Influence of extreme 2022 heatwave on megacities' anthropogenic CO2 emissions in lower-middle reaches of the Yangtze River.

An unprecedented heatwave hit the Yangtze River Basin (YRB) in August 2022. We analyzed changes of anthropogenic CO2 emissions in 8 megacities over lower-middle reaches of the YRB, using a near-real-time gridded daily CO2 emissions dataset. We suggest that the predominant sources of CO2 emissions in these 8 megacities are from the power and industrial sectors. In comparison to the average emissions for August in 2020 and 2021, the heatwave event led to a total increase in power sector emissions of approximately 2.70 Mt CO2, potentially due to the increase in urban cooling demand. Suzhou experienced the largest increase, with a rise of 1.12 Mt CO2 (12.88 %). Importantly, we observed that changes in daily power emissions exhibited strong linear relationships with temperatures during the heatwave, albeit varying sensitivities across different megacities (with an average of 0.0076 ± 0.0075 Mt d-1 °C-1). Conversely, we find that industrial emissions decreased by a total of 8.45 Mt CO2, with Shanghai seeing the largest decrease of 4.71 Mt CO2, while Hangzhou experienced the largest relative decrease (-21.22 %). It is noteworthy that the majority of megacities rebounded in industrial emissions following the conclusion of the heatwave. We convincingly suggest a tight linkage between the reductions in industrial emissions and China's policy to ensure household power supply. Overall, the reduction in industrial emissions offset the increase in power sector emissions, resulting in weaker emissions for majority of megacities during the heatwave. Despite remaining uncertainties in the emissions data, our study may offer valuable insights into the complexities of anthropogenic CO2 emissions in megacities amidst frequent summer heatwaves intensified by greenhouse warming.

Two novel compounds inhibit Flavivirus infection in vitro and in vivo by targeting lipid metabolism.

Flavivirus infection capitalizes on cellular lipid metabolism to remodel the cellular intima, creating a specialized lipid environment conducive to viral replication, assembly, and release. The Japanese encephalitis virus (JEV), a member of the Flavivirus genus, is responsible for significant morbidity and mortality in both humans and animals. Currently, there are no effective antiviral drugs available to combat JEV infection. In this study, we embarked on a quest to identify anti-JEV compounds within a lipid compound library. Our research led to the discovery of two novel compounds, isobavachalcone (IBC) and corosolic acid (CA), which exhibit dose-dependent inhibition of JEV proliferation. Time-of-addition assays indicated that IBC and CA predominantly target the late stage of the viral replication cycle. Mechanistically, JEV nonstructural proteins 1 and 2A (NS1 and NS2A) impede 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation by obstructing the liver kinase B1 (LKB1)-AMPK interaction, resulting in decreased p-AMPK expression and a consequent upsurge in lipid synthesis. In contrast, IBC and CA may stimulate AMPK by binding to its active allosteric site, thereby inhibiting lipid synthesis essential for JEV replication and ultimately curtailing viral infection. Most importantly, in vivo experiments demonstrated that IBC and CA protected mice from JEV-induced mortality, significantly reducing viral loads in the brain and mitigating histopathological alterations. Overall, IBC and CA demonstrate significant potential as effective anti-JEV agents by precisely targeting AMPK-associated signaling pathways. These findings open new therapeutic avenues for addressing infections caused by Flaviviruses. IMPORTANCE: This study is the inaugural utilization of a lipid compound library in antiviral drug screening. Two lipid compounds, isobavachalcone (IBC) and corosolic acid (CA), emerged from the screening, exhibiting substantial inhibitory effects on the Japanese encephalitis virus (JEV) proliferation in vitro. In vivo experiments underscored their efficacy, with IBC and CA reducing viral loads in the brain and mitigating JEV-induced histopathological changes, effectively shielding mice from fatal JEV infection. Intriguingly, IBC and CA may activate 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) by binding to its active site, curtailing the synthesis of lipid substances, and thus suppressing JEV proliferation. This indicates AMPK as a potential antiviral target. Remarkably, IBC and CA demonstrated suppression of multiple viruses, including Flaviviruses (JEV and Zika virus), porcine herpesvirus (pseudorabies virus), and coronaviruses (porcine deltacoronavirus and porcine epidemic diarrhea virus), suggesting their potential as broad-spectrum antiviral agents. These findings shed new light on the potential applications of these compounds in antiviral research.

