The m6A-ncRNAs axis in diabetes complications: novel mechanism and therapeutic potential.

Diabetes, a multifaceted metabolic disorder, poses a significant global health burden with its increasing prevalence and associated complications, such as diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, and diabetic angiopathy. Recent studies have highlighted the intricate interplay between N6-methyladenosine (m6A) and non-coding RNAs (ncRNAs) in key pathways implicated in these diabetes complications, like cell apoptosis, oxidative stress, and inflammation. Thus, understanding the mechanistic insights into how m6A dysregulation impacts the expression and function of ncRNAs opens new avenues for therapeutic interventions targeting the m6A-ncRNAs axis in diabetes complications. This review explores the regulatory roles of m6A modifications and ncRNAs, and stresses the role of the m6A-ncRNA axis in diabetes complications, providing a therapeutic potential for these diseases.

Research on the generation and annotation method of thin section images of tight oil reservoir based on deep learning.

The cast thin sections of tight oil reservoirs contain important parameters such as rock mineral composition and content, porosity, permeability and stratigraphic characteristics, which are of great significance for reservoir evaluation. The use of deep learning technology for intelligent identification of thin section images is a development trend of mineral identification. However, the difficulty of making cast thin sections, the complexity of the making process and the high cost of thin section annotation have led to a lack of cast thin section images, which cannot meet the training requirements of deep learning image recognition models. In order to increase the sample size and improve the training effect of deep learning model, we proposed a generation and annotation method of thin section images of tight oil reservoir based on deep learning, by taking Fuyu reservoir in Sanzhao Sag as the target area. Firstly, the Augmentor strategy space was used to preliminarily augment the original images while preserving the original image features to meet the requirements of the model. Secondly, the category attention mechanism was added to the original StyleGAN network to avoid the influence of the uneven number of components in thin sections on the quality of the generated images. Then, the SALM annotation module was designed to achieve semi-automatic annotation of the generated images. Finally, experiments on image sharpness, distortion, standard accuracy and annotation efficiency were designed to verify the advantages of the method in image quality and annotation efficiency.

Construction of a Visible-Light-Response Photocatalysis-Self-Fenton Degradation System of Coupling Industrial Waste Red Mud to Resorcinol-Formaldehyde Resin.

Heterogeneous photocatalysis-self-Fenton technology is a sustainable strategy for treating organic pollutants in actual water bodies with high-fluent degradation and high mineralization capacity, overcoming the limitations of the safety risks caused by adding external iron sources and hazardous chemicals in the homogeneous Fenton reaction and injecting high-intensity energy fields in photo-Fenton reaction. Herein, a photo-self-Fenton system based on resorcinol-formaldehyde (RF) resin and red mud (RM) was established to generate hydrogen peroxide (H2O2) in situ and transform into hydroxy radical (•OH) for efficient degradation of tetracycline (TC) under visible light irradiation. The capturing experiments and electron spin resonance (ESR) confirmed that the hinge for the enhanced performance of this system is the superior H2O2 yield (499 µM) through the oxygen reduction process (ORR) of the two-step single-electron over the resin and the high concentration of •OH due to activation effect of RM. In addition, the Fe2+/Fe3+ cycles are accelerated by photoelectrons to effectively initiate the photo-self-Fenton reaction. Finally, the possible degradation pathways were proposed via liquid chromatography-mass spectrometry (LC-MS). This study provides a new idea for environmental recovery in a waste-based heterogeneous photocatalytic self-Fenton system.

Gallic acid-loaded HFZIF-8 for tumor-targeted delivery and thermal-catalytic therapy.

