Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

Safety and short-term outcomes of esophagectomy after neoadjuvant immunotherapy combined with chemotherapy or chemoradiotherapy for locally advanced esophageal squamous cell cancer: analysis of two phase-II clinical trials.

Background: Preoperative chemotherapy (CT) or chemoradiotherapy (CRT) show survival benefits in patients with locally advanced esophageal squamous cell carcinoma (ESCC); however, ESCC patients still have a dismal prognosis. We conducted two phase-II, single-armed clinical trials to assess the potential benefits, efficacy, feasibility, and safety of esophagectomy after combining preoperative CT or CRT and neoadjuvant programmed cell death protein 1 (PD-1) inhibitors in the treatment of ESCC. Methods: Patients were included with histologically confirmed ESCC (clinical stage II-IVA according to the American Joint Committee on Cancer 8th staging system) from two phase-II, single-arm trials (NCT04506138 and NCT03940001). Patients underwent two doses of intravenous PD-1 inhibitor (either camrelizumab or sintilimab) every 3 weeks, combined with two cycles of either CT or CRT. The primary endpoint of the study was the safety and short-term outcomes of esophagectomy as measured by the risk of developing complications within 30 days, after the combination of preoperative PD-1 inhibitor and CT or CRT Secondary endpoint was to evaluate the pCR rates (pT0N0), primary tumor pCR rates (pT0), operation time, postoperative stay, and 30-day mortality rate between both groups. Results between both groups were compared using a multivariable log-binomial regression model to obtain the adjusted relative risk ratios (RRs). Results: Between May 2019 and June 2022, 55 patients were included. All patients completed neoadjuvant therapy. Age, sex, performance status, clinical stage, histologic subtype, procedure type, operative time, and blood loss volume were similar between the two groups. The primary tumor pCR rates were 52.9% in the nICRT group and 21.6% in the nICT group (P=0.03), while the postoperative pCR rates were 41.2% in the nICRT group and 21.6% in the nICT group (P=0.19). The minimally invasive surgery rates were 89.2% (33/37) in the nICT group and 94.1% (16/17) in the nICRT group. The risk of developing pulmonary, anastomotic, or other complications were similar between the two groups. Conclusions: Esophagectomy was safe after the addition of the PD-1 inhibitor to preoperative CT or CRT in ESCC neoadjuvant therapies. Follow-up and the exploratory endpoints, including biomarkers analyses, are ongoing.

Thoracoscopic pulmonary resection combined with real-time image-guided percutaneous ablation for multiple pulmonary nodules: a novel surgical approach and literature review.

Background: Due to the widespread use of computed tomography (CT) screening and advances in diagnostic techniques, an increasing number of patients with multiple pulmonary nodules are being detected and pathologically diagnosed as synchronous multiple primary lung cancers (sMPLC). It has become a new challenge to treat multiple pulmonary nodules and obtain a favorable prognosis while minimizing the perioperative risk for patients. The purpose of this study was to summarize the preliminary experience with a hybrid surgery combining pulmonary resection and ablation for the treatment of sMPLC and to discuss the feasibility of this novel procedure with a literature review. Methods: This is a retrospective non-randomized controlled study. From January 1, 2022 to July 1, 2023, four patients underwent hybrid surgery combining thoracoscopic pulmonary resection and percutaneous pulmonary ablation for multiple pulmonary nodules. Patients were followed up at 3, 6 and 12 months postoperatively and the last follow-up was on November 30, 2023. Clinical characteristics, perioperative outcomes, pulmonary function recovery and oncologic prognosis were recorded. Meanwhile we did a literature review of studies on hybridized pulmonary surgery for the treatment of multiple pulmonary nodules. Results: All the four patients were female, aged 52 to 70 years, and had no severe cardiopulmonary dysfunction on preoperative examination. Hybrid surgery of simultaneous pulmonary resection and ablation were performed in these patients to treat 2 to 4 pulmonary nodules, assisted by intraoperative real-time guide of C-arm X-ray machine. The operation time was from 155 to 240 minutes, and intraoperative blood loss was from 50 to 200 mL. Postoperative hospital stay was 2 to 7 days, thoracic drainage duration was 2 to 6 days, and pleural drainage volume was 300-1,770 mL. One patient presented with a bronchopleural fistula due to pulmonary ablation; the fistula was identified and sutured during thoracoscopic surgery and the patient recovered well. No postoperative 90-day complications occurred. After 3 months postoperatively, performance status scores for these patients recovered to 80 to 100. No tumor recurrence or metastasis was detected during the follow-up period. Conclusions: Hybrid procedures combining minimally invasive pulmonary resection with ablation are particularly suitable for the simultaneous treatment of sMPLC. Patients had less loss of pulmonary function, fewer perioperative complications, and favorable oncologic prognosis. Hybrid surgery is expected to be a better treatment option for patients with sMPLC.

