Impact of three-dimensional-printing technology guidance on surgical outcomes for retroperitoneal sarcoma: A propensity score-matched study.

BACKGROUND: The surgical treatment of retroperitoneal sarcoma (RPS) is highly challenging because of its complex anatomy. In this study, the authors compared the surgical outcomes of patients with RPS who underwent surgical resection guided by three-dimensional (3D) printing technology versus traditional imaging. METHODS: This retrospective study included 251 patients who underwent RPS resection guided by 3D-printing technology or traditional imaging from January 2019 to December 2022. The main outcome measures were operative time, intraoperative blood loss, postoperative complications, and hospital stay. RESULTS: In total, 251 patients were enrolled in the study: 46 received 3D-printed navigation, and 205 underwent traditional surgical methods. Propensity score matching yielded 44 patients in the 3D group and 82 patients in the control group. The patients' demographics and tumor characteristics were comparable in the matched cohorts. The 3D group had significantly shorter operative time (median, 186.5 minutes [interquartile range (IQR), 130.0-251.3 minutes] vs. 210.0 minutes [IQR, 150.8-277.3 minutes]; p = .04), less intraoperative blood loss (median, 300.0 mL [IQR, 100.0-575.0 mL] vs. 375.0 mL [IQR, 200.0-925.0 mL]; p = .02), shorter postoperative hospital stays (median, 11.0 days [IQR, 9.0-13.0 days] vs. 14.0 days [IQR, 10.8-18.3 days]; p = .02), and lower incidence rate of overall postoperative complications than the control group (18.1% vs. 36.6%; p = .03). There were no differences with regard to the intraoperative blood transfusion rate, the R0/R1 resection rate, 30-day mortality, or overall survival. CONCLUSIONS: Patients in the 3D group had favorable surgical outcomes compared with those in the control group. These results suggest that 3D-printing technology might overcome challenges in RPS surgical treatment. PLAIN LANGUAGE SUMMARY: The surgical treatment of retroperitoneal sarcoma (RPS) is highly challenging because of its complex anatomy. The purpose of this study was to investigate whether three-dimensional (3D) printing technology offers advantages over traditional two-dimensional imaging (such as computed tomography and magnetic resonance imaging) for guiding the surgical treatment of RPS. In a group of patients who had RPS, surgery guided by 3D-printing technology was associated with better surgical outcomes, including shorter operative time, decreased blood loss, shorter hospital stays, and fewer postoperative complications. These findings suggested that 3D-printing technology could help surgeons overcome challenges in the surgical treatment of RPS. 3D-printing technology has important prospects in the surgical treatment of RPS.

Long-Term Outcomes of the Self-Expandable Metallic Stent as a Bridge to Surgery versus Elective Surgery without Stent Placement for Colorectal Cancer: A Retrospective Cohort Study.

BACKGROUND: The uncertainty surrounding whether delaying surgery after self-expandable metal stent (SEMS) placement for neoplastic stricture can yield similar oncologic outcomes as elective surgery remains. This study aims to investigate the impact of elective surgery following SEMS placement for obstructive colorectal cancer (OCC) on patients. METHODS: Patients diagnosed with stage I to III colorectal cancer (CRC) were recruited and randomly allocated into two groups: group A, receiving elective surgery after SEMS placement for obstructive colon cancer, and group B, undergoing elective surgery for non-obstructive colorectal cancer. Following a 1:2 matching process based on age, gender, tumor location, tumor depth, pathological stage, and adjuvant chemotherapy, group A comprised 95 patients, while group B consisted of 190 patients for comparative analysis. RESULTS: The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were worse in group A (62.3% vs. 70.9%, p = 0.086) and (65.6% vs. 75.8%, p = 0.093) compared with group B, although these differences were not statistically significant. This discrepancy in long-term oncologic outcomes did not reach significance when the analysis was stratified by tumor perineural invasion (PNI) status. Univariate analysis revealed that SEMS placement was not a poor prognostic factor for DFS (p = 0.086). CONCLUSIONS: Elective surgery for obstructive colorectal cancer (OCC) following SEMS placement may exhibit poorer long-term oncologic outcomes compared to elective surgery for non-obstructive colorectal cancer, particularly due to the higher rate of PNI associated with OCC. Upon stratification of patients in each group by PNI status, the observed differences became marginal.

Emerging roles of ferroptosis in pulmonary fibrosis: current perspectives, opportunities and challenges.

