Sporophytic control of tapetal development and pollen fertility by a mitogen-activated protein kinase cascade in rice.

Tapetum, the innermost layer of the anther wall, provides essential nutrients and materials for pollen development. Timely degradation of anther tapetal cells is a prerequisite for normal pollen development in flowering plants. Tapetal cells facilitate male gametogenesis by providing cellular contents after highly coordinated programmed cell death (PCD). Tapetal development is regulated by a transcriptional network. However, the signaling pathway(s) involved in this process are poorly understood. In this study, we report that a mitogen-activated protein kinase (MAPK) cascade composed of OsYDA1/OsYDA2-OsMKK4-OsMPK6 plays an important role in tapetal development and male gametophyte fertility. Loss of function of this MAPK cascade leads to anther indehiscence, enlarged tapetum, and aborted pollen grains. Tapetal cells in osmkk4 and osmpk6 mutants exhibit an increased presence of lipid body-like structures within the cytoplasm, which is accompanied by a delayed occurrence of PCD. Expression of a constitutively active version of OsMPK6 (CA-OsMPK6) can rescue the pollen defects in osmkk4 mutants, confirming that OsMPK6 functions downstream of OsMKK4 in this pathway. Genetic crosses also demonstrated that the MAPK cascade sporophyticly regulates pollen development. Our study reveals a novel function of rice MAPK cascade in plant male reproductive biology.

DNAJC24 acts directly with PCNA and promotes malignant progression of LUAD by activating phosphorylation of AKT.

Heat shock proteins (HSPs) are a group of highly conserved proteins found in a wide range of organisms. In recent years, members of the HSP family were overexpressed in various tumors and widely involved in oncogenesis, tumor development, and therapeutic resistance. In our previous study, DNAJC24, a member of the DNAJ/HSP40 family of HSPs, was found to be closely associated with the malignant phenotype of hepatocellular carcinoma. However, its relationship with other malignancies needs to be further explored. Herein, we demonstrated that DNAJC24 exhibited upregulated expression in LUAD tissue samples and predicted poor survival in LUAD patients. The upregulation of DNAJC24 expression promoted proliferation and invasion of LUAD cells in A549 and NCI-H1299 cell lines. Further studies revealed that DNAJC24 could regulate the PI3K/AKT signaling pathway by affecting AKT phosphorylation. In addition, a series of experiments such as Co-IP and mass spectrometry confirmed that DNAJC24 could directly interact with PCNA and promoted the malignant phenotypic transformation of LUAD. In conclusion, our results suggested that DNAJC24 played an important role in the progression of LUAD and may serve as a specific prognostic biomarker for LUAD patients. The DNAJC24/PCNA/AKT axis may be a potential target for future individualized and precise treatment of LUAD patients.

Dynamic change in red cell distribution width as a predictor for short-time mortality in dermatomyositis-associated rapid progressive interstitial lung disease.

AIM: We aimed to explore a new and readily available practical marker for rapidly progressive interstitial lung disease (RP-ILD) and poor short-term outcomes in patients with idiopathic inflammatory myopathies (IIM). METHODS: A total of 1822 consecutive patients with IIM between 2009 and 2021 were evaluated retrospectively. All proven cases of naïve ILD with complete medical records were included. Red cell distribution width (RDW) values at the initial stage, 3 months and last follow-up were collected. The clinical characteristics and outcomes of the patients were recorded. RESULTS: We identified 532 patients with IIM with an average follow-up of 4 years. ILD prevalence was higher in patients of elevated RDW (p<0.001). The patients with ILD and elevated RDW had lower levels of PaO2/FiO2, FVC% and DLco% and a higher prevalence of RP-ILD than those with normal RDW (p<0.001). Prognostic analysis revealed that RDW was an independent risk factor for prognosis in patients with IIM-ILD (HR=2.9, p=0.03). Patients with dermatomyositis (DM) with RP-ILD with a change in RDW within 3 months (∆RDW-3) greater than 0 were more likely to die within 3 months. Moreover, the prevalence of ∆RDW-3>0 was higher in patients with RP-ILD and positive for anti-melanoma differentiation-associated gene 5 antibody who died within 3 months (87.5%) compared with those alive at 3 months (24.6%) (p<0.001). CONCLUSION: These findings suggest that repeated RDW assays could assist physicians in identifying patients with DM-ILD who were at a high risk of RP-ILD and death.