Bioactive chitosan/polydopamine nanospheres coating on carbon fiber towards strengthening epoxy composites.

This paper initially examines the feasibility and effectiveness on interfacial adhesion of composites when grafting nanoparticle-structured polydopamine (PDA) and chitosan around carbon fiber periphery. The resulting interfacial shear strength was maximized as 92.3 MPa, delivering 50.1 % and 15.7-16.2 % gains over those of control fiber and only polydopamine nanospheres (PDANPs) or only chitosan modified fiber composites. Measuring surface morphology and thermal stability of fibers found that abundant PDANPs well adhered with the help of chitosan, highlighting nanoscale size effects and intrinsic adhesiveness of PDA. Under good wettability, rich and dense interfacial interactions (covalent and hydrogen bond, electrostatic interaction, and π conjugation) caused by PDANPs/chitosan coating provides impetus for effective stress transfer. Additionally, the stable "soft-rigid" combination of chitosan and PDANPs adds the efficiency of crack passivation. As such, it is hoped that this work could fully explore the possibility of PDA geometry in interphase engineering of fiber composites.

Floral Response to Heat: A Study of Color and Biochemical Adaptations in Purple Chrysanthemums.

Chrysanthemums are among the world's most popular cut flowers, with their color being a key ornamental feature. The formation of these colors can be influenced by high temperatures. However, the regulatory mechanisms that control the fading of chrysanthemum flower color under high-temperature stress remain unclear. This study investigates the impact of high temperatures on the color and biochemical responses of purple chrysanthemums. Four purple chrysanthemum varieties were exposed to both normal and elevated temperature conditions. High-temperature stress elicited distinct responses among the purple chrysanthemum varieties. 'Zi Feng Che' and 'Chrystal Regal' maintained color stability, whereas 'Zi Hong Tuo Gui' and 'Zi lian' exhibited significant color fading, particularly during early bloom stages. This fading was associated with decreased enzymatic activities, specifically of chalcone isomerase (CHI), dihydroflavonol 4-reductase (DFR), and anthocyanidin synthase (ANS), indicating a critical period of color development under heat stress. Additionally, the color fading of 'Zi Lian' was closely related to the increased activity of the peroxidase (POD) and polyphenol oxidase (PPO). Conversely, a reduction in ß-glucosidase (ßG) activity may contribute significantly to the color steadfastness of 'Zi Feng Che'. The genes Cse_sc027584.1_g010.1 (PPO) and Cse_sc031727.1_g010.1 (POD) might contribute to the degradation of anthocyanins in the petals of 'Zi Hong Tuo Gui' and 'Zi Lian' under high-temperature conditions, while simultaneously maintaining the stability of anthocyanins in 'Zi Feng Che' and 'Chrystal Regal' at the early bloom floral stage. The findings of this research provide new insights into the physiological and biochemical mechanisms by which chrysanthemum flower color responds to high-temperature stress.