Pulmonary fibrosis (PF) is a chronic interstitial lung disorder characterized by abnormal myofibroblast activation, accumulation of extracellular matrix (ECM), and thickening of fibrotic alveolar walls, resulting in deteriorated lung function. PF is initiated by dysregulated wound healing processes triggered by factors such as excessive inflammation, oxidative stress, and coronavirus disease (COVID-19). Despite advancements in understanding the disease's pathogenesis, effective preventive and therapeutic interventions are currently lacking. Ferroptosis, an iron-dependent regulated cell death (RCD) mechanism involving lipid peroxidation and glutathione (GSH) depletion, exhibits unique features distinct from other RCD forms (e.g., apoptosis, necrosis, and pyroptosis). Imbalance between reactive oxygen species (ROS) production and detoxification leads to ferroptosis, causing cellular dysfunction through lipid peroxidation, protein modifications, and DNA damage. Emerging evidence points to the crucial role of ferroptosis in PF progression, driving macrophage polarization, fibroblast proliferation, and ECM deposition, ultimately contributing to alveolar cell death and lung tissue scarring. This review provides a comprehensive overview of the latest findings on the involvement and signaling mechanisms of ferroptosis in PF pathogenesis, emphasizing potential novel anti-fibrotic therapeutic approaches targeting ferroptosis for PF management.

Survival analysis in pT1-3 and paracolic lymph-node invasion colorectal cancer: the prognostic role of positive paracolic lymph-node ratio for adjuvant chemotherapy.

PURPOSE: Several studies have observed that some stage III colorectal cancer (CRC) patients cannot benefit from standard adjuvant chemotherapy. However, there is no unified screening standard to date. METHODS: Consecutive patients with pathologically confirmed colon adenocarcinoma treated in 3 centers between January 2016 and December 2018 were included. Patients were divided into four groups according to different stages and positive paracolic lymph-node ratio (P-LNR) [Cohort 1: pT1-3N0M0, Cohort 2: pT1-3N + (P-LNR ≤ 0.15)M0, Cohort 3: pT4N0M0, Cohort 4: stage III patients except for pT1-3N + (P-LNR ≤ 0.15)M0], and further overall survival was compared by Kaplan-Meier method. The univariate and multivariate analyses were employed for cox proportional hazards model. RESULTS: We retrospectively reviewed 5581 consecutive CRC patients with, and 2861 eligible patients were enrolled for further analysis. The optimal cut-off value of P-LNR in our study was 0.15. There was no significant difference in OS (91.36 vs. 93.74%) and DFS (87.65 vs. 90.96%) between stage III patients with pT1-3N + (P-LNR ≤ 0.15)M0 and those with pT1-3N0M0. Further analysis demonstrated that CRC patients with pT1-3N + (P-LNR ≤ 0.15)M0 were less likely to benefit from 8 cycles of CAPOX or FOLFOX chemotherapy and suffered fewer adverse events from declining chemotherapy. Comparing with 0-4 cycles versus 8 cycles, the overall survival rates were 91.35 versus 90.19% (P = 0.79), and with a DFS of 87.50 versus 88.24% (P = 0.49), the duration of adjuvant chemotherapy was not an independent risk factor for patients with pT1-3N + (P-LNR ≤ 0.15)M0 (HR: 0.70, 95% CI 0.90-1.30, P = 0.42). CONCLUSION: The concept of P-LNR we proposed might have a high clinical application value and accurately enable clinicians to screen out specific CRC patients who decline or prefer limited chemotherapy. TRIAL REGISTRY: The clinical trial registration number: ChiCTR2300076883.

Study of the Prediction of Vibrations in Soft Soil Foundations Based on Field Tests.

To explore the prediction of vibrations in soft soil foundations, in light of the construction of laboratories with microvibration requirements on soft soil foundations which are subject to the limitations of urban land planning, field testing was conducted, and the soil surface vibration responses were recorded at different distances from a road under various highway traffic loads. By analyzing the data which summarize the characteristics of soft soil foundations, it is clarified that the vibration response of soft soil foundations mainly occurs at low frequencies, and the vibration response under road traffic loads is prone to resonance at the natural frequency of soft soil foundations. Subsequently, a new vibration prediction method based on the vibration transmission ratio is proposed, and its effectiveness and accuracy based on transmissibility are verified. This research study provides a reference for laboratories constructed on soft soil and for surrounding traffic planning.