Current Trial Report: A Multicenter Phase I/Ib study of Capmatinib Plus Trametinib in Patients With Metastatic Nonsmall Cell Lung Center Harboring MET Exon 14 Skipping Mutations and Other MET-Alterations.

INTRODUCTION: MET tyrosine kinase inhibitor (TKI) therapy is associated with improved outcomes in patients with nonsmall cell lung cancer (NSCLC) harboring a MET alteration, including MET exon 14 (METex14) skipping mutation, MET amplification, or MET fusion. However, primary or acquired resistance to TKI therapy ultimately develops. In preclinical models, hyperactivation of MAPK signaling was shown to promote resistance to MET TKI; resistance was overcome by co-treatment with a MET inhibitor and a MEK inhibitor. This phase I/Ib study offers a potential combination strategy simultaneously targeting MET (with capmatinib) and MEK signaling (with trametinib) to overcome resistance to MET inhibitor monotherapy in METex14 NSCLC. METHODS: In the dose escalation phase, a minimum of 6 and maximum of 18 patients will be enrolled using a conventional 3+3 design with the primary endpoint of identifying a recommended phase 2 dose (RP2D) of capmatinib in combination with trametinib. Once the RP2D is identified, patients will continue to enroll in a dose expansion phase to a total of 15 patients. The primary endpoint of the dose expansion phase is to further characterize the safety profile of the combination. CONCLUSION: This phase I/Ib clinical trial will assess the safety and efficacy of combination capmatinib and trametinib in NSCLC patients whose tumors harbor METex14 skipping mutations, MET amplification, or MET fusion and had developed progressive disease on single agent MET inhibitor therapy.

Quantile regressions as a tool to evaluate how an exposure shifts and reshapes the outcome distribution: A primer for epidemiologists.

Quantifying how an exposure affects the entire outcome distribution is often important, e.g., for outcomes such as blood pressure which have non-linear effects on long-term morbidity and mortality. Quantile regressions offer a powerful way of estimating an exposure's relationship with the outcome distribution but remain underused in epidemiology. We introduce quantile regressions with a focus on distinguishing estimators for quantiles of the conditional and unconditional outcome distributions. We also present an empirical example in which we fit mean and quantile regressions to investigate educational attainment's association with later-life systolic blood pressure (SBP). We use data on 8,875 US-born respondents aged 50+ years from the US Health and Retirement Study. More education was negatively associated with mean SBP. Conditional and unconditional quantile regressions both suggested a negative association between education and SBP at all levels of SBP, but the absolute magnitudes of these associations were higher at higher SBP quantiles relative to lower quantiles. In addition to showing that educational attainment shifted the SBP distribution left-wards, quantile regression results revealed that education may have reshaped the SBP distribution through larger protective associations in the right tail, thus benefiting those at highest risk of cardiovascular diseases.

Structural Design and Performance of Cut-Resistant Fabrics with Concave-Convex Arrays.

As the risk of social security increases, it is crucial to develop flexible protective materials that combine flexibility with high protective performance. Ultra-high-molecular-weight polyethylene (UHMWPE) was selected as the raw material, and four types of flat-knitting cut-resistant fabrics were ultimately designed and prepared from a three-dimensional longitudinal dimension and concave-convex array structure based on rib knitting. A series of experiments must be conducted on fabrics in order to study the law of protection performance of different structural fabrics. They were thus subjected to comprehensive evaluation and theoretical analysis of cut resistance. The results demonstrate that the four structural fabrics exhibited resilience in abrasion tests, withstanding over 100,000 cycles without failure. A weighting algorithm was employed to determine the comprehensive cutting resistance of the S1, S2, S3, and S4 structural fabrics, resulting in values of 1939.9 gf, 2298.6 gf, 2577.1 gf, and 2822.2 gf, respectively. Therefore, S1 reached class A4, which is sufficient to address a medium cut hazard. Similarly, S2, S3, and S4 reached class A5, which is adequate to address a high cut hazard. The obtained fitting equation, with uniform yarn fineness T as the dependent variable, demonstrates that the cut resistance improved as the concave-convex density level increased.