Circ-IP6K2 suppresses tumor progression by modulating the miR-1292-5p/CAMK2N1 signal in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is a malignant tumor originating from the epithelial cells of the renal tubules. The clear cell RCC subtype is closely linked to a poor prognosis due to its rapid progression. Circular RNA (circRNA) is a novel class of regulatory RNA molecules that play a role in the development of ccRCC, although their functions have not been fully elucidated. In this study, we identified a significant downregulation of circ-IP6K2 in ccRCC tissues based on data from the GSE100186 dataset. The decreased expression of circ-IP6K2 correlated with the progression of TNM stage and histological grade, and was also associated with decreased overall survival rates in ccRCC patients. Moreover, our findings revealed that circ-IP6K2 expression suppressed proliferation, migration, and invasion capabilities in vitro, and inhibited xenograft growth in vivo. Mechanistically, circ-IP6K2 acted as a sponge for miR-1292-5p in ccRCC cells, which in turn targeted the 3'UTR of CAMK2N1, leading to a decrease in its expression. CAMK2N1 was identified as a tumor suppressor that negatively regulated the ß-catenin/c-Myc oncogenic signaling pathway. Additionally, we confirmed a positive correlation between the expression of circ-IP6K2 and CAMK2N1 in ccRCC. Circ-IP6K2 functions to impede the progression of ccRCC by modulating the miR-1292-5p/CAMK2N1 axis. These findings shed new light on the molecular mechanisms driving ccRCC progression and suggest potential therapeutic targets for the treatment of ccRCC.

A large-aperture, high-power ultrawideband radiation system with beam broadening capacity.

Due to the limited maximum output power of the pulsers based on avalanche transistors, high-power ultrawideband (UWB) radiation systems usually synthesize plenty of modules simultaneously to achieve a high peak effective potential (rEp). However, this would lead to an increased aperture size as well as a narrower beam, which would limit their applications in intentional electromagnetic interference fields. In this paper, a high-power UWB radiation system with beam broadening capacity is developed. To achieve beam broadening in the time domain, a power-law time delay distribution method is proposed and studied by simulation, and then the relative excitation time delays of the modules are optimized to achieve higher rEp and avoid beam splitting in the beam broadening mode. In order to avoid false triggering of the pulser elements when implementing the beam broadening, the mutual coupling effect in the system is analyzed and suppressed by employing onboard high-pass filters, since the mutual coupling effect is much more severe in the low-frequency range. Finally, a radiation system with 36 modules is developed. Measuring results indicate that in the high-rEp mode, the developed system could achieve a maximum effective potential rEp of 313.6 kV and a maximum pulse-repetition-rate of 20 kHz. In the beam broadening mode, its half-peak-power beam width in the H-plane is broadened from the original value of 3.9° to 7.9°, with a maximum rEp of 272.9 kV. The polarization direction of the system could be flexibly adjusted by a built-in motor.

The effect and mechanism of patchouli alcohol on cognitive dysfunction in AD mice induced by Aß1-42 oligomers through AMPK/mTOR pathway.

Alzheimer's disease (AD) is a neurodegenerative brain disorder that progressively impairs long-term and working memory. The function and mechanism of PA(Patchouli alcohol) in improving AD in the external treatment of encephalopathy remain unclear. This study aimed to investigate the therapeutic effect of PA on AD using an Aß1-42 induced AD mouse model with LPS(Lipopolysaccharide) stimulation of BV2 microglial cells. Additionally, we aimed to explore the potential mechanism of PA in enhancing autophagy and reducing neuroinflammation through the AMPK (AMP-activated protein kinase)/mTOR (Mammaliam target of rapamycin) signaling pathway. The Morris water maze was used to assess cognitive function, and cortical and hippocampal tissues were collected for further analysis of the corresponding signaling pathways and inflammatory changes through biological experiments. Our research findings demonstrate that PA has a significant positive impact on cognitive and memory impairments in mice that have been induced with Aß1-42-induced AD. Additionally, PA was also found to revert the activation of microglia induced by LPS. These effects may be attributed to the reduction of neuroinflammation and enhancement of the AMPK/mTOR autophagy pathway. Therefore, PA may serve as an effective therapeutic option to prevent or delay the progression of AD-associated memory dysfunction.