Orchestrating apoptosis and ferroptosis through enhanced sonodynamic therapy using amorphous UIO-66-CoOx.

The development of efficient and multifunctional sonosensitizers is crucial for enhancing the efficacy of sonodynamic therapy (SDT). Herein, we have successfully constructed a CoOx-loaded amorphous metal-organic framework (MOF) UIO-66 (A-UIO-66-CoOx) sonosensitizer with excellent catalase (CAT)- and glutathione-oxidase (GSH-OXD)-like activities. The A-UIO-66-CoOx exhibits a 2.6-fold increase in singlet oxygen (1O2) generation under ultrasound (US) exposure compared to crystalline UIO-66 sonosensitizer, which is attributed to its superior charge transfer efficiency and consistent oxygen (O2) supply. Additionally, the A-UIO-66-CoOx composite reduces the expression of glutathione peroxidase (GPX4) by depleting glutathione (GSH) through Co3+ and Co2+ valence changes. The high levels of highly cytotoxic 1O2 and deactivation of GPX4 can lead to lethal lipid peroxidation, resulting in concurrent apoptosis and ferroptosis. Both in vitro and vivo tumor models comprehensively confirmed the enhanced SDT antitumor effect using A-UIO-66-CoOx sonosensitizer. Overall, this study emphasizes the possibility of utilizing amorphization engineering to improve the effectiveness of MOFs-based sonosensitizers for combined cancer therapies.

Yin Yang 1 expression predicts a favourable survival in diffuse large B-cell lymphoma.

Aims: Yin Yang 1 (YY1) is a multifunctional transcription factor that plays an important role in tumour development and progression, while its clinical significance in diffuse large B-cell lymphoma (DLBCL) remains largely unexplored. This study aimed to investigate the expression and clinical implications of YY1 in DLBCL. Methods: YY1 expression in 198 cases of DLBCL was determined using immunohistochemistry. The correlation between YY1 expression and clinicopathological parameters as well as the overall survival (OS) and progression-free survival (PFS) of patients was analyzed. Results: YY1 protein expression was observed in 121 out of 198 (61.1 %) DLBCL cases. YY1 expression was significantly more frequent in cases of the GCB subgroup than in the non-GCB subgroup (P = 0.005). YY1 was positively correlated with the expression of MUM1, BCL6, pAKT and MYC/BCL2 but was negatively associated with the expression of CXCR4. No significant relationships were identified between YY1 and clinical characteristics, including age, sex, stage, localization, and B symptoms. Univariate analysis showed that the OS (P = 0.003) and PFS (P = 0.005) of patients in the YY1-negative group were significantly worse than those in the YY1-positive group. Multivariate analysis indicated that negative YY1 was a risk factor for inferior OS (P < 0.001) and PFS (P = 0.017) independent of the international prognostic index (IPI) score, treatment and Ann Arbor stage. Furthermore, YY1 is more powerful for stratifying DLBCL patients into different risk groups when combined with MYC/BCL2 double-expression (DE) status. Conclusions: YY1 was frequently expressed in DLBCL, especially in those of GCB phenotype and with MYC/BCL2-DE. As an independent prognostic factor, YY1 expression could predict a favourable outcome in DLBCL. In addition, a complex regulatory mechanism might be involved in the interactions between YY1 and MYC, pAKT as well as CXCR4 in DLBCL, which warrants further investigation.

PD-L1 expression guidance on sintilimab versus pembrolizumab with or without platinum-doublet chemotherapy in untreated patients with advanced non-small cell lung cancer (CTONG1901): A phase 2, randomized, controlled trial.

No direct comparison has been performed between different programmed cell death-1 (PD-1) inhibitors for first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). The feasibility of using PD-L1-expression-guided immunotherapy remains unknown. In this open-label, phase 2 study (NCT04252365), patients with advanced NSCLC without EGFR or ALK alterations were randomized (1:1) to receive sintilimab or pembrolizumab monotherapy (PD-L1 expression ≥ 50%), or sintilimab or pembrolizumab plus platinum-based chemotherapy (PD-L1 expression < 50%). The sample size was calculated by optimal two-stage design. The primary endpoint was the objective response rate (ORR). The study included 71 patients (sintilimab arms, n = 35; pembrolizumab arms, n = 36) and met its primary endpoint, with a confirmed ORR of 51.4% (18/35) in the sintilimab arms. The confirmed ORR (95% confidence interval) was 46.2% (19.2%, 74.9%) and 42.9% (17.7%, 71.1%) for patients treated with sintilimab and pembrolizumab monotherapy; and 54.5% (32.2%, 75.6%) and 45.4% (24.4%, 67.8%) for those treated with sintilimab- and pembrolizumab-based combination therapies. The median progression-free survival was 6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination therapies. The median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination therapies. Treatment-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase III studies. However, the incidence of rash was higher with sintilimab than pembrolizumab monotherapy. This is the first prospective phase 2 study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced NSCLC. Sintilimab was efficacious and well-tolerated irrespective of PD-L1 expression level in patients with advanced NSCLC and had similar efficacy and safety to pembrolizumab.

