions with medium or high level of digital economy, it has a significant positive effect (0.3835) on rural revitalization. The impact of digital economy on rural revitalization development is significantly greater in the PRD (0.3141), the East Wing (0.7215), the West Wing (0.5467) than in the mountainous region (0.2238). Conclusions: There is significant spatial differentiation in the digital economy and rural revitalization. The digital economy has significant spatial spillover effect on the rural revitalization. And this effect is found out to have heterogeneous and non-linear characteristics. In order to promote rural revitalization, it is necessary to make full use of the digital economy and technology in rural areas. Besides, it is important to improve the digital skills and literary of the rural population so that the digital economy could play a greater role in rural revitalization.

High CD8+tumor-infiltrating lymphocytes indicate severe exhaustion and poor prognosis in angioimmunoblastic T-cell lymphoma.

Background: Exhaustion of CD8+ tumor-infiltrating lymphocytes (TILs), characterized by the overexpression of immune checkpoints (IC), is a major impediment to anti-tumor immunity. However, the exhaustion status of CD8+TILs in angioimmunoblastic T cell lymphoma (AITL) remains unclear. Therefore, we aimed to elucidate the exhaustion status of CD8+TILs in AITL and its influence on prognosis. Methods: The correlation between CD8+TILs and IC expression in AITL was analyzed using single-cell RNA sequencing (n = 2), flow cytometry (n = 20), and RNA sequencing (n = 20). Biological changes related to CD8+TILs exhaustion at different cytotoxic T lymphocyte (CTL) levels (mean expression levels of CD8A, CD8B, GZMA, GZMB, and PRF1) in AITL were evaluated using RNA sequencing (n = 20) and further validated using the GEO dataset (n = 51). The impact of CD8 protein expression and CTL levels on patient prognosis was analyzed using flow cytometry and RNA sequencing, respectively. Results: Our findings demonstrated that the higher the infiltration of CD8+TILs, the higher was the proportion of exhausted CD8+TILs characterized by the overexpression of multiple IC. This was accompanied by extensive exhaustion-related biological changes, which suggested severe exhaustion in CD8+TILs and may be one of the main reasons for the poor prognosis of patients with high CD8+TILs and CTL. Conclusion: Our study comprehensively reveals the exhaustion status of CD8+TILs and their potential negative impact on AITL prognosis, which facilitates further mechanistic studies and is valuable for guiding immunotherapy strategies.

Angioimmunoblastic T-Cell Lymphoma Diagnosed From Serous Effusion by Integration of Cytologic Features and Ancillary Studies.

OBJECTIVES: To explore the approach to the diagnosis of malignant serous effusion (SE) caused by angioimmunoblastic T-cell lymphoma (AITL). METHODS: The clinical, cytomorphologic, immunophenotypic, and molecular features of 6 patients were summarized. RESULTS: Clinically, SE caused by AITL was predominant in middle-aged and older male patients with multiple SEs and lymphadenopathy. Cytomorphology showed small to medium-sized, irregular lymphocytes with clear cytoplasm and mixed with various inflammatory cells and apoptosis. Hodgkin/Reed-Sternberg-like cells were detected in 2 of 6 cases. Furthermore, 2 patterns of cytomorphology were described for the first time. Flow cytometry revealed abnormal T-cell populations with loss of surface CD3 (3/4 cases) and CD7 (3/4 cases). In addition, B-cell populations lacking surface immunoglobulin (Ig) were identified in 2 of 4 cases. Immunocytochemical staining revealed expression of at least 2 T follicular helper markers. Epstein-Barr virus-encoded RNA (EBER)-positive cells were demonstrated in 4 of 5 cases. Clonal T-cell receptor γ chain rearrangement was detected in 6 cases, and 3 of them had concomitant clonal immunoglobulin gene rearrangement. Moreover, 2 cases revealed discrepant findings regarding IgH/Igκ rearrangements in cytohistologic correlation. CONCLUSIONS: This study broadens the morphologic spectrum of malignant SE caused by AITL and provides diagnostic criteria in routine practice.

Public trust in the long-term care insurance pilot program in China: An analysis of mediating effects.

Objective: This study aimed to evaluate the implementation of the long-term care insurance (LTCI) pilot program in China through an examination of public trust in the system and its associated factors of insurance awareness and satisfaction with the LTCI policy. Method: An online survey was used to collect data from 786 participants in the city of Guangzhou, one of the pilot sites of the LTCI. Ordinal logistic regression models were used to investigate the related factors of public trust in the LTCI. Structural equation modeling (SEM) was conducted to test the mediating effect of satisfaction with LTCI policy on the relationship between insurance awareness and public trust. Results: More than 60% of participants gave a positive evaluation of the LTCI pilot program. More than 70% of the participants recognized the important role of the program. Both an understanding of insurance and satisfaction with LTCI policies were associated with public trust. The proportion of the indirect effect with regard to the total effect of satisfaction on trust was 70.133%, greater than the direct effect of 29.867%. Conclusions: Our findings supported the hypothesis that satisfaction with the LTCI policy plays a mediating role between insurance awareness and public trust. Optimalization of the LTCI policy was recommended to improve public trust in the LTCI program.