Fluid-responsive tunable metasurfaces for high-fidelity optical wireless communication.

Optical wireless communication (OWC), with its blazing data transfer speed and unparalleled security, is a futuristic technology for wireless connectivity. Despite the significant advancements in OWC, the realization of tunable devices for on-demand and versatile connectivity still needs to be explored. This presents a considerable limitation in utilizing adaptive technologies to improve signal directivity and optimize data transfer. This study proposes a unique platform that utilizes tunable, fluid-responsive multifunctional metasurfaces offering dynamic and unprecedented control over electromagnetic wave manipulation to enhance the performance of OWC networks. We have achieved real-time, on-demand beam steering with vary-focusing capability by integrating the fabricated metasurfaces with different isotropic fluids. Furthermore, the designed metasurfaces are capable of polarization-based switching of the diffracted light beams to enhance overall productivity. Our research has showcased the potential of fluid-responsive tunable metasurfaces in revolutionizing OWC networks by significantly improving transmission reliability and signal quality through real-time adjustments. The proposed methodology is verified by designing and fabricating an all-dielectric metasurface measuring 500 µm × 500 µm and experimentally investigating its fluid-responsive vary-focal capability. By incorporating fluid-responsive properties into spin-decoupled metasurfaces, we aim to develop advanced high-tech optical devices and systems to simplify beam-steering and improve performance, adaptability, and functionality, making the devices suitable for various practical applications.

Structural characteristics of a polysaccharide from Armillariella tabescens and its protective effect on colitis mice via regulating gut microbiota and intestinal barrier function.

A new polysaccharide fraction (ATP) was obtained from Armillariella tabescens mycelium. Structural analysis suggested that the backbone of ATP was →4)-α-D-Glcp(1 â†’ 2)-α-D-Galp(1 â†’ 2)-α-D-Glcp(1 â†’ 4)-α-D-Glcp(1→, which branched at O-3 of →2)-α-D-Glcp(1 â†’ and terminated with T-α-D-Glcp or T-α-D-Manp. Besides, ATP significantly alleviated ulcerative colitis (UC) symptoms and inhibited the production of pro-inflammation cytokines (IL-1ß, IL-6). Meanwhile, ATP could improve colon tissue damage by elevating the expression of MUC2 and tight junction proteins (ZO-1, occludin and claudin-1) levels and enhance intestinal barrier function through inhibiting the activation of MMP12/MLCK/p-MLC2 signaling pathway. Further studies exhibited that ATP could increase the relative abundance of beneficial bacteria such as f. Muribaculacese, g. Muribaculaceae, and g. Alistips, and decrease the relative abundance of g. Desulfovibrio, g. Colidextribacter, g. Ruminococcaceae and g.Oscillibacter, and regulate the level of short-chain fatty acids. Importantly, FMT intervention with ATP-derived microbiome certified that gut microbiota was involved in the protective effects of ATP on UC. The results indicated that ATP was potential to be further developed into promising therapeutic agent for UC.

Prognosis of pediatric BCP-ALL with IKZF1 deletions and impact of intensive chemotherapy: Results of SCCLG-2016 study.