Integrated Diffusion Tensor Imaging and Renal Parenchymal Volume for Early Detection and Grading of Split Renal Functional Impairment in Lupus Nephritis.

RATIONALE AND OBJECTIVES: To investigate the effectiveness of combining split diffusion tensor imaging (DTI) measurements with split renal parenchymal volume (RPV) for assessing split renal functional impairment in patients with lupus nephritis (LN). MATERIALS AND METHODS: Seventy-four participants [48 LN patients and 26 healthy volunteers (HV)] were included in the study. All participant underwent conventional MR and DTI (b = 0, 400, and 600 s/mm2) examinations using a 3.0 T MRI scanner to determine the split renal DTI measurements and split RPV. In LN patients, renography glomerular filtration rate (rGFR) was measured using 99mTc-DTPA scintigraphy based on Gates' method, serving as the reference standard to categorize all split kidneys of LN patients into LN with mild impairment (LNm, n = 65 kidneys) and LN with moderate to severe (LNms, n = 31 kidneys) groups according to the threshold of 30 ml/min in spilt rGFR. All statistical analyses were performed using SPSS 25.0 and MedCalc 20.0 software packages. RESULTS: Only split medullary fractional anisotropy (FA) and the product of split medullary FA and RPV could distinguish pairwise subgroups among the HV and each LN subgroup (all p < 0.05). ROC curve analysis demonstrated that split medullary FA (AUC = 0.866) significantly outperformed other parameters in differentiating HV from LNm groups, while the product of split medullary FA and split RPV was superior in distinguishing LNm and LNms groups (AUC = 0.793) than other parameters. The combination of split medullary FA and split RPV showed best correlation with split rGFR (r = 0.534, p < 0.001). CONCLUSION: Split medullary FA, and its combination with split RPV, are valuable biomarkers for detecting early functional changes in renal alterations and predicting disease progression in patients with LN.

2D quasi-layered material with domino structure.

Interlayer coupling strength dichotomizes two-dimensional (2D) materials into layered and non-layered types. Traditionally, they can be regarded as atomic layers intrinsically linked via van der Waals (vdW) forces or covalent bonds, oriented orthogonally to their growth plane. In our work, we report a material system that differentiates from layered and non-layered materials, termed quasi-layered domino-structured (QLDS) materials, effectively bridging the gap between these two typical categories. Considering the skewed structure, the force orthogonal to the 2D QLDS-GaTe growth plane constitutes a synergistic blend of vdW forces and covalent bonds, with neither of them being perpendicular to the 2D growth plane. This unique amalgamation results in a force that surpasses that in layered materials, yet is weaker than that in non-layered materials. Therefore, the lattice constant contraction along this unique orientation can be as much as 7.7%, tantalizingly close to the theoretical prediction of 10.8%. Meanwhile, this feature endows remarkable anisotropy, second harmonic generation enhancement with a staggering susceptibility of 394.3 pm V-1. These findings endow further applications arranged in nonlinear optics, sensors, and catalysis.

Metal-organic framework boosts heterogeneous electron donor-acceptor catalysis.