The Impact of Long-Term Care Insurance on Medical Utilization and Expenditures: Evidence from Jingmen, China.

The purpose of this study was to evaluate the impact of long-term care insurance (LTCI) on medical utilization and expenditures in Jingmen, a pilot city of China. The propensity score matching-difference in difference (PSM-DID) approach was employed to examine the expenses and frequency of inpatient and outpatient services before and after the implementation of the LTCI based on the 2015-2018 panel data from the China Health and Retirement Longitudinal Study (CHARLS). The results showed that the annual expenditure and frequency of the inpatient services of Jingmen residents were reduced by 1923 Yuan (287.0 USD) and 0.24 times, respectively. The impact of the LTCI varied between urban and rural areas. The annual expenditure and frequency of inpatient services in rural areas were reduced by 1600 Yuan (238.8 USD) and 0.30 times, which were lower than those (3400 Yuan (507.5 USD) and 0.20 times) in urban areas. The monthly outpatient expenses and frequency in rural areas were reduced by 300 Yuan (44.8 USD) and 0.14 times, but increased by 555 Yuan (82.8 USD) and 0.07 times in urban area. The findings indicated that the implementation of the LTCI can reduce the medical utilization and expenses, and it had a greater effect in rural areas than in urban areas. It is suggested to promote the LTCI nationwide, and more policy preference should be given to the development of the LTCI in rural areas.

Assessing the Sustainability of Long-Term Care Insurance Systems Based on a Policy-Population-Economy Complex System: The Case Study of China.

Although China launched long-term care insurance (LTCI) pilot program in 2016, there are great challenges associated with developing a sustainable LTCI system due to limited financial resources and a rapid increase in the aging population. This study constructed an LTCI policy−population−economics (PPE) system to assess the sustainability of the LTCI system in China. Based on the latest 76 LTCI policy documents published between 2016 and 2021, this study evaluated the strength of LTCI policy modeling in 14 pilot cities by constructing a policy modeling consistency (PMC) index containing 9 main variables and 36 sub-variables. The coupling coordination model was used to evaluate the interaction between LTCI policy, population aging, and economic development. The results showed that the PMC index ranged from 0.527 to 0.850. The policy strength of Qingdao, Nantong, and Shanghai was the highest (PMC > 0.8). Anqing, Qiqihaer, Chongqing, and Chengdu had the lowest level of policy strength (PMC < 0.6). The main policy weaknesses were the coverage of the LTCI, the sources of funds, the scope of care services, and benefit eligibility. The coupling coordination degree of PPE systems varied from 0.429 to 0.921, with a mean of 0.651. Shanghai, Nantong, and Suzhou had the highest level of coordination. The coordination between subsystems of PPE in most pilot cities (12 of 14 cities) was at a basic or low level. The findings from this study concluded that the coordination within the PPE system should be improved to develop a sustainable LTCI system. To improve the coordination of the PPE system, it is suggested that the country should maintain sustainable economic growth and modify LTCI policies based on demographic transitions and economic development.

Comparison of Influence of Blood Pressure and Carotid-Femoral Pulse Wave Velocity on Target Organ Damage in Hypertension.

Objectives: Assessment of target organ damage (TOD) is an important part of the diagnosis and evaluation of hypertension. Carotid-femoral pulse wave velocity (cf-PWV) is considered to be the gold-standard for noninvasive arterial stiffness assessment. This study aims to analyze the risk of TOD in people with different phenotypes of peripheral blood pressure and cf-PWV. Methods: The study cohort was recruited from December 2017 to September 2021 at Ruijin Hospital in Shanghai. It was divided into 4 groups according to peripheral blood pressure (pBP) and cf-PWV. TOD was assessed as carotid intima-media thickness (CIMT), chronic kidney disease (CKD), urinary albumin-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR) and left ventricular mass index (LVMI). Results: A total of 1,257 subjects (mean age 53.13 ± 12.65 years, 64.2% males) was recruited. Age, body mass index (BMI) and fasting blood glucose (FBG), as well as peripheral systolic blood pressure (pSBP), peripheral diastolic blood pressure (pDBP), peripheral pulse pressure (pPP) were significantly different in the four groups (P < 0.01). eGFR, ACR, LVMI and CIMT were significantly different among different groups (P < 0.01). The risk of ACR abnormality was significantly higher in the group with elevated pBP (P = 0.005, OR 2.264, 95%CI 1.277-4.016; and in the group with elevated pBP and cf-PWV (P = 0.003, OR 1.482, 95%CI 1.144-1.920), while left ventricular hypertrophy (LVH) was significantly higher in the group with elevated cf-PWV (P = 0.002, OR 1.868, 95%CI 1.249-2.793). Conclusion: Different profiles based on the status of PBP and cf-PWV associated with different TOD. Individuals with higher pBP have an increased risk of ACR abnormality, while individuals with only cf-PWV elevated have a higher risk of LVH.