Association between calcification and risk stratification in gastric gastrointestinal stromal tumors.

BACKGROUND: Risk assessment of gastric gastrointestinal stromal tumors (GISTs), particularly those with a diameter ≤ 5 cm, remains a clinical challenge. Previous research has primarily focused on tumor size, ulceration, necrosis, and enhancement patterns, with less emphasis on the role of tumor calcification, which remains controversial regarding its correlation with malignancy risk. OBJECTIVE: This study aims to explore the characteristics of calcification in gastric GISTs and its correlation with risk stratification as defined by the National Institutes of Health (NIH), to improve preoperative risk assessment for gastric GISTs ≤ 5 cm. METHODS: A retrospective analysis of 385 pathologically confirmed gastric GIST patients, including 178 with small gastric GISTs (< 2 cm), was conducted. Tumors were categorized into low-risk (very low / low) and high-risk (intermediate / high) groups based on NIH criteria. Variables such as age, gender, tumor long-axis diameter, calcification rates, calcification size, the number and distribution of calcification, calcification to tumor long-axis diameter ratio were analyzed. Logistic regression was used to identify independent predictors of malignancy for gastric GISTs, with predictive values assessed via receiver operating characteristic (ROC) curves. RESULTS: Significant differences were found between high-risk and low-risk groups in treatment methods, tumor long-axis diameter, the ratio of calcification to tumor long-axis, and calcification distribution (P < 0.05). Calcification rates varied across risk categories, with 23.6% in very low-risk, 31.6% in low-risk, 9.8% in intermediate-risk, and 31.7% in high-risk categories (P < 0.05). In GISTs ≤ 5 cm, both tumor long-axis diameter (OR = 3.07, 95% CI: 2.29-4.10) and calcification (OR = 0.36, 95% CI: 0.13-0.97) were independent predictors of malignancy risk (both P < 0.05). ROC curve analysis yielded areas of 0.849 for tumor long-axis diameter, 0.578 for calcification, and 0.862 for their combination. CONCLUSION: The study indicates lower calcification rates in intermediate-risk gastric GISTs and higher rates in other risk categories. Additionally, tumors of different sizes exhibit two distinct calcification patterns, suggesting possible differing mechanisms of calcification in tumors. Calcification in gastric GISTs ≤ 5 cm acts as a protective factor against higher malignancy risk, and when combined with tumor long-axis diameter, significantly enhances predictive accuracy over long-axis diameter alone.

The neonatal Fc receptor (FcRn) is a pan-arterivirus receptor.

Arteriviruses infect a variety of mammalian hosts, but the receptors used by these viruses to enter cells are poorly understood. We identified the neonatal Fc receptor (FcRn) as an important pro-viral host factor via comparative genome-wide CRISPR-knockout screens with multiple arteriviruses. Using a panel of cell lines and divergent arteriviruses, we demonstrate that FcRn is required for the entry step of arterivirus infection and serves as a molecular barrier to arterivirus cross-species infection. We also show that FcRn synergizes with another known arterivirus entry factor, CD163, to mediate arterivirus entry. Overexpression of FcRn and CD163 sensitizes non-permissive cells to infection and enables the culture of fastidious arteriviruses. Treatment of multiple cell lines with a pre-clinical anti-FcRn monoclonal antibody blocked infection and rescued cells from arterivirus-induced death. Altogether, this study identifies FcRn as a novel pan-arterivirus receptor, with implications for arterivirus emergence, cross-species infection, and host-directed pan-arterivirus countermeasure development.

Open vs. closed reduction with pinning for displaced Rockwood and Wilkins' type C thumb metacarpal base fractures in children.