"Transition" metal-coordinated plant polyphenols are a type of promising antitumor nanodrugs owing to their high biosafety and catalytic therapy potency; however, the major obstacle restricting their clinical application is their poor tumor accumulation. Herein, Fe-doped ZIF-8 was tailored using tannic acid (TA) into a hollow mesoporous nanocarrier for gallic acid (GA) loading. After hyaluronic acid (HA) modification, the developed nanosystem of HFZIF-8/GA@HA was used for the targeted delivery of Fe ions and GA, thereby intratumorally achieving the synthesis of an Fe-GA coordinated complex. The TA-etching strategy facilitated the development of a cavitary structure and abundant coordination sites of ZIF-8, thus ensuring an ideal loading efficacy of GA (23.4 wt%). When HFZIF-8/GA@HA accumulates in the tumor microenvironment (TME), the framework is broken due to the competitive protonation ability of overexpressed protons in the TME. Interestingly, the intratumoral degradation of HFZIF-8/GA@HA provides the opportunity for the in situ "meeting" of GA and Fe ions, and through the coordination of polyhydroxyls assisted by conjugated electrons on the benzene ring, highly stable Fe-GA nanochelates are formed. Significantly, owing to the electron delocalization effect of GA, intratumorally coordinated Fe-GA could efficiently absorb second near-infrared (NIR-II, 1064 nm) laser irradiation and transfer it into thermal energy with a conversion efficiency of 36.7%. The photothermal performance could speed up the Fenton reaction rate of Fe-GA with endogenous H2O2 for generating more hydroxyl radicals, thus realizing thermally enhanced chemodynamic therapy. Overall, our research findings demonstrate that HFZIF-8/GA@HA has potential as a safe and efficient anticancer nanodrug.

Evaluation of hemorrhagic shock and fluid resuscitation in pigs using handless Doppler carotid artery ultrasound.

OBJECTIVE: This study aimed to utilize a hemorrhagic shock pig model to compare two hemodynamic monitoring methods, pulse index continuous cardiac output (PiCCO) and spectral carotid artery Doppler ultrasound (CDU). Additionally, we sought to explore the feasibility of employing CDU as a non-invasive hemodynamic monitoring tool in the context of hemorrhagic shock and fluid resuscitation. DESIGN: Animal experiments. SETTING AND SUBJECTS: Female pigs were selected, and hemorrhagic shock was induced by rapid bleeding through an arterial sheath. INTERVENTIONS: Hemodynamic monitoring was conducted using both PiCCO and CDU during episodes of hemorrhagic shock and fluid resuscitation. MEASUREMENTS AND MAIN RESULTS: Among the 10 female pigs studied, CDU measurements revealed a significant decrease in carotid velocity time integral (cVTI) compared to baseline values under shock conditions. During the resuscitation phase, after the mean arterial pressure (MAP) returned to its baseline level, there was no significant difference between cVTI and baseline values. A similar trend was observed for carotid peak velocity (cPV). The corrected flow time (FTc) exhibited a significant difference only at the time of shock compared to baseline values. In comparison to PiCCO, there was a significant correlation between cVTI and MAP (r = 0.616, P < 0.001), stroke volume (SV) (r = 0.821, P < 0.001), and cardiac index (CI) (r = 0.698, P < 0.001). The carotid Doppler shock index (cDSI) displayed negative correlations with MAP (r = - 0.593, P < 0.001), SV (r = - 0.761, P < 0.001), and CI (r = - 0.548, P < 0.001), while showing a positive correlation with the shock index (SI) (r = 0.647, P < 0.001). CONCLUSIONS: Compared to PiCCO, CDU monitoring can reliably reflect the volume status of hemorrhagic shock and fluid resuscitation. CDU offers the advantages of being non-invasive, providing real-time data, and being operationally straightforward. These characteristics make it a valuable tool for assessing and managing hemorrhagic shock, especially in resource-limited settings.

Fluorinated Hafnium and Zirconium Coenable the Tunable Biodegradability of Core-Multishell Heterogeneous Nanocrystals for Bioimaging.