Angioimmunoblastic T-cell lymphoma with predominant CD8+ tumor-infiltrating T-cells is a distinct immune pattern with an immunosuppressive microenvironment.

Background: Angioimmunoblastic T-cell lymphoma (AITL) has a rich tumor microenvironment (TME) that typically harbors plenty of CD4+tumor infiltrating lymphocytes, (TIL)-T-cells (so called common AITL). Nonetheless, AITL with large numbers of CD8+TIL-Ts that outnumber CD4+cells have been observed (CD8-predominant AITL). However, detailed comparison of CD8-predominant AITL and common AITL are still lacking. Methods: We compared clinicopathological features, TIL subsets, TME T cell receptor-ß (TRB), and immunoglobulin heavy chain (IGH) repertoires, and gene expression profiles in six CD8-predominant and 12 common AITLs using case-control matching (2014 to 2019). Results: Comparing with common AITLs, CD8-predominant AITLs showed more frequent edema (P = 0.011), effusion (P = 0.026), high elevated plasma EBV-DNA (P = 0.008), and shorter survival (P = 0.034). Moreover, they had more pronounced eosinophil increase (P = 0.004) and a higher Ki67 index (P = 0.041). Flow cytometry revealed an inverted CD4/CD8 ratio in TIL-Ts and lower TIL-B proportions (P = 0.041). TRB repertoire metrics deteriorated, including lower productive clones (P = 0.014) and higher clonality score (P = 0.019). The IGH repertoire was also narrowed, showing a higher proportion of the top 10 clones (P = 0.002) and lower entropy (P = 0.027). Gene expression analysis showed significant enrichment for upregulated negative regulation of immune system processes and downregulated T-cell activation and immune cell differentiation. Conclusion: Our findings demonstrated that CD8-predominant AITL is a distinct immune pattern of AITL characterized by anti-tumor immunity impairment and an immunosuppressive microenvironment. These characteristics can interpret its severe clinical manifestations and poor outcomes.

Effects of MBSR therapy on negative emotions, fatigue, and sleep quality in "post-ICU patients": A randomized controlled clinical trial protocol.

BACKGROUND: Survivors of intensive care unit (ICU) transfer to the common ward are often accompanied by psychological distress, negative emotions, fatigue, and sleep disturbances that affect recovery. Mindfulness-based stress reduction (MBSR) has achieved reliable results in improving physical and mental health. However, no clinical study has been conducted to evaluate the effects of MBSR on negative emotions, fatigue and sleep quality of patients who survived ICU and were transferred to general wards. METHODS: This is a prospective randomized controlled trial (RCT) examining the effects of MBSR on negative emotions, fatigue, and sleep quality in inpatients transferred from ICU to general ward. Participants were randomly divided into the treatment group and the control group in a ratio of 1:1. On the basis of the same nursing plan and health education, the treatment group received MBSR therapy, while the control group received no other interventions, and all the patients were followed up for 3 months after 2 weeks of continuous treatment. The indicators included negative mood indicators [Self-rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS)], fatigue index [Fatigue Severity Scale (FSS) and Brief Fatigue Inventory (BFI)], and sleep quality index [Pittsburgh Sleep Quality Index (PSQI)]. Finally, SPSS 20.0 software was used for statistical analysis of the data. DISCUSSION: This study will evaluate the effects of MBSR on negative emotions, fatigue, and sleep quality in hospitalized patients transferred from ICU to general ward. The results of this study will provide a reference for MBSR to improve psychological distress in ICU survivors transferred to general ward. TRIAL REGISTRATION: This study protocol was registered in the Open Science Framework (OSF) (registration number: DOI 10.17605/OSF.IO/PD7SU).

Interactions of Bacterial Toxin CNF1 and Host JAK1/2 Driven by Liquid-Liquid Phase Separation Enhance Macrophage Polarization.