Background: The treatment of severely displaced Rockwood and Wilkins' type C (RWC) thumb metacarpal basal fractures remains controversial in children. This retrospective study aimed to compare the efficacy of two treatment methods, open vs. closed reduction with pinning of such injuries. Methods: This study included 30 patients with open physes, 14 boys and 16 girls, who all received either closed or open reduction treatment. The primary outcomes of interest included healing time, complications, and functional results, which were evaluated using the improved Mayo score standard. The minimum follow-up period was 24 months, with a mean of 30.3 months (range 24.0-45.0 months). Statistical significant was defined as P < 0.05. Results: All fractures were healed within 7 weeks after surgery, regardless of which surgical approach was used. However, the recovery time was markedly faster in the closed group, with a mean of 4.2 weeks, than in the open group, with a mean of 4.7 weeks (P < 0.05). The operation time for closed group, taking 20 min in average, was also shorter than that for open group (P < 0.05). The total incidence of mild complications was lower for patients in the closed group than for patients in the open group (6.3% vs. 21.4%, P < 0.05). No major complications were observed in either group. In the closed group, a total of 15 patients exhibited excellent outcomes, while only one patient demonstrated good outcomes. On the other hand, in the open group, 12 patients experienced excellent outcomes, whereas two patients had good outcomes. There were no instances of osteomyelitis, refractures or nonunion, avascular necrosis (AVN), or premature physeal closure in either group. Conclusion: The data from the open group and closed group procedures for severely shifted RWC fractures in children indicate comparable prognoses and complication rates between the two groups. Obviously closed reduction, in particular, offers several advantages over open procedure, including shorter surgical duration, fewer K-wires required, and no need for open incisions. Consequently, closed reduction is the preferred method for treating such RWC fractures.

Preparation of bacterial cellulose/acrylic acid-based pH-responsive smart dressings by graft copolymerization method.

Conventional wound dressings used in trauma treatment have a single function and insufficient adaptability to the wound environment, making it difficult to meet the complex demands of the healing process. Stimuli-responsive hydrogels can respond specifically to the particular environment of the wound area and realize on-demand responsive release by loading active substances, which can effectively promote wound healing. In this paper, BC/PAA-pH responsive hydrogels (BPPRHs) were prepared by graft copolymerization of acrylic acid (AA) to the end of the molecular chain of bacterial cellulose (BC) network structure. Antibacterial pH-responsive 'smart' dressings were prepared by loading curcumin (Cur) onto the hydrogels. Surface morphology, chemical groups, crystallinity, rheological, and mechanical properties of BPPRHs were analyzed by different characterization methods. The drug release behavior under different physiological conditions and bacteriostatic properties of BPPRH-Cur dressings were also investigated. The results of structural characterization and performance studies show that the hydrogel has a three-dimensional mesh structure and can respond to wound pH in a 'smart' drug release capacity. The drug release behavior of the BPPRH-Cur dressings under different environmental conditions conformed to the logistic and Weibull kinetic models. BPPRH-Cur displayed good antimicrobial activity against common pathogens of wound infections such as E. coli, S. aureus, and P. aeruginosa by destroying the cell membrane and lysing the bacterial cells. This study lays the foundation for the development of new pharmaceutical dressings with positive health, economic and social benefits.

Patient-specific mechanical analysis of pedicle screw insertion in simulated osteoporotic spinal bone models derived from medical images.