Upconversion (UC)/downconversion (DC)-luminescent lanthanide-doped nanocrystals (LDNCs) with near-infrared (NIR, 650-1700 nm) excitation have been gaining increasing popularity in bioimaging. However, conventional NIR-excited LDNCs cannot be degraded and eliminated eventually in vivo owing to intrinsic "rigid" lattices, thus constraining clinical applications. A biodegradability-tunable heterogeneous core-shell-shell luminescent LDNC of Na3HfF7:Yb,Er@Na3ZrF7:Yb,Er@CaF2:Yb,Zr (abbreviated as HZC) was developed and modified with oxidized sodium alginate (OSA) for multimode bioimaging. The dynamic "soft" lattice-Na3Hf(Zr)F7 host and the varying Zr4+ doping content in the outmoster CaF2 shell endowed HZC with tunable degradability. Through elaborated core-shell-shell coating, Yb3+/Er3+-coupled UC red and green and DC second near-infrared (NIR-II) emissions were, respectively, enhanced by 31.23-, 150.60-, and 19.42-fold when compared with core nanocrystals. HZC generated computed tomography (CT) imaging contrast effects, thus enabling NIR-II/CT/UC trimodal imaging. OSA modification not only ensured the exemplary biocompatibility of HZC but also enabled tumor-specific diagnosis. The findings would benefit the clinical imaging translation of LDNCs.

Self-Catalyzed Synthesis of Length-Controlled One-Dimensional Nickel Oxide@N-Doped Porous Carbon Nanostructures from Metal Ion Modified Nitrogen Heterocycles for Efficient Lithium Storage.

Transition metal oxides with the merits of high theoretical capacities, natural abundance, low cost, and environmental benignity have been regarded as a promising anodic material for lithium ion batteries (LIBs). However, the severe volume expansion upon cycling and poor conductivity limit their cycling stability and rate capability. To address this issue, NiO embedded and N-doped porous carbon nanorods (NiO@NCNR) and nanotubes (NiO@NCNT) are synthesized by the metal-catalyzed graphitization and nitridization of monocrystalline Ni(II)-triazole coordinated framework and Ni(II)/melamine mixture, respectively, and the following oxidation in air. When applied as an anodic material for LIBs, the NiO@NCNR and NiO@NCNT hybrids exhibit a decent capacity of 895/832 mA h g-1 at 100 mA g-1, high rate capability of 484/467 mA h g-1 at 5.0 A g-1, and good long-term cycling stability of 663/634 mA h g-1 at 600th cycle at 1 A g-1, which are much better than those of NiO@carbon black (CB) control sample (701, 214, and 223 mA h g-1). The remarkable electrochemical properties benefit from the advanced nanoarchitecture of NiO@NCNR and NiO@NCNT, which offers a length-controlled one-dimensional porous carbon nanoarchitecture for effective e-/Li+ transport, affords a flexible carbon skeleton for spatial confinement, and forms abundant nanocavities for stress buffering and structure reinforcement during discharge/charging processes. The rational structural design and synthesis may pave a way for exploring advanced metal oxide based anodic materials for next-generation LIBs.

Targeted Delivery of Active Sites by Oxygen Vacancy-Engineered Bimetal Silicate Nanozymes for Intratumoral Aggregation-Potentiated Catalytic Therapy.

Biodegradable silicate nanoconstructs have aroused tremendous interest in cancer therapeutics due to their variable framework composition and versatile functions. Nevertheless, low intratumoral retention still limits their practical application. In this study, oxygen vacancy (OV)-enriched bimetallic silicate nanozymes with Fe-Ca dual active sites via modification of oxidized sodium alginate and gallic acid (GA) loading (OFeCaSA-V@GA) were developed for targeted aggregation-potentiated therapy. The band gap of silica markedly decreased from 2.76 to 1.81 eV by codoping of Fe3+ and Ca2+, enabling its excitation by a 650 nm laser to generate reactive oxygen species. The OV that occurred in the hydrothermal synthetic stage of OFeCaSA-V@GA can anchor the metal ions to form an atomic phase, offering a massive fabrication method of single-atom nanozymes. Density functional theory results reveal that the Ca sites can promote the adsorption of H2O2, and Fe sites can accelerate the dissociation of H2O2, thereby realizing a synergetic catalytic effect. More importantly, the targeted delivery of metal ions can induce a morphological transformation at tumor sites, leading to high retention (the highest retention rate is 36.3%) of theranostic components in tumor cells. Thus, this finding may offer an ingenious protocol for designing and engineering highly efficient and long-retention nanodrugs.