Urinary tract infections (UTIs) are a global public health concern, which is mainly caused by uropathogenic Escherichia coli (UPEC). Cytotoxic necrotizing factor 1 (CNF1) is a key UPEC toxin and regulates multiple host cellular processes through activating the Rho GTPases; however, the effect of CNF1 on macrophage polarization remains unknown. Here, we found that CNF1 promoted M1 macrophage polarization through regulating NF-κB and JAK-STAT1 signaling pathways in kidney at an early stage of acute UTIs. Notably, we identified CNF1 could directly interact with JAK1/2 through its domain without Rho GTPases activation, which induced JAK1/2 phosphorylation, subsequent STAT1 activation and M1 polarization. Moreover, CNF1 exhibited liquid-liquid phase separation (LLPS) to induce a CNF1-JAK1/2 complex, promoting macrophage reprogramming. These findings highlight the LLPS-dependent and Rho GTPase-independent effect of CNF1 as an adaptor on interfering with host cell signals. IMPORTANCE CNF1 is a key toxin secreted by UPEC, which induces inflammation during UPEC infections. CNF1 is well known to activate Rho GTPases to disturb host cell signaling pathways. Macrophage reprogramming plays important roles in inflammation; however, the effect of CNF1 on macrophage polarization is not reported. This study demonstrated the role and mechanism of CNF1 in promoting M1 macrophage polarization during UPEC-induced acute kidney infections. Importantly, we identified Rho GTPase-independent effect of CNF1 as an adaptor on interfering with host cell signals and demonstrated that CNF1 exhibited LLPS to drive its interaction with host proteins, which improve our understanding of the UPEC-host interactions and UTI pathogenesis.

Flow Cytometry-Assessed PD1/PDL1 Status in Tumor-Infiltrating Lymphocytes: A Link With the Prognosis of Diffuse Large B-Cell Lymphoma.

The PD1/PDL1 status of tumor-infiltrating lymphocytes (TILs) in diffuse large B-cell lymphoma (DLBCL) reflects immune function. However, the previously reported methods for evaluating this status are complex and may not be widely used in clinical practice. In addition, these studies did not introduce healthy controls to designate the cut-off when evaluating the prognostic value of the status. In this study, we retrospectively evaluated the PD1/PDL1 status in TILs of 24 DLBCL tissue samples and normal immune cells in 61 demographically matched healthy controls (tissue samples from patients with reactive hyperplasia [RH]) by flow cytometry. We investigated the prognostic value of the PD1/PDL1 status in TILs by precisely determining the cut-off value and assessing the reliability of flow cytometry. The mean fluorescence intensity (MFI) of PD1 in TIL-T-cells (TIL-Ts; median, 110) and CD8+TIL-Ts (median, 64) was significantly higher than that of CD3+T-cells (median, 64) and CD8+ T-cells (median, 34) in RH. The cut-off values of PD1/PDL1 status for analyzing prognostic values were defined considering the PD1/PDL1 status of samples from both patients with DLBCL and healthy controls. High MFI of PD1 in TIL-Ts (MFI >108, P = 0.022), high proportion of PD1+CD4+TIL-Ts (>1.1% of CD4+TIL-Ts, P = 0.049), high proportion of PD1+CD8+TIL-Ts (>2% of CD8+TIL-Ts, P = 0.025), and high MFI of PDL1 in TIL-Ts (MFI >83, P = 0.023) were risk factors for inferior prognosis of DLBCL. Our results indicate that flow cytometry is a reliable and convenient method for evaluating the immune-checkpoint status of TILs, which probably holds major implications in clinical practice.

Facile Synthesis of Phosphorus and Cobalt Co-Doped Graphitic Carbon Nitride for Fire and Smoke Suppressions of Polylactide Composite.

Due to the unique two-dimensional structure and features of graphitic carbon nitride (g-C3N4), such as high thermal stability and superior catalytic property, it is considered to be a promising flame retardant nano-additive for polymers. Here, we reported a facile strategy to prepare cobalt/phosphorus co-doped graphitic carbon nitride (Co/P-C3N4) by a simple and scalable thermal decomposition method. The structure of Co/P-C3N4 was confirmed by scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The carbon atoms in g-C3N4 were most likely substituted by phosphorous atoms. The thermal stability of polylactide (PLA) composites was increased continuously with increasing the content of Co/P-C3N4. In contrast to the g-C3N4, the Polylactide (PLA) composites containing Co/P-C3N4 exhibited better flame retardant efficiency and smoke suppression. With the addition of 10 wt % Co/P-C3N4, the peak heat release rate (PHRR), carbon dioxide (CO2) production (PCO2P) and carbon oxide (CO) production (PCOP) values of PLA composites decreased by 22.4%, 16.2%, and 38.5%, respectively, compared to those of pure PLA, although the tensile strength of PLA composites had a slightly decrease. The char residues of Co/P-C3N4 composites had a more compact and continuous structure with few cracks. These improvements are ascribed to the physical barrier effect, as well as catalytic effects of Co/P-C3N4, which inhibit the rapid release of combustible gaseous products and suppression of toxic gases, i.e., CO.