LASSO-Based Machine Learning Algorithm for Prediction of PICS Associated with Sepsis.

Introduction: This study aims to establish a comprehensive, multi-level approach for tackling tropical diseases by proactively anticipating and managing Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) within the initial 14 days of Intensive Care Unit (ICU) admission. The primary objective is to amalgamate a diverse array of indicators and pathogenic microbial data to pinpoint pivotal predictive variables, enabling effective intervention specifically tailored to the context of tropical diseases. Methods: A focused analysis was conducted on 1733 patients admitted to the ICU between December 2016 and July 2019. Utilizing the Least Absolute Shrinkage and Selection Operator (LASSO) regression, disease severity and laboratory indices were scrutinized. The identified variables served as the foundation for constructing a predictive model designed to forecast the occurrence of PICS. Results: Among the subjects, 13.79% met the diagnostic criteria for PICS, correlating with a mortality rate of 38.08%. Key variables, including red-cell distribution width coefficient of variation (RDW-CV), hemofiltration (HF), mechanical ventilation (MV), Norepinephrine (NE), lactic acidosis, and multiple-drug resistant bacteria (MDR) infection, were identified through LASSO regression. The resulting predictive model exhibited a robust performance with an Area Under the Curve (AUC) of 0.828, an accuracy of 0.862, and a specificity of 0.977. Subsequent validation in an independent cohort yielded an AUC of 0.848. Discussion: The acquisition of RDW-CV, HF requirement, MV requirement, NE requirement, lactic acidosis, and MDR upon ICU admission emerges as a pivotal factor for prognosticating PICS onset in the context of tropical diseases. This study highlights the potential for significant improvements in clinical outcomes through the implementation of timely and targeted interventions tailored specifically to the challenges posed by tropical diseases.

Investigating optimal compression approach