ACOX1 deficiency-induced lipid metabolic disorder facilitates chronic interstitial fibrosis development in renal allografts.

Chronic interstitial fibrosis presents a significant challenge to the long-term survival of transplanted kidneys. Our research has shown that reduced expression of acyl-coenzyme A oxidase 1 (ACOX1), which is the rate-limiting enzyme in the peroxisomal fatty acid ß-oxidation pathway, contributes to the development of fibrosis in renal allografts. ACOX1 deficiency leads to lipid accumulation and excessive oxidation of polyunsaturated fatty acids (PUFAs), which mediate epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) reorganization respectively, thus causing fibrosis in renal allografts. Furthermore, activation of Toll-like receptor 4 (TLR4)-nuclear factor kappa-B (NF-κB) signaling induced ACOX1 downregulation in a DNA methyltransferase 1 (DNMT1)-dependent manner. Overconsumption of PUFA resulted in endoplasmic reticulum (ER) stress, which played a vital role in facilitating ECM reorganization. Supplementation with PUFAs contributed to delayed fibrosis in a rat model of renal transplantation. The study provides a novel therapeutic approach that can delay chronic interstitial fibrosis in renal allografts by targeting the disorder of lipid metabolism.

A Retrospective Study on Predicting Recurrence of Intermediate-Stage Hepatocellular Carcinoma After Radical Therapy.

Purpose: This study aimed to investigate the potential benefits of radical therapy in patients with stage B disease. Patients and Methods: A retrospective analysis was conducted on a cohort of 437 patients diagnosed with stage B hepatocellular carcinoma, who underwent either hepatic resection (HR) or radiofrequency ablation (RFA) at the Cancer Institute and Hospital of Tianjin Medical University from May 2011 to May 2022. Multivariate COX regression analysis was performed to identify the independent prognostic factors related to recurrence-free survival (RFS). The performance of the developed nomogram was evaluated using various statistical measures, including the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: Multivariate analysis revealed that tumor diameter, number of tumors, number of involved liver segments, alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), lactate dehydrogenase (LDH), and systemic immune inflammation index (SII) were independent prognostic factors influencing patients' RFS, and these factors were incorporated into the nomogram. The C-index of the nomogram in the training cohort was 0.721, and the AUC at 2 and 3 years was 0.772 and 0.790, respectively. These values were appreciably higher than commonly used clinic staging systems and other predictive models. The calibration curve and DCA demonstrated good calibration and net benefit. Survival analysis comparing stage B patients who received radical treatment with stage A patients with multiple lesions did not reveal a significant difference in Kaplan-Meier survival curves (P=0.91). Conclusion: The nomogram provided a precise prediction of the recurrence for stage B hepatocellular carcinoma patients undergoing radical treatment. Furthermore, certain stage B patients may benefit from radical treatment.

[Retracted] Total flavonoids suppress lung cancer growth via the COX­2­mediated Wnt/ß­catenin signaling pathway.

[This retracts the article DOI: 10.3892/ol.2020.11271.].

Targeted changes in blood lipids improves fibrosis in renal allografts.

BACKGROUND: Chronic interstitial fibrosis is the primary barrier against the long-term survival of transplanted kidneys. Extending the lifespan of allografts is vital for ensuring the long-term health of patients undergoing kidney transplants. However, few targets and their clinical applications have been identified. Moreover, whether dyslipidemia facilitates fibrosis in renal allograft remains unclear. METHODS: Blood samples were collected from patients who underwent kidney transplantation. Correlation analyses were conducted between the Banff score and body mass index, and serum levels of triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. A rat model of renal transplantation was treated with the lipid-lowering drug, fenofibrate, and kidney fibrosis levels were determined by histochemical staining. Targeted metabolomic detection was conducted in blood samples from patients who underwent kidney transplantation and were divided into fibrotic and non-fibrotic groups. Rats undergoing renal transplantation were fed either an n-3 or n-6 polyunsaturated fatty acid (PUFA)-enriched diet. Immunohistochemical and Masson's trichrome staining were used to determine the degree of fibrosis. RESULTS: Hyperlipidemia was associated with fibrosis development. Treatment with fenofibrate contributed to improve fibrosis in a rat model of renal transplantation. Moreover, n-3 PUFAs from fibrotic group showed significant downregulation compared to patients without fibrotic renal allografts, and n-3 PUFAs-enriched diet contributed to delayed fibrosis in a rat model of renal transplantation. CONCLUSIONS: This study suggests that hyperlipidemia facilitates fibrosis of renal allografts. Importantly, a new therapeutic approach was provided that may delay chronic interstitial fibrosis in transplanted kidneys by augmenting the n-3 PUFA content in the diet.