Study Design: Biomechanical study. Purpose: To investigate the mechanical characteristics of bone models created from medical images. Overview of Literature: Recent advancements in three-dimensional (3D) printing technology have affected its application in surgery. However, a notable gap exists in the analyses of how patient's dimorphism and variations in vertebral body anatomy influence the maximum insertional torque (MIT) and pullout strength (POS) of pedicle screws (PS) in osteoporotic vertebral bone models derived from medical images. Methods: Male and female patients with computed tomography data were selected. Dimensions of the first thoracic (T1), fourth lumbar (L4), and fifth lumbar (L5) vertebrae were measured, and bone models consisting of the cancellous and cortical bones made from polyurethane foam were created. PS with diameters of 4.5 mm, 5.5 mm, and 6.5 mm were used. T1 PS were 25 mm long, and L4 and L5 PS were 40 mm long. The bone models were secured with cement, and the MIT was measured using a calibrated torque wrench. After MIT testing, the PS head was attached to the machine's crosshead. POS was then calculated at a crosshead speed of 5 mm/min until failure. Results: The L4 and L5 were notably larger in female bone models, whereas the T1 vertebra was larger in male bone models. Consequently, the MIT and POS for L4 and L5 were higher in female bone models across all PS diameters than in male bone models. Conversely, the MIT for T1 was higher in male bone models across all PS; however, no significant differences were observed in the POS values for T1 between sexes. Conclusions: The mechanical properties of the proposed bone models can vary based on the vertebral structure and size. For accurate 3D surgical and mechanical simulations in the creation of custom-made medical devices, bone models must be constructed from patientspecific medical images.

High-resolution satellite estimates of coal mine methane emissions from local to regional scales in Shanxi, China.

Coal mines are significant anthropogenic sources of methane emissions, detectable and traceable from high spatial resolution satellites. Nevertheless, estimating local or regional-scale coal mine methane emission intensities based on high-resolution satellite observations remains challenging. In this study, we devise a novel interpolation algorithm based on high-resolution satellite observations (including Gaofen5-01A/02, Ziyuan-1 02D, PRISMA, GHGSat-C1 to C5, EnMAP, and EMIT) and conduct assessments of annual mean coal mine methane emissions in Shanxi Province, China, one of the world's largest coal-producing regions, spanning the period 2019 to 2023 across various scales: point-source, local, and regional. We use high-resolution satellite observations to perform interpolation-based estimations of methane emissions from three typical coal-mining areas. This approach, known as IPLTSO (Interpolation based on Satellite Observations), provides spatially explicit maps of methane emission intensities in these areas, thereby providing a novel local-scale coal mine methane emission inventory derived from high-resolution top-down observations. For regional-scale estimation and mapping, we utilize high-resolution satellite data to complement and substitute facility-level emission inventories for interpolation (IPLTSO+GCMT, Interpolation based on Satellite Observations and Global Coal Mine Tracker). We evaluate our IPLTSO and IPLTSO+GCMT estimation with emission inventories, top-down methane emission estimates from TROPOMI observations, and TROPOMI's methane concentration enhancements. The results suggest a notable right-skewed distribution of methane emission flux rates from coal mine point sources. Our IPLTSO+GCMT estimates the annual average coal mine methane emission in Shanxi Province from 2019 to 2023 at 8.9 ± 0.5 Tg/yr, marginally surpassing top-down inversion results from TROPOMI (8.5 ± 0.6 Tg/yr in 2019 and 8.6 ± 0.6 Tg/yr in 2020). Furthermore, the spatial patterns of methane emission intensity delineated by IPLTSO+GCMT and IPLTSO closely mirror those observed in TROPOMI's methane enhancements. Our comparative assessment underscores the superior performance and substantial potential of the developed interpolation algorithm based on high-resolution satellite observations for multi-scale estimation of coal mine methane emissions.

Redox-Neutral Coupling of Allyl Alcohols with Trifluoromethyl Ketones via Synergistic Ni-Ti Bimetallic Catalysis.

A redox-neutral coupling of allyl alcohols with trifluoromethyl ketones has been developed via Ni-Ti bimetallic catalysis. This innovative method allows for the efficient synthesis of various ß-tertiary trifluoromethyl alcohol-substituted ketones with yields of up to 98%. The reaction is scalable and compatible with a wide range of substrates, including complex bioactive molecules. Mechanistic studies suggest that the rate-determining step involving ß-H elimination and the presence of the Ti-based Lewis acid, as well as a hydroxyl group on the substrates, is crucial for driving the reactivity of this transformation.

Long-Term Outcomes of Antegrade Thoracic Stent Grafting During Repair of Acute DeBakey I Dissection.