BACKGROUND: IKZF1 deletion (IKZF1del) is associated with poor prognosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). But the prognosis of IKZF1del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP-ALL prognosis has not been determined. METHODS: A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP-ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1del patients were further divided based on chemotherapy intensity for outcome assessments. RESULTS: The BCP-ALL pediatric patients with IKZF1del in south China showed poorer early response. Notably, the DFS and OS for IKZF1del patients were markedly lower than IKZF1wt group (3-year DFS: 88.7% [95% CI: 83.4%-94.0%] vs. 93.5% [95% CI: 92.0%-94.9%], P = .021; 3-year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3-year TRM (6.4% [95% CI: 2.3%-10.5%] vs. 2.9% [95% CI: 1.9%-3.8%], P = .025). However, the 3-year CIR was comparable between the two groups (5.7% [95% CI: 1.8%-9.5%] vs. 3.7% [95% CI: 2.6%-4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3-year DFS was remarkably improved from 53.6% ± 20.1% with non-intensive chemotherapy to 100% with intensive chemotherapy (P = .026). CONCLUSIONS: Pediatric BCP-ALL patients with IKZF1del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1del subset, particularly in IKZFdel patients with BCR::ABL positive.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial.

Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers. Sixty-two, eighteen, and forty-eight participants were enrolled in the single ascending dose (SAD) study, the food effect (FE) study, and the multiple ascending dose (MAD) study, respectively. The study conforms to good clinical practice and the Declaration of Helsinki. Overall, HEC95468 was safe and tolerable; a higher proportion of HEC95468-treated participants reported mild headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal-related treatment-emergent adverse events (TEAEs), similar to the sGC stimulators riociguat and vericiguat. In terms of pharmacokinetic parameters, the maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-t) were dose-proportional over the dose range. Moderate accumulation was observed after multiple administrations of HEC95468. Systolic blood pressure (SBP) and diastolic blood pressure decreased, while 3',5'-cyclic guanosine monophosphate (cGMP) concentration in plasma increased and heart rate was induced. Vasoactive hormones (renin, angiotensin II, and norepinephrine) in plasma were compensatorily elevated after oral administration. These data supported further clinical trials of HEC95468 in the treatment of heart failure and pulmonary arterial hypertension. Systematic Review Registration: http://www.chinadrugtrials.org.cn, identifier CTR20210064.

Rapid solar-driven atmospheric water-harvesting with MAF-4-derived nitrogen-doped nanoporous carbon.

Sorption-based atmospheric water-harvesting (AWH) could help to solve global freshwater scarcity. The search for adsorbents with high water-uptake capacity at low relative humidity, rapid adsorption-desorption kinetics and high thermal conductivity is a critical challenge in AWH. Herein, we report a MAF-4 (aka ZIF-8)-derived nanoporous carbon (NPCMAF-4-800) with multiple N-doped sites, considerable micropore characteristics and inherent photothermal properties, for efficient water production in a relatively arid climate. NPCMAF-4-800 exhibited optimal water-sorption performance of 306 mg g-1 at 40% relative humidity (RH). An excellent sunlight-absorption rate was realized (97%) attributed to its high degree of graphitization. A proof-of-concept device was designed and investigated for the practical harvesting of water from the atmosphere using natural sunlight. NPCMAF-4-800 achieved an unprecedentedly high water production rate of 380 mg g-1 h-1 at 40% RH, and could produce 1.77 L kg-1 freshwater during daylight hours in an outdoor low-humidity climate of ∼25 °C and 40% RH. These findings may shed light on the potential of MOF-derived porous carbons in the AWH field, and inspire the future development of solar-driven water-generation systems.

Oncolytic Newcastle disease virus carrying the IL24 gene exerts antitumor effects by inhibiting tumor growth and vascular sprouting.