Overexpression of FNDC4 constrains ovarian cancer progression by promoting cell apoptosis and inhibiting cell growth.

Hepatocellular carcinoma is one of the most common malignant tumors in the world. It has been reported that fibronection type III domain containing family plays an important role in the formation and development of a variety of tumors, but the role of FNDC4 is still unclear. In our study, we found that FNDC4 was highly expressed in normal liver tissues but abnormally expressed at low levels in liver cancer tissues. Enhanced apoptosis and decreased proliferation were shown in the FNDC4 overexpression model in HepG2 cells. In addition, FNDC4 was negatively correlated with AFP, a tumor marker of HCC, and other cancer-related genes such as AHSA1, GDF1, GPC3 and MDK. In addition, we found that FNDC4 was associated with the abundance of several tumor-infiltrating lymphocytes and the expression of chemokines and immunostimulators, and FNDC4 was enriched in response to transforming growth factor ß. These results indicated that FNDC4 plays a key role in hepatocellular carcinoma progression and might be a promising biomarker for cancer diagnosis.

Lenvatinib plus sintilimab with or without transarterial chemoembolization for intermediate or advanced stage hepatocellular carcinoma: a propensity score-matching cohort study.

In this retrospective study, we compared the efficacy and safety of lenvatinib plus sintilimab, with or without transarterial chemoembolization (TLS vs. LS), in patients with intermediate or advanced stage hepatocellular carcinoma (HCC). Eligible patients who received combination therapy with TLS or LS at Tianjin Medical University Cancer Institute & Hospital from December 2018 to October 2020 were propensity score matched (PSM) to correct for potential confounding biases between the two groups. The primary endpoint was progression-free survival (PFS) and secondary endpoints were overall survival (OS), overall response rate (ORR) and treatment-related adverse events (TRAEs). Cox proportional hazards models were used to identify prognostic factors. The study included 152 patients (LS group, n=54, TLS group, n=98). After PSM, patients in the TLS group had significantly longer PFS (11.1 versus 5.1 months, P=0.033), OS (not reached versus 14.0 months, P=0.0039) and ORR (modified Response Evaluation Criteria in Solid Tumors: 44.0% versus 23.1%; P=0.028) than those in the LS group. In the multivariate Cox regression analysis, the treatment regimen (TLS versus LS) was an independent predictor for both PFS (HR=0.551; 95% CI: 0.334-0.912; P=0.020) and OS (HR=0.349; 95% CI: 0.176-0.692; P=0.003) and CA19-9 level was an independent predictor for OS (HR=1.005; 95% CI: 1.002-1.008; P=0.000). No significant differences in the incidence of grade ≥3 TRAEs were reported between the two treatment groups. In conclusion, triple combination therapy with TLS improved survival with an acceptable safety profile compared with LS in patients with intermediate or advanced stage HCC.

A comprehensive evaluation of full-spectrum cell-free RNAs highlights cell-free RNA fragments for early-stage hepatocellular carcinoma detection.

BACKGROUND: Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently validated, and some results are contradictory. We provided a comprehensive evaluation of various types of cfRNA biomarkers and a full mining of the biomarker potential of new features of cfRNA. METHODS: We first systematically reviewed reported cfRNA biomarkers and calculated dysregulated post-transcriptional events and cfRNA fragments. In 3 independent multicentre cohorts, we further selected 6 cfRNAs using RT-qPCR, built a panel called HCCMDP with AFP using machine learning, and internally and externally validated HCCMDP's performance. FINDINGS: We identified 23 cfRNA biomarker candidates from a systematic review and analysis of 5 cfRNA-seq datasets. Notably, we defined the cfRNA domain to describe cfRNA fragments systematically. In the verification cohort (n = 183), cfRNA fragments were more likely to be verified, while circRNA and chimeric RNA candidates were neither abundant nor stable as qPCR-based biomarkers. In the algorithm development cohort (n = 287), we build and test the panel HCCMDP with 6 cfRNA markers and AFP. In the independent validation cohort (n = 171), HCCMDP can distinguish HCC patients from control groups (all: AUC = 0.925; CHB: AUC = 0.909; LC: AUC = 0.916), and performs well in distinguishing early-stage HCC patients (all: AUC = 0.936; CHB: AUC = 0.917; LC: AUC = 0.928). INTERPRETATION: This study comprehensively evaluated full-spectrum cfRNA biomarker types for HCC detection, highlighted the cfRNA fragment as a promising biomarker type in HCC detection, and provided a panel HCCMDP. FUNDING: National Natural Science Foundation of China, and The National Key Basic Research Program (973 program).