BACKGROUND: We aim to evaluate the impact of antegrade stenting of the distal arch and proximal descending aorta combined with non-total arch procedures in acute type A aortic dissection. METHODS: From 2005 to 2022, 733 non-syndromic patients presented with acute DeBakey type I aortic dissection and underwent non total arch procedure. Ninety-five patients underwent antegrade stenting and 638 did not. Propensity-score analysis was performed, and 95 optimal pairs were created. Survival was estimated using the Kaplan-Meier method and cumulative incidence of reintervention with death as a competing event was calculated and compared using Gray's method. RESULTS: Survival estimates at 10 years after propensity score matching were similar between both group 58.9% (95%CI: 46.5-74.5) versus 58.4% (95%CI: 48.3-70.6) (p=0.6) in the non-stented versus stented group respectively. Cumulative incidence of reintervention with competing risk of death at 10 years after propensity matching was 27% (95%CI: 17-37) versus 22% (95%CI: 14-32) (p=0.44). CONCLUSIONS: Antegrade TEVAR may be beneficial for remodeling and facilitating future endovascular reinterventions and reduces the occurence of reintervention for malperfusion.

Mechanism Study on the Immobilization of Cu2+/Pb2+ in Aqueous Phase by Mineral Co-Milling-Modified Biochar.

A large number of studies have shown that the modification of biochar can greatly improve its adsorption capacity. This study adopts a one-step ball milling technology without solvent medium, using sawdust biochar (600 °C) and attapulgite/diatomaceous earth to prepare MABC10%/MDBC10% (mass ratio: 10% attapulgite/diatomite +90% biochar coabrasive). Characterization experiments show that attapulgite/diatomite was successfully loaded on biochar and has more C/O functional groups and wider adsorption pore sizes. Adsorption kinetics and isotherm experiments show that the adsorption process of MABC10% and MDBC10% on Cu2+/Pb2+ was mainly multilayer chemical adsorption. The adsorption capacities of MABC10% and MDBC10% for Cu2+ were 40.85 and 65.20 mg·L-1, respectively. The adsorption amounts of Pb2+ were 82.63 and 71.32 mg·L-1, respectively. The particle diffusion model shows that the adsorption process was controlled by both the surface adsorption rate limitation and boundary layer diffusion. The higher acidity in the solution will cause part of the negative charges on the surface of attapulgite/diatomite to be neutralized, thereby hindering its adsorption of Cu2+/Pb2+. The presence of coexisting ions did not significantly affect the adsorption performance. Mechanistic studies have shown that pore diffusion, active sites provided by C/O functional groups, electrostatic interactions, and cation exchange are the main mechanisms of MABC10% adsorption of Cu2+/Pb2+. In summary, MABC10% has a significant adsorption synergistic effect compared to MBC. It was an economical and effective adsorbent, and the higher the pH value of the wastewater, the more significant the adsorption effect.

Impact of Posttreatment SPECT/CT on Patient Management During 177Lu-PSMA-617 Radiopharmaceutical Therapy.

177Lu can be imaged after administration using SPECT/CT. Most work to date has focused on using posttreatment imaging to measure normal organ and tumor dose. We aimed to assess the impact of posttreatment SPECT/CT on the management of patients undergoing 177Lu-prostate-specific membrane antigen (PSMA) radiopharmaceutical therapy (RPT). Methods: In this retrospective study, 122 patients underwent PSMA RPT with subsequent SPECT/CT 24 h after treatment. We determined a qualitative response at each cycle and reviewed patient charts to assess the impact that posttreatment SPECT/CT had on patient management. Changes in patient management were classified as changes on the basis of progression and response, and specific cycles when they occurred were noted. Miscellaneous changes in patient management were also evaluated. Results: Among the 122 consecutive patients examined, 42%-56% exhibited stable disease, whereas 19%-39% of patients exhibited response on visual assessment across treatment cycles. In total, 49% (n = 60) of patients experienced changes in management, of which 57% (n = 34) were due to progression, 40% (n = 24) were due to response, and 3% (n = 2) were due to miscellaneous changes. Changes due to disease progression were observed mostly after cycles 2 and 4. Changes due to response to RPT occurred mostly after cycles 3 and 4. Conclusion: At our center, 49% of patients experienced changes in management based on posttreatment SPECT/CT, and most of these changes occurred at cycles 2 and 4. Integrating posttreatment SPECT/CT into routine PSMA RPT protocols can aid in patient management.