COMPARISON AMONG PRESEPSIN, PROCALCITONIN, AND C-REACTIVE PROTEIN IN PREDICTING BLOOD CULTURE POSITIVITY AND PATHOGEN IN SEPSIS PATIENTS.

ABSTRACT: Background: Sepsis is caused by the invasion of the bloodstream by microorganisms from local sites of infection, leading to high mortality. This study aimed to compare the predictive ability of the biomarkers presepsin, procalcitonin (PCT), and C-reactive protein for bacteraemia. Methods: In this retrospective, multicentre study, a dataset of patients with sepsis who were prospectively enrolled between November 2017 and June 2021 was analyzed. The performances of the biomarkers for predicting positive blood cultures and infection with specific pathogens were assessed by the areas under the receiver operating characteristic curves (AUCs). The independent effects of the pathogen and foci of infection on presepsin and PCT levels were assessed by linear logistic regression models. Results: A total of 577 patients with 170 positive blood cultures (29.5%) were enrolled. The AUC achieved using PCT levels (0.856) was significantly higher than that achieved using presepsin (0.786, P = 0.0200) and C-reactive protein (0.550, P < 0.0001) levels in predicting bacteraemia. The combined analysis of PCT and presepsin levels led to a significantly higher AUC than the analysis of PCT levels alone for predicting blood culture positivity (0.877 vs. 0.856, P = 0.0344) and gram-negative bacteraemia (0.900 vs. 0.875, P = 0.0216). In a linear regression model, the elevated concentrations of presepsin and PCT were both independently related to Escherichia coli , Klebsiella species, Pseudomonas species, and Streptococcus species infections and Sequential Organ Failure Assessment score. Presepsin levels were also associated with Acinetobacter species and abdominal infection, and PCT levels were positively associated with other Enterobacteriaceae and negatively associated with respiratory infection. Combined analysis of presepsin and PCT levels provided a high sensitivity and specificity in identifying E. coli or Klebsiella species infection. Conclusions: Presepsin and PCT were promising markers for predicting bacteraemia and common pathogens at the time of sepsis onset with a synergistic effect.

Comparison of dose and risk estimates between ISS Partner Agencies for a 30-day lunar mission.

The International Partner Agencies of the International Space Station (ISS) present a comparison of the ionizing radiation absorbed dose and risk quantities used to characterize example missions in lunar space. This effort builds on previous collaborative work that characterizes radiation environments in space to support radiation protection for human spaceflight on ISS in low-Earth orbit (LEO) and exploration missions beyond (BLEO). A "shielded" ubiquitous galactic cosmic radiation (GCR) environment combined with--and separate from--the transient challenge of a solar particle event (SPE) was modelled for a simulated 30-day mission period. Simple geometries of relatively thin and uniform shields were chosen to represent the space vehicle and other available shielding, and male or female phantoms were used to represent the body's self-shielding. Absorbed dose in organs and tissues and the effective dose were calculated for males and females. Risk parameters for cancer and other outcomes are presented for selected organs. The results of this intracomparison between ISS Partner Agencies itself provide insights to the level of agreement with which space agencies can perform organ dosimetry and calculate effective dose. This work was performed in collaboration with the advisory and guidance efforts of the International Commission on Radiological Protection (ICRP) Task Group 115 and will be presented in an ICRP Report.

Space agency-specific standards for crew dose and risk assessment of ionising radiation exposures for the International Space Station.