Incidence, mortality, and risk factors of acute kidney injury after immune checkpoint inhibitors: Systematic review and meta-analysis of real-world evidence.

BACKGROUND: To precisely quantify the incidence, mortality, and risk factors for acute kidney injury (AKI) following immune checkpoint inhibitor (ICI) treatment for cancer in real-world scenarios. METHODS: Comprehensive searches were performed on PubMed, EMBASE and the Cochrane library. Real-world observational studies reporting incidence, mortality and/or factors for AKI in ICI-treated patients were eligible. Odds ratio (OR) with 95% CI for potential predictors and hazard ratio (HR) with 95% CI for mortality risk associated with AKI were calculated using the random-effect model. RESULTS: Eighteen articles comprising 12,111 patients receiving ICI were finally eligible. The pooled incidence was 16.0% (95% CI 11.2%-20.8%; n = 15) for AKI following ICI therapies overall and 3.5% (95% CI 2.1%-4.9%; n = 8) for ICI-induced AKI. Patients who developed AKI during ICI therapies had 51% increased risk of death compared with those without (HR 1.51, 95% CI 1.07-2.14). Regarding risk factors, statistically increased risk for AKI during ICI therapies was observed with preexisting chronic kidney diseases (OR 1.86, 1.25-2.78), diabetes (OR 1.26, 1.04-1.53), and concomitant extrarenal immune-related adverse events (OR 2.53, 1.79-3.56). Ipilimumab (OR 2.18, 1.43-3.32), combined ICI therapies (OR 1.80, 1.14-2.83) and concomitant use of proton pump inhibitors (OR 1.97, 1.56-2.49), renin-angiotensin system inhibitors (OR 1.50, 1.05-2.14), diuretics (OR 1.69, 1.27-2.26) also significantly predicted the incident AKI. CONCLUSIONS: AKI episode is frequently observed during ICI exposure for cancer treatment, but ICI induced nephrotoxicity is only occasionally. Higher risk of AKI during ICI therapies was significantly associated with specific comorbidities, concomitant of certain drugs, ipilimumab and ICI combination therapies.

The Recent Outbreak of COVID-19 in China During the Omicron Variant Predominance: Clinical Features and Outcomes in Patients with Autoimmune Inflammatory Rheumatic Diseases.

INTRODUCTION: The impact of coronavirus disease 2019 (COVID-19) on vulnerable populations with autoimmune inflammatory rheumatic diseases (AIIRDs) has been variable with variants and of great concern. Here we report the clinical features, outcomes, and risk factors for infection and hospitalization in patients with AIIRDs in the first wave of infection in China in December 2022. METHODS: A real-world survey was conducted in Chinese patients with AIIRDs from 8 December 2022 to 13 January 2023. The survey was distributed via internet nationwide, clinic consultation, and to inpatients at a tertiary hospital in Beijing. Clinical features, outcomes, and vaccination status were collected. RESULTS: A total of 2005 patients with AIIRDs completed the survey. There were 1690 (84.3%) patients infected and only 48.2% of patients received COVID-19 vaccination. Most of the fully vaccinated patients received inactivated COVID-19 vaccines, including Sinovac (55.6%) and Sinopharm (27.2%), followed by recombinant subunit vaccine from Zhifei Longcom (2.0%). The independent protecting factors for infection were a time interval of less than 3 months from last vaccination (OR 0.53, p = 0.037) and rheumatoid arthritis (RA) as the underlying AIIRD (OR 0.62, p = 0.041). A total of 57 out of 1690 patients (3.4%) were hospitalized for COVID, with 46 (2.7%) experiencing severe/critical course and 6 deaths (0.4%). In multivariable logistic regression analysis, independent risk factors for hospitalization were age over 60 years (OR 11.52, p < 0.001), with comorbidity (OR 1.83, p = 0.045) and systemic lupus erythematosus (SLE) as the AIIRDs (OR 2.59, p = 0.036). Receiving booster vaccine was an independent protective factor for hospitalization (OR 0.53, 95% CI 0.30-0.98; p = 0.018). CONCLUSION: Hesitation for vaccination is common among Chinese patients with AIIRDs. The time from last vaccination of less than 3 months and having RA decreased the risk of COVID infection. Older age and having comorbidity or SLE increased the risk of hospitalization, while booster vaccination reduced the risk.