Longitudinal Outcomes of Thoracic Endovascular Aortic Repair for Ruptured Thoracic Aortic Aneurysms.

OBJECTIVES: Limited data exist on long-term mortality and reintervention rates of emergent thoracic endovascular aortic repair (TEVAR) for ruptured thoracic aortic aneurysm (rTAA). This study aimed to characterize the long-term outcomes of emergent TEVAR for rTAA. METHODS: This study reviewed all TEVARs for emergent rTAA and elective intact thoracic aortic aneurysms (iTAA) from August 2005 to March 2022 at a large academic medical center. Outcomes, including overall survival and reinterventions, were considered over eight years. RESULTS: Of 321 patients, 65 received TEVAR for rTAA (34 hemodynamically stable) and 256 for iTAA. Respective mean (SD) ages were 74.4 (11.9) and 74.7 (9.1) years. Median follow-up was 5.1 years. rTAA patients had lower 30-day survival (69.2% vs 96.9%, P < .001) and higher rates of stroke, pneumonia, and prolonged ventilation (all P ≤ .01). Survival was significantly worse for rTAA at 1 year (46% vs 86%), 5 years (27% vs 48%), and 8 years (20% vs 32%; all P < .001). For patients surviving at least 90 days, the long-term survival difference narrowed to statistical insignificance. Ruptured aneurysms required more reinterventions within 30 days, but comparable long-term reintervention rates. Indications for reintervention were similar, with type I endoleak as the leading cause. Long-term survival for hemodynamically stable rTAA patients did not differ significantly from iTAA patients (49% vs 48% at 5 years). CONCLUSIONS: Short-to-medium-term outcomes are worse for ruptured aneurysms. However, long-term survival of hemodynamically stable rTAA patients and rTAA patients who survive the first 90 days are comparable to iTAA patients.

A BODIPY-Ferrocene Conjugate for the Combined Photodynamic Therapy and Chemodynamic Therapy with Improved Antitumor Efficiency.

Photodynamic therapy (PDT) can destroy tumor cells by generating singlet oxygen (1O2) under light irradiation, which is limited by the hypoxia of the neoplastic tissue. Chemodynamic therapy (CDT) can produce toxic hydroxyl radical (•OH) to eradicate tumor cells by catalytic decomposition of endogenous hydrogen peroxide (H2O2), the therapeutic effect of which is highly dependent on the concentration of H2O2. Herein, we propose a BODIPY-ferrocene conjugate with a balanced 1O2 and •OH generation capacity, which can serve as a high-efficiency antitumor agent by combining PDT and CDT. The ferrocene moieties endow the as-prepared conjugates with the ability of chemodynamic killing of tumor cells. Moreover, combined PDT/CDT therapy with improved antitumor efficiency can be realized after exposure to light irradiation. Compared with the monotherapy by PDT or CDT, the BODIPY-ferrocene conjugates can significantly increase the intracellular ROS levels of the tumor cells after light irradiation, thereby inducing the tumor cell apoptosis at low drug doses. In this way, a synergistic antitumor treatment is achieved by the combination of PDT and CDT.

B4 suppresses lymphoma progression by inhibiting fibroblast growth factor binding protein 1 through intrinsic apoptosis.