Metal-organic framework (MOF) is a class of porous materials providing an excellent platform for engineering heterogeneous catalysis. We herein report the design of MOF Zr-PZDB consisting of Zr6-clusters and PZDB (PZDB = 4,4'-(phenazine-5,10-diyl)dibenzoate) linkers, which served as the heterogeneous donor catalyst for enhanced electron donor-acceptor (EDA) photoactivation. The high local concentration of dihydrophenazine active centers in Zr-PZDB can promote the EDA interaction, therefore resulting in superior catalytic performance over homogeneous counterparts. The crowded environment of Zr-PZDB can protect the dihydrophenazine active center from being attacked by radical species. Zr-PZDB efficiently catalyzes the Minisci-type reaction of N-heterocycles with a series of C-H coupling partners, including ethers, alcohols, non-activated alkanes, amides, and aldehydes. Zr-PZDB also enables the coupling reaction of aryl sulfonium salts with heterocycles. The catalytic activity of Zr-PZDB extends to late-stage functionalization of bioactive and drug molecules, including Nikethamide, Admiral, and Myristyl Nicotinate. Systematical spectroscopy study and analysis support the EDA interaction between Zr-PZDB and pyridinium salt or aryl sulfonium salt, respectively. Photoactivation of the MOF-based EDA adduct triggers an intra-complex single electron transfer from donor to acceptor, giving open-shell radical species for cross-coupling reactions. This research represents the first example of MOF-enabled heterogeneous EDA photoactivation.

The value of ICG-guided left colon vascular variation and anatomical rules for the radical resection of proctosigmoid colon cancer.

Objective: During laparoscopic radical resection for proctosigmoid colon cancer (PCC), surgeons could inadvertently damage the arteries when following the operation path.This study investigated the variations in left colon blood vessels in order to guide the scientific protection of the marginal artery (MA) during laparoscopic surgery for PCC. Methods: Data from seven patients who underwent inferior mesenteric artery (IMA) angiography were included as imaging references to preliminarily explore the vascular structure and variation in the left colon. The clinical video data of 183 PCC patients were retrospectively analyzed to observe intraoperative MA injury. Meanwhile, a prospective cohort of 96 patients with the same disease underwent intraoperative indocyanine green (ICG) fluorescence imaging of the peripheral sigmoid artery network, the variation of marginal arteries was summarized, and the distance between vessels and the bowel was measured at different levels. Patients were divided into 'ICG group' and 'non-ICG group' according to whether ICG guidance was performed, and perioperative conditions were compared between the two groups. Taking the integrity of lymph node dissection into consideration, 18 patients underwent carbon nanonode tracing. This study was conducted under the standard consent and ethical approval of the Ethics Committee of our center. Results: 7 patients with IMA angiography shared some vascular structures, defined as 'Dangerous Triangle' and 'Secure Window'. Through intraoperative observation, the primary arch was typically located 4.2 (2.3-6.0) cm away from the intestinal canal, and 5.21% (5/96) patients had poor anastomosis at the primary arch. Moreover, secondary vascular arches (6.4 (4.6-10.0) cm from the intestinal wall) were observed in 38.54% of patients. MA injury was identified in 2 of 183 cases, and the ischemic bowel was timely dissected, whereas no such injury occurred during ICG fluorescenceguided surgery. Guided by carbon nanoparticles, the integrity of lymph node dissection can be maintained while preserving the secondary arch in all patients. Conclusions: This study demonstrated the benefits of ICG guidance in protecting the intestinal blood supply in laparoscopic PCC surgery. By enhancing the understanding of primary and secondary vascular arches, secure windows, and dangerous triangles, surgeons can safely optimize the surgical path during surgery.

Stereoselective Unsymmetrical 1,1-Diborylation of Alkynes with a Neutral sp2 -sp3 Diboron Reagent.

The incorporation of two distinct boryl groups at the same carbon center in organic molecules has attracted growing research interest due to its potential for facilitating controlled, precise synthesis through stepwise dual carbon-boron bond transformations. Here we report a method to access unsymmetrical 1,1-diborylalkene (UDBA) stereoselectively via the reaction of readily available alkynes with a neutral sp2 -sp3 diboron reagent (NHC)BH2 -Bpin (NHC=N-heterocyclic carbene). Attributing to the chemically easily distinguishable nature of the sp2 and sp3 boryl moieties, controllable stepwise derivatization of the resultant UDBAs is realized. This process leads to various multifunctionalized olefins and organoborons, such as acylboranes, which are difficult to prepare by other methods.

Perilipin 1 Deficiency Prompts Lipolysis in Lipid Droplets and Aggravates the Pathogenesis of Persistent Immune Activation in Drosophila.