The second-leading cause of death, cancer, poses a significant threat to human life. Innovations in cancer therapies are crucial due to limitations in traditional approaches. Newcastle disease virus (NDV), a nonpathogenic oncolytic virus, exhibits multifunctional anticancer properties by selectively infecting, replicating, and eliminating tumor cells. To enhance NDV's antitumor activity, four oncolytic NDV viruses were developed, incorporating IL24 and/or GM-CSF genes at different gene loci using reverse genetics. In vitro experiments revealed that oncolytic NDV virus augmented the antitumor efficacy of the parental virus rClone30, inhibiting tumor cell proliferation, inducing tumor cell fusion, and promoting apoptosis. Moreover, NDV carrying the IL24 gene inhibited microvessel formation in CAM experiments. Evaluation in a mouse model of liver cancer confirmed the therapeutic efficacy of oncolytic NDV viral therapy. Tumors in mice treated with oncolytic NDV virus significantly decreased in size, accompanied by tumor cell detachment and apoptosis evident in pathological sections. Furthermore, oncolytic NDV virus enhanced T cell and dendritic cell production and substantially improved the survival rate of mice with hepatocellular carcinoma, with rClone30-IL24(P/M) demonstrating significant therapeutic effects. This study establishes a basis for utilizing oncolytic NDV virus as an antitumor agent in clinical practice.

Prognostic Value and Immune Signatures of Anoikis-related Genes in Breast Cancer.

From databases of the Cancer Genome Atlas (TCGA) and GSE42568, transcriptome data of breast cancer patients was obtained. Then, anoikis-related genes (ANRGs) were identified and constructed a risk score system. As a threshold value, the median risk score was used to stratify patients into low-risk and high-risk groups. Kaplan-Meier analysis was then conducted to evaluate the prognostic ability of the risk score system, which was validated using GSE7390. Furthermore, we identified potential enrichment of function and tumor immune infiltration in the model. Finally, the biological functions of a risk gene (EPB41L4B) in breast cancer were investigated through in vitro experiments. We constructed a risk score system via 9 prognosis ANRGs (CXCL2, EPB41L4B, SLC7A5, SFRP1, SDC1, BHLHE41, SPINT1, KRT15, and CD24). The Kaplan-Meier analysis showed that both TCGA-BRCA (training set) and GSE7390 (testing set) patients with high-risk status had significantly worse survival outcomes. In addition, the calibration plots were in good agreement with the prognosis prediction. Breast cancer patients with immunosuppressive microenvironment could be screened using risk groups since risk scores were correlated negatively with ESTIMATE score, tumor-infiltration lymphocytes, immune checkpoints, and chemotactic factors. Furthermore, cellular viability and cell migration of cancerous breast cells were inhibited and apoptosis was promoted by down-regulation of EPB41L4B gene expression. Based on ANRGs, a 9-gene prognostic model could be developed to predict breast cancer prognosis; moreover, patients of the high-risk group were in an immunosuppressed tumor microenvironment.

Platelet-Drug Conjugates Engineered via One-step Fusion Approach for Metastatic and Postoperative Cancer Treatment.

The exploration of cell-based drug delivery systems for cancer therapy has gained growing attention. Approaches to engineering therapeutic cells with multidrug loading in an effective, safe, and precise manner while preserving their inherent biological properties remain of great interest. Here, we report a strategy to simultaneously load multiple drugs in platelets in a one-step fusion process. We demonstrate doxorubicin (DOX)-encapsulated liposomes conjugated with interleukin-15 (IL-15) could fuse with platelets to achieve both cytoplasmic drug loading and surface cytokine modification with a loading efficiency of over 70 % within minutes. Due to their inherent targeting ability to metastatic cancers and postoperative bleeding sites, the engineered platelets demonstrated a synergistic therapeutic effect to suppress lung metastasis and postoperative recurrence in mouse B16F10 melanoma tumor models.

Quorum sensing gene lasR promotes phage vB_Pae_PLY infection in Pseudomonas aeruginosa.