TWF1 induces autophagy and accelerates malignant phenotype in lung adenocarcinoma via inhibiting the cAMP signaling pathway.

Many studies have shown that the actin cytoskeleton plays an essential role in the initiation and progression of cancer. As an actin-binding protein, Twinfilin1 (TWF1) plays an important role in regulating cytoskeleton-related functions. However, little is known about the expression and function of TWF1 in human tumors. The present study aimed to investigate the functional roles and the underlying molecular mechanisms of TWF1 in human lung adenocarcinoma (LUAD). By using bioinformatics databases and tumor tissues, TWF1 expression was found to be higher in LUAD tissues than in adjacent tissues and poor survival was predicted in patients with LUAD. In vitro and in vivo assays indicated that downregulation of TWF1 expression suppressed LUAD cells invasion and migration. Further studies revealed that TWF1 interacted with p62 and was involved in the regulation of autophagy. The molecular mechanisms underlying TWF1 were investigated by RNA-seq analysis and a series of functional experiments. The results showed that downregulation of TWF1 suppressed LUAD progression through the cAMP signaling pathway. Therefore, overexpression of TWF1 in LUAD promoted migration, invasion, and autophagy through the cAMP signaling pathway.

A Retrospective Analysis of Conversion Therapy with Lenvatinib, Sintilimab, and Arterially-Directed Therapy in Patients with Initially Unresectable Hepatocellular Carcinoma.

Purpose: The purpose of this study was to investigate the triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy as a conversion therapy for initially unresectable hepatocellular carcinoma (HCC). Patients and Methods: We retrospectively analyzed data from all HCC patients who underwent lenvatinib plus sintilimab plus arterially-directed therapy at Tianjin Medical University Cancer Hospital between December 2018 and October 2020. Of 98 enrolled patients, 37 patients were classified as potentially resectable. We compared the potentially resectable population (PRP) with the non-potentially resectable population (NPRP). The primary study endpoint was conversion rate, and secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: The baseline characteristics were comparable between populations except for a higher proportion of patients with extrahepatic metastases in the NPRP versus PRP (23/61 [37.7%] vs 3/37 [8.1%], respectively; p=0.003). For PRP, the ORR was 67.6% based on RECIST v1.1 (75.7% based on mRECIST), conversion rate was 40.5% (15/37). Of the 15 patients who underwent surgical resection, three achieved complete pathological remission. The median follow-up for all patients was 28 months (range: 2-47). For NPRP, the ORR was 22.9% based on RECIST v1.1 (31.1% based on mRECIST), The median PFS for PRP was significantly longer than that of NPRP (25 vs 13 months, p = 0.0025). The median OS for PRP was significantly longer than that of NPRP (not reached VS 21 months, p=0.014). Hypertension was the most common grade ≥3 adverse reaction in both PRP and NPRP. No new safety signals were observed for any of the treatments. Conclusion: The triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy can convert potentially unresectable HCC into resectable disease and improve long-term survival.

Visual demonstration and prediction of the Hofmeister series based on a poly(ionic liquid) photonic array.

The Hofmeister effect and associated Hofmeister series (HS) are ubiquitous in physicochemical phenomena and have demonstrated fundamental importance in a myriad of fields ranging from chemistry to biology. Visualization of the HS not only helps to straightforwardly understand the underpinning mechanism, but also enables the prediction of new ion positions in the HS and directs the applications of the Hofmeister effect. Owing to the difficulties of sensing and reporting complete multiple and subtle inter- and intramolecular interactions involved in the Hofmeister effect, facile and accurate visual demonstration and prediction of the HS remain highly challenging. Herein, a poly(ionic liquid) (PIL)-based photonic array containing 6 inverse opal microspheres was rationally constructed to efficiently sense and report the ion effects of the HS. The PILs can not only directly conjugate with HS ions due to their ion-exchange properties, but also provide sufficient noncovalent binding diversity with these ions. Meanwhile, subtle PIL-ion interactions can be sensitively amplified to optical signals owing to their photonic structures. Therefore, synergistic integration of PILs and photonic structures gives rise to accurate visualization of the ion effect of the HS, as demonstrated by correctly ranking 7 common anions. More importantly, assisted by principal component analysis (PCA), the developed PIL photonic array can serve as a general platform to facilely, accurately, and robustly predict the HS positions of an unprecedented amount of important and useful anions and cations. These findings indicate that the PIL photonic platform is very promising for addressing challenges in the visual demonstration and prediction of HS and promoting a molecular-level understanding of the Hoffmeister effect.