The Partner Agencies of the International Space Station (ISS) maintain separate career exposure limits and shared Flight Rules that control the ionising radiation exposures that crewmembers can experience due to ambient environments throughout their space missions. In low Earth orbit as well as further out in space, energetic ions referred to as galactic cosmic radiation (GCR) easily penetrate spacecraft and spacecraft contents and consequently are always present at low dose rates. Protons and electrons that are trapped in the Earth's geomagnetic field are encountered intermittently, and a rare energetic solar particle event (SPE) may expose crew to (mostly) energetic protons. Space radiation protection goals are to optimize radiation exposures to maintain deleterious late effects at known and acceptable levels and to prevent any early effects that might compromise crew health and mission success. The conventional radiation protection metric effective dose provides a basic framework for limiting exposures associated with human spaceflight and can be communicated to all stakeholders. Additional metrics and uncertainty analyses are required to understand more completely and to convey nuanced information about potential impacts to an individual astronaut or to a space mission. Missions to remote destinations well beyond low Earth orbit (BLEO) are upcoming and bestow additional challenges that shape design and radiation protection needs. NASA has recently adopted a more permissive career exposure limit based upon effective dose and new restrictions on mission exposures imposed by nuclear technologies. This manuscript reviews the exposure limits that apply to the ISS crewmembers. This work was performed in collaboration with the advisory and guidance efforts of International Commission on Radiological Protection (ICRP) Task Group 115 and will be summarized in an upcoming ICRP Report.

Embedding Atomically Dispersed Manganese/Gadolinium Dual Sites in Oxygen Vacancy-Enriched Biodegradable Bimetallic Silicate Nanoplatform for Potentiating Catalytic Therapy.

Due to their atomically dispersed active centers, single-atom nanozymes (SAzymes) have unparalleled advantages in cancer catalytic therapy. Here, loaded with chlorin e6 (Ce6), a hydrothermally mass-produced bimetallic silicate-based nanoplatforms with atomically dispersed manganese/gadolinium (Mn/Gd) dual sites and oxygen vacancies (OVs) (PMnSA GMSNs-V@Ce6) is constructed for tumor glutathione (GSH)-triggered chemodynamic therapy (CDT) and O2 -alleviated photodynamic therapy. The band gaps of silica are significantly reduced from 2.78 to 1.88 eV by doping with metal ions, which enables it to be excited by a 650 nm laser to produce electron-hole pairs, thereby facilitating the generation of reactive oxygen species. The Gd sites can modulate the local electrons of the atom-catalyzed Mn sites, which contribute to the generation of superoxide and hydroxyl radicals (• OH). Tumor GSH-triggered Mn2+ release can convert endogenous H2 O2 to • OH and realize GSH-depletion-enhanced CDT. Significantly, the hydrothermally generated OVs can not only capture Mn and Gd atoms to form atomic sites but also can elongate and weaken the O-O bonds of H2 O2 , thereby improving the efficacy of Fenton reactions. The degraded Mn2+ /Gd3+ ions can be used as tumor-specific magnetic resonance imaging contrast agents. All the experimental results demonstrate the great potential of PMnSA GMSNs-V@Ce6 as cancer theranostic agent.

A transducer positioning method for transcranial focused ultrasound treatment of brain tumors.

Purpose: As a non-invasive method for brain diseases, transcranial focused ultrasound (tFUS) offers higher spatial precision and regulation depth. Due to the altered path and intensity of sonication penetrating the skull, the focus and intensity in the skull are difficult to determine, making the use of ultrasound therapy for cancer treatment experimental and not widely available. The deficiency can be effectively addressed by numerical simulation methods, which enable the optimization of sonication modulation parameters and the determination of precise transducer positioning. Methods: A 3D skull model was established using binarized brain CT images. The selection of the transducer matrix was performed using the radius positioning (RP) method after identifying the intracranial target region. Simulations were performed, encompassing acoustic pressure (AP), acoustic field, and temperature field, in order to provide compelling evidence of the safety of tFUS in sonication-induced thermal effects. Results: It was found that the angle of sonication path to the coronal plane obtained at all precision and frequency models did not exceed 10° and 15° to the transverse plane. The results of thermal effects illustrated that the peak temperatures of tFUS were 43.73°C, which did not reach the point of tissue degeneration. Once positioned, tFUS effectively delivers a Full Width at Half Maximum (FWHM) stimulation that targets tumors with diameters of up to 3.72 mm in a one-off. The original precision model showed an attenuation of 24.47 ± 6.13 mm in length and 2.40 ± 1.42 mm in width for the FWHM of sonication after penetrating the skull. Conclusion: The vector angles of the sonication path in each direction were determined based on the transducer positioning results. It has been suggested that when time is limited for precise transducer positioning, fixing the transducer on the horizontal surface of the target region can also yield positive results for stimulation. This framework used a new transducer localization method to offer a reliable basis for further research and offered new methods for the use of tFUS in brain tumor-related research.