Lymphoma positions as the fifth most common cancer, in the world, reporting remarkable deaths every year. Several promising strategies to counter this disease recently include utilizing small molecules that specifically target the lymphoma cellular proteins to overwhelm its progression. FGFBP1 is a soluble intracellular protein that progresses cancer cell proliferation and is upregulated in several cancers. Therefore, inhibiting FGFBP1 could significantly slow down lymphoma progression through triggering apoptosis. Thus, in this study, a flavonoid B4, isolated from Cajanus cajan, has been investigated for its effects of B4 on lymphoma, specifically as an FGFBP1 inhibitor. B4 could selectively hinder the growth of lymphoma cells by inducing caspase-dependent intrinsic apoptosis through G1/S transition phase cell cycle arrest. RNA sequencing analysis revealed that B4 regulates the genes involved in B-cell proliferation and DNA replication by inhibiting FGFBP1 in vitro. B4 increases the survival rate of lymphoma mice. B4 also represses the growth of patient-derived primary lymphoma cells through FGFBP1 inhibition. Drug affinity responsive target stability experimentations authorize that B4 powerfully binds to FGFBP1. The overexpression of FGFBP1 raises the pharmacological sensitivity of B4, supplementing its specific action on lymphoma cells. This study pioneers the estimation of B4 as a possible anticancer agent for lymphoma treatment. These outcomes highlight its selective inhibitory effects on lymphoma cell growth by downregulating FGFBP1 expression through intrinsic apoptosis, causing mitochondrial and DNA damage, ultimately leading to the inhibition of lymphoma progression. These suggest B4 may be a novel FGFBP1 inhibitor for the lymphoma treatment.

CircCDC42-encoded CDC42-165aa regulates macrophage pyroptosis in Klebsiella pneumoniae infection through Pyrin inflammasome activation.

The circular RNA (circRNA) family is a group of endogenous non-coding RNAs (ncRNAs) that have critical functions in multiple physiological and pathological processes, including inflammation, cancer, and cardiovascular diseases. However, their roles in regulating innate immune responses remain unclear. Here, we define Cell division cycle 42 (CDC42)-165aa, a protein encoded by circRNA circCDC42, which is overexpressed in Klebsiella pneumoniae (KP)-infected alveolar macrophages. High levels of CDC42-165aa induces the hyperactivation of Pyrin inflammasomes and aggravates alveolar macrophage pyroptosis, while the inhibition of CDC42-165aa reduces lung injury in mice after KP infection by inhibiting Pyrin inflammasome-mediated pyroptosis. Overall, these results demonstrate that CDC42-165aa stimulates Pyrin inflammasome by inhibiting CDC42 GTPase activation and provides a potential clinical target for pathogenic bacterial infection in clinical practice.

Efficacy of azasetron on postoperative chronic pain after pulmonary surgery: a randomized triple-blind controlled trial.

BACKGROUND: Inhibition of 5-HT3 (5-Hydroxyl Tryptamine) receptors is known to enhance morphine analgesia in animal models. We tested the efficacy of azasetron, a 5-HT3 receptor antagonist, on postoperative chronic pain after pulmonary surgery in a randomized triple-blind controlled study. METHODS: A total of 250 patients who were scheduled to receive pulmonary surgery were randomized to patient-controlled analgesia (PCA) using 200 µg sufentanil with normal saline or 200 µg sufentanil with 20 mg azasetron. The numerical rating scale of pain (NRS) was recorded at baseline, postoperative day (POD) 1, 2, 3, 90, and 180. Negative binomial regression was used to identify associated factors for postoperative NRS six months after surgery. RESULTS: The results showed that azasetron did not affect the primary outcomes: the incidence of postoperative chronic pain on POD90 and 180. However, azasetron decreased postoperative NRS at rest and activity on POD1, 2, and 3. Furthermore, azasetron decreased postoperative nausea and vomiting on POD1 and 2. Univariate and multivariate negative binomial regression analysis identified preoperative pain, smoking, drinking and open surgery are risk factors of chronic pain six months after surgery. CONCLUSIONS: Azasetron did not affect the incidence of chronic pain after pulmonary surgery. The presence of preoperative pain, smoking, drinking, and open surgery were found to be associated with chronic pain six months after surgery. CLINICAL TRIAL REGISTRATION: The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200060139), 20/05/2022; the site url is https://www.chictr.org.cn/ .