Advances of Research on Dual-Frequency Solid-State Lasers for Synthetic-Wave Absolute-Distance Interferometry.

Frequency-difference-stabilized dual-frequency solid-state lasers with tunable and large frequency difference have become an ideal light source for the high-accuracy absolute-distance interferometric system due to their stable multistage synthetic wavelengths. In this work, the advances in research on oscillation principles and key technologies of the different kinds of dual-frequency solid-state lasers are reviewed, including birefringent dual-frequency solid-state lasers, biaxial and two-cavity dual-frequency solid-state lasers. The system composition, operating principle, and some main experimental results are briefly introduced. Several typical frequency-difference stabilizing systems for dual-frequency solid-state lasers are introduced and analyzed. The main development trends of research on dual-frequency solid-state lasers are predicted.

Flare and change in disease activity among patients with stable rheumatoid arthritis following coronavirus disease 2019 vaccination: A prospective Chinese cohort study.

BACKGROUND: Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA). METHODS: A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups. RESULTS: A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment ( P  = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred. CONCLUSIONS: COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.

Urbanization can accelerate climate change by increasing soil N2 O emission while reducing CH4 uptake.

Urban land-use change has the potential to affect local to global biogeochemical carbon (C) and nitrogen (N) cycles and associated greenhouse gas (GHG) fluxes. We conducted a meta-analysis to (1) assess the effects of urbanization-induced land-use conversion on soil nitrous oxide (N2 O) and methane (CH4 ) fluxes, (2) quantify direct N2 O emission factors (EFd ) of fertilized urban soils used, for example, as lawns or forests, and (3) identify the key drivers leading to flux changes associated with urbanization. On average, urbanization increases soil N2 O emissions by 153%, to 3.0 kg N ha-1  year-1 , while rates of soil CH4 uptake are reduced by 50%, to 2.0 kg C ha-1  year-1 . The global mean annual N2 O EFd of fertilized lawns and urban forests is 1.4%, suggesting that urban soils can be regional hotspots of N2 O emissions. On a global basis, conversion of land to urban greenspaces has increased soil N2 O emission by 0.46 Tg N2 O-N year-1 and decreased soil CH4 uptake by 0.58 Tg CH4 -C year-1 . Urbanization driven changes in soil N2 O emission and CH4 uptake are associated with changes in soil properties (bulk density, pH, total N content, and C/N ratio), increased temperature, and management practices, especially fertilizer use. Overall, our meta-analysis shows that urbanization increases soil N2 O emissions and reduces the role of soils as a sink for atmospheric CH4 . These effects can be mitigated by avoiding soil compaction, reducing fertilization of lawns, and by restoring native ecosystems in urban landscapes.

AIE-doped Poly(Ionic Liquid) Photonic Spheres for the Discrimination of Psychoactive Substances.

Drugs of abuse has drawn intense attention due to increasing concerns to public health and safety. The construction of a sensing platform with the capability to identify them remains a big challenge because of the limitations of synthetic complexity, sensing scope and receptor extendibility. Here a kind of poly(ionic liquid) (PIL) photonic crystal spheres doped with aggregation-induced emission (AIE) luminogens was developed. As diverse noncovalent interactions involve in PIL moieties, the single sphere shows different binding affinity to a broad range of psychoactive substances. Furthermore, the dual-channel signals arising from photonic crystal structures and sensitive AIE-luminogens provide high-dimensional information for discriminative detection of targets, even for molecules with slight structural differences. More importantly, such single sphere sensing platform could be flexibly customized through ion-exchange, showing great extendibility to fabricate high-efficiency/high-throughput sensing arrays without tedious synthesis.