Comparison of the taste mechanisms of umami and bitter peptides from fermented mandarin fish (Chouguiyu) based on molecular docking and electronic tongue technology.

Unclear taste mechanisms of peptides limit rapid screening of taste peptides with high intensity. In this study, the taste mechanisms of umami and bitter peptides from Chouguiyu were compared. After molecular docking of core umami (NWDDMEK, WFKDEEF, EEEKPKF, DFDDIQK, and DGEKVDF) and bitter (VQDVLKL, VELLKLE, LVVDGVK, VVDLTVR, and VVDGVKL) peptides with T1R1/T1R3 and TASR14, respectively, salt bridges and conventional hydrogen bonds were the main interactions in all taste peptides, in which acidic amino acid residues contributed to the interaction with their receptors. The taste intensity of peptides after solid-phase synthesis was further verified using electronic tongue technology. Spearman correlation analysis showed that docking energy was an important factor for the intensity of taste peptides, while interaction energy and the distance between the binding unit (BU) and the stimulating unit (SU) were also responsible for the bitter intensity. This study provides a theoretical basis to screen novel taste peptides with high taste intensity in fermented foods.

Optimized core-shell lanthanide nanoparticles with ultrabright Ce3+-modulated second near-infrared emission for "lighting" plants.

Second near-infrared (NIR-II, 1000-1700 nm) photon-mediated fluorescence imaging has attracted extensive interest in the field of bioimaging. However, NIR-II fluorescent nanoprobes competent for plant imaging have been rarely developed. Herein, lanthanide-doped nanoparticle (LDNP) optimal core-shell structure and ultrabright NIR-II emission were developed for "lighting" plants. The Ce3+-doped active shell coated on the NaErF4:Tm core enables dual-mode red upconversion (UC) and NIR-II downconversion (DC) emission of LDNPs upon 980 nm laser excitation. Under the optimized doping content, the intensities of red UC and NIR-II DC emission were respectively boosted by 5- and 19-fold those of the core nanoparticles, which endowed LDNPs with ideal NIR-II emissive capabilities for optical imaging of plants. Significantly, the NIR-II fluorescent signal affords much higher signal-to-noise rate than the red UC. LDNPs were modified with polyethyleneimine to enable outstanding hydrophilicty and facilitate their uptake by plants. Arabidopsis thaliana and Nicotiana benthamiana were chosen as plant models for NIR-II imaging studies. The toxic effect of LDNPs after being transported into Brassica rapa chinensis was systematically studied on mice. The NIR-II imaging strategy offers a promising method for studying the uptake and transport of nanoparticles in plants.

Nickel-doped iridium echinus-like nanosheets for stable acidic water splitting.

Nickel-doped iridium echinus-like nanosheets (NiIr-ENS) have a superior acidic oxygen evolution reaction (OER) activity with a TOF of 1.72 s-1 at an overpotential of 300 mV, 8.6-fold higher than that of IrO2.

Exploring plant polyphenols as anti-allergic functional products to manage the growing incidence of food allergy.

The active substances derived from plants have received increasing attention owing to their wide range of pharmacological applications, including anti-tumor, anti-allergic, anti-viral, and anti-oxidative activities. The allergy epidemic is a growing global public health problem that threatens human health and safety. Polyphenols from plants have significant anti-allergic effects and are an important source of anti-allergic drug research and development. Here, we describe recent advances in the anti-allergic efficacy of plant polyphenols, including their comprehensive effects on cellular or animal models. The current issues and directions for future development in this field are discussed to provide a theoretical basis for the development and utilization of these active substances as anti-allergic products.