Lipid droplets (LDs) are highly dynamic intracellular organelles, which are involved in lots of biological processes. However, the dynamic morphogenesis and functions of intracellular LDs during persistent innate immune responses remain obscure. In this study, we induce long-term systemic immune activation in Drosophila through genetic manipulation. Then, the dynamic pattern of LDs is traced in the Drosophila fat body. We find that deficiency of Plin1, a key regulator of LDs' reconfiguration, blocks LDs minimization at the initial stage of immune hyperactivation but enhances LDs breakdown at the later stage of sustained immune activation via recruiting the lipase Brummer (Bmm, homologous to human ATGL). The high wasting in LDs shortens the lifespan of flies with high-energy-cost immune hyperactivation. Therefore, these results suggest a critical function of LDs during long-term immune activation and provide a potential treatment for the resolution of persistent inflammation.

The Mechanisms of Resistin-Like Molecule-ß-Mediated Airway Inflammation in Chronic Obstructive Pulmonary Disease via Autophagy.

Background: The role of irreversible airway inflammatory damage in chronic obstructive pulmonary disease (COPD) progression is evident. Autophagy is an essential process in the cellular material metabolic cycle, and a family of resistant vegetative molecules may be involved in the COPD autophagic process. In this study, we investigated the mechanism of resistin-like molecule ß (RELMß) in COPD smoking-induced autophagy. Methods: Firstly, the expression differences of RELMß and autophagy markers between COPD and control groups were analyzed in the Gene Expression Omnibus (GEO) datasets and clinical specimens. Secondly, in vitro and in vivo experiments were conducted using immunoblotting, immunofluorescence, immunohistochemistry, and other methods to investigate the mechanism by which RELMß promotes airway inflammation through autophagy in a cigarette smoke extract-induced 16HBE cell inflammation model and a cigarette smoke-induced COPD-like mouse model. In addition, immunoprecipitation was used to analyze the binding of RELMß to the membrane protein TLR4. Results: The expression of RELMß and autophagy genes p62 and LC3B in lung tissue of COPD patients was significantly increased. RELMß can mediate the activation of autophagy in 16HBE cells, and through autophagy, it increases the expression of inflammatory cytokines in a cigarette smoke extract-induced 16HBE cell inflammation model. RELMß promotes cigarette smoke-induced COPD-like mouse airway inflammation through autophagy, and RELMß can mediate signal transduction through the cell membrane receptor TLR4. Conclusion: The RELMß binds to TLR4 to encourage signal transduction and that RELMß can promote inflammation in smoky COPD lungs through autophagy.

Identification of ARF transcription factor gene family and its defense responses to bacterial infection and salicylic acid treatment in sugarcane.

Auxin response factor (ARF) is a critical regulator in the auxin signaling pathway, involved in a variety of plant biological processes. Here, gene members of 24 SpapARFs and 39 SpnpARFs were identified in two genomes of Saccharum spontaneum clones AP85-441 and Np-X, respectively. Phylogenetic analysis showed that all ARF genes were clustered into four clades, which is identical to those ARF genes in maize (Zea mays) and sorghum (Sorghum bicolor). The gene structure and domain composition of this ARF family are conserved to a large degree across plant species. The SpapARF and SpnpARF genes were unevenly distributed on chromosomes 1-8 and 1-10 in the two genomes of AP85-441 and Np-X, respectively. Segmental duplication events may also contribute to this gene family expansion in S. spontaneum. The post-transcriptional regulation of ARF genes likely involves sugarcane against various stressors through a miRNA-medicated pathway. Expression levels of six representative ShARF genes were analyzed by qRT-PCR assays on two sugarcane cultivars [LCP85-384 (resistant to leaf scald) and ROC20 (susceptible to leaf scald)] triggered by Acidovorax avenae subsp. avenae (Aaa) and Xanthomonas albilineans (Xa) infections and salicylic acid (SA) treatment. ShARF04 functioned as a positive regulator under Xa and Aaa stress, whereas it was a negative regulator under SA treatment. ShARF07/17 genes played positive roles against both pathogenic bacteria and SA stresses. Additionally, ShARF22 was negatively modulated by Xa and Aaa stimuli in both cultivars, particularly LCP85-384. These findings imply that sugarcane ARFs exhibit functional redundancy and divergence against stressful conditions. This work lays the foundation for further research on ARF gene functions in sugarcane against diverse environmental stressors.

Long-Term Survival and Induction of Operational Tolerance to Murine Islet Allografts by Co-Transplanting Cyclosporine A Microparticles and CTLA4-Ig.