BACKGROUND: Quorum sensing (QS) is a cell density-based intercellular communication system that controls virulence gene expression and biofilm formation. In Pseudomonas aeruginosa (P. aeruginosa), the LasR system sits at the top of the QS hierarchy and coordinates the expression of a series of important traits. However, the role of lasR in phage infection remains unclear. This study aims to investigate the role of lasR QS in phage infection. METHODS: The P. aeruginosa phage was isolated from sewage, and its biological characteristics and whole genome were analyzed. The adsorption receptor was identified via a phage adsorption assay. Following lasR gene knockout, the adsorption rate and bactericidal activity of phage were analyzed. Finally, real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to explore how lasR promoting phage infection. RESULTS: The lytic phage vB_Pae_PLY was isolated and lipopolysaccharide (LPS) was identified as its adsorption receptor. The adsorption rate and bactericidal activity of vB_Pae_PLY were reduced after lasR knockout. RT-qPCR results showed that the expression of galU, a key gene involved in LPS synthesis, was down-regulated, and several genes related to type IV pili (T4P) were also down-regulated in the lasR mutant PaΔlasR. CONCLUSIONS: The study showed that QS lasR may promote phage vB_Pae_PLY infection by involving in the synthesis of LPS and T4P. This study provides an example of QS in promoting phage infection and deepens the understanding of phage-bacteria interactions.

Feedback of chain elongation microorganisms on iron-based conductive materials: Enhanced microbial functions and biotoxicity adaptation mechanisms.

Despite the increased research efforts aimed at understanding iron-based conductive materials (CMs) for facilitating chain elongation (CE) to produce medium chain fatty acids (MCFAs), the impact of these materials on microbial community functions and the adaptation mechanisms to their biotoxicity remain unclear. This study found that the supply of zero-valent iron (ZVI) and magnetite enhanced the MCFAs carbon-flow distribution by 26 % and 52 %, respectively. Metagenomic analysis revealed the upregulation of fatty acid metabolism, pyruvate metabolism and ABC transporters with ZVI and magnetite. The predominant functional microorganisms were Massilibacterium and Tidjanibacter with ZVI, and were Petrimonas and Candidatus_Microthrix with magnetite. Furthermore, it was demonstrated that CE microorganisms respond and adapt to the biotoxicity of iron-based CMs by adjusting Two-component system and Quorum sensing for the first time. In summary, this study provided a new deep-insight on the feedback mechanisms of CE microorganisms on iron-based CMs.

Upgrading soybean dreg to caproate via intermediate of lactate and mediator of biochar.

To address the environmental hazards posed by high-yield soybean dreg (SD), a high-value strategy is firstly proposed by synthesizing caproate through chain elongation (CE). Optimized conditions for lactate-rich broth as intermediate, utilizing 50 % inoculum ratio, 40 g/L substrate concentration, and pH 5, resulting in 2.05 g/L caproate from direct fermentation. Leveraging lactate-rich broth supplemented with ethanol, caproate was optimized to 2.76 g/L under a refined electron donor to acceptor of 2:1. Furthermore, incorporating 20 g/L biochar elevated caproate production to 3.05 g/L and significantly shortened the lag phase. Mechanistic insights revealed that biochar's surface-existed quinone and hydroquinone groups exhibit potent redox characteristics, thereby facilitating electron transfer. Moreover, biochar up-regulated the abundance of key genes involved in CE process (especially fatty acids biosynthesis pathway), also enriching Lysinibacillus and Pseudomonas as an unrecognized cooperation to CE. This study paves a way for sustainable development of SD by upgrading to caproate.

An AS-OCT image dataset for deep learning-enabled segmentation and 3D reconstruction for keratitis.

Infectious keratitis is among the major causes of global blindness. Anterior segment optical coherence tomography (AS-OCT) images allow the characterizing of cross-sectional structures in the cornea with keratitis thus revealing the severity of inflammation, and can also provide 360-degree information on anterior chambers. The development of image analysis methods for such cases, particularly deep learning methods, requires a large number of annotated images, but to date, there is no such open-access AS-OCT image repository. For this reason, this work provides a dataset containing a total of 1168 AS-OCT images of patients with keratitis, including 768 full-frame images (6 patients). Each image has associated segmentation labels for lesions and cornea, and also labels of iris for full-frame images. This study provides a great opportunity to advance the field of image analysis on AS-OCT images in both two-dimensional (2D) and three-dimensional (3D) and would aid in the development of artificial intelligence-based keratitis management.