Over-expression of programmed death-ligand 1 and programmed death-1 on antigen-presenting cells as a predictor of organ dysfunction and mortality during early sepsis: a prospective cohort study.

BACKGROUND: This study aimed to explore the changes of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) expression on antigen-presenting cells (APCs) and evaluate their association with organ failure and mortality during early sepsis. METHODS: In total, 40 healthy controls and 198 patients with sepsis were included in this study. Peripheral blood was collected within the first 24 h after the diagnosis of sepsis. The expression of PD-L1 and PD-1 was determined on APCs, such as B cells, monocytes, and dendritic cells (DCs), by flow cytometry. Cytokines in plasma, such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, and IL-17A were determined by Luminex assay. RESULTS: PD-1 expression decreased significantly on B cells, monocytes, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs) as the severity of sepsis increased. PD-1 expression was also markedly decreased in non-survivors compared with survivors. In contrast, PD-L1 expression was markedly higher on mDCs, pDCs, and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors. The PD-L1 expression on APCs (monocytes and DCs) was weakly related to organ dysfunction and inflammation. The area under the receiver operating characteristic curve (AUC) of the PD-1 percentage of monocytes (monocyte PD-1%)+APACHE II model (0.823) and monocyte PD-1%+SOFA model (0.816) had higher prognostic value than other parameters alone. Monocyte PD-1% was an independent risk factor for 28-day mortality. CONCLUSION: The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs. PD-L1 in monocytes and DCs was weakly correlated with inflammation and organ dysfunction during early sepsis. The combination of SOFA or APACHE II scores with monocyte PD-1% could improve the prediction ability for mortality.

Predictive value of presepsin and acylcarnitines for severity and biliary drainage in acute cholangitis.

BACKGROUND: Bacteremia, which is a major cause of mortality in patients with acute cholangitis, induces hyperactive immune response and mitochondrial dysfunction. Presepsin is responsible for pathogen recognition by innate immunity. Acylcarnitines are established mitochondrial biomarkers. AIM: To clarify the early predictive value of presepsin and acylcarnitines as biomarkers of severity of acute cholangitis and the need for biliary drainage. METHODS: Of 280 patients with acute cholangitis were included and the severity was stratified according to the Tokyo Guidelines 2018. Blood presepsin and plasma acylcarnitines were tested at enrollment by chemiluminescent enzyme immunoassay and ultra-high-performance liquid chromatography-mass spectrometry, respectively. RESULTS: The concentrations of presepsin, procalcitonin, short- and medium-chain acylcarnitines increased, while long-chain acylcarnitines decreased with the severity of acute cholangitis. The areas under the receiver operating characteristic curves (AUC) of presepsin for diagnosing moderate/severe and severe cholangitis (0.823 and 0.801, respectively) were greater than those of conventional markers. The combination of presepsin, direct bilirubin, alanine aminotransferase, temperature, and butyryl-L-carnitine showed good predictive ability for biliary drainage (AUC: 0.723). Presepsin, procalcitonin, acetyl-L-carnitine, hydroxydodecenoyl-L-carnitine, and temperature were independent predictors of bloodstream infection. After adjusting for severity classification, acetyl-L-carnitine was the only acylcarnitine independently associated with 28-d mortality (hazard ratio 14.396; P < 0.001) (AUC: 0.880). Presepsin concentration showed positive correlation with direct bilirubin or acetyl-L-carnitine. CONCLUSION: Presepsin could serve as a specific biomarker to predict the severity of acute cholangitis and need for biliary drainage. Acetyl-L-carnitine is a potential prognostic factor for patients with acute cholangitis. Innate immune response was associated with mitochondrial metabolic dysfunction in acute cholangitis.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04563936.