One strategy to prevent islet rejection is to create a favorable immune-protective local environment at the transplant site. Herein, we utilize localized cyclosporine A (CsA) delivery to islet grafts via poly(lactic-co-glycolic acid) (PLGA) microparticles to attenuate allograft rejection. CsA-eluting PLGA microparticles were prepared using a single emulsion (oil-in-water) solvent evaporation technique. CsA microparticles alone significantly delayed islet allograft rejection compared to islets alone (p < 0.05). Over 50% (6/11) of recipients receiving CsA microparticles and short-term cytotoxic T lymphocyte-associated antigen 4-Ig (CTLA4-Ig) therapy displayed prolonged allograft survival for 214 days, compared to 25% (2/8) receiving CTLA4-Ig alone. CsA microparticles alone and CsA microparticles + CTLA4-Ig islet allografts exhibited reduced T-cell (CD4+ and CD8+ cells, p < 0.001) and macrophage (CD68+ cells, p < 0.001) infiltration compared to islets alone. We observed the reduced mRNA expression of proinflammatory cytokines (IL-6, IL-10, INF-γ, and TNF-α; p < 0.05) and chemokines (CCL2, CCL5, CCL22, and CXCL10; p < 0.05) in CsA microparticles + CTLA4-Ig allografts compared to islets alone. Long-term islet allografts contained insulin+ and intra-graft FoxP3+ T regulatory cells. The rapid rejection of third-party skin grafts (C3H) in islet allograft recipients suggests that CsA microparticles + CTLA4-Ig therapy induced operational tolerance. This study demonstrates that localized CsA drug delivery plus short-course systemic immunosuppression promotes an immune protective transplant niche for allogeneic islets.

First-line pyrotinib in advanced HER2-mutant non-small-cell lung cancer: a patient-centric phase 2 trial.

To explore targeted treatment options in patients with non-small-cell lung cancer (NSCLC) with rare genetic mutations in the context of a patient-centric clinical trial, we initiated, in parallel, a phase 2 adaptive umbrella trial consisting of a criteria-fulfilled (CF) cohort and a compassionate use (CU) cohort under expanded eligibility criteria, and a prospective real-world study (RWS). Here, we present efficacy and safety data from 48 patients with treatment-naive, advanced HER2-mutant NSCLC treated with the pan-HER receptor tyrosine kinase inhibitor pyrotinib (CF and CU cohorts) or physician's therapy of choice (RWS cohort). In the phase 2 trial CF cohort (n = 28), the primary endpoint was reached with an objective response rate of 35.7% after pyrotinib treatment. Secondary endpoints included disease control rate (89.3%), median progression-free survival (PFS) (7.3 months), median overall survival (OS) (14.3 months) and toxicity, which was acceptable, with grade 3 or 4 treatment-related adverse events occurring in three patients (10.7%). The phase 2 trial CU cohort (n = 12) showed an objective response rate of 16.7%, disease control rate of 83.4%, median PFS of 4.7 months and median OS of 14.2 months after pyrotinib treatment. The RWS cohort (n = 8) had no responses to physician's therapy of choice, while median PFS and OS were 3.0 and 12.2 months, respectively. Phase 2 umbrella trial, clinicaltrials.gov identifier: NCT03574402 . RWS, clinicaltrials.gov identifier: NCT03605602 .

The Power of Positive Reporting: Examining China's Anti-Epidemic National Image in Mainstream Media.

Covid-19 out broke gave an extreme impact to the globe, imposing a challenge to health publicly and causing social interruptions. As a result, the role of mainstream media in promoting anti-epidemic measures and disseminating national images has become increasingly important. In this study, we examine the anti-epidemic reports in 2020 from three types of international news sources, identifying 566 samples for content and text analysis. Through our analysis, we found that each component of the anti-epidemic report has a clear focus, and that these reports presented China's national image of anti-epidemic in four dimensions. Notably, the European version of People's Daily exhibited a positive reporting tendency, accounting for 86% of the total, with only 8% of reports being negative. This indicates a relatively comprehensive national image construction and communication strategy amid the COVID-19 pandemic. Overall, our research reveals the important role of media in shaping a nation's image during a global crisis. The positive reporting tendency of the European version of People's Daily reflects an effective strategy for promoting a positive national image, thereby dispelling misunderstandings and prejudices towards China's anti-epidemic measures. Our findings provide inspiration for the dissemination of national images in times of crisis, highlighting the importance of comprehensive and well-coordinated communication strategies to promote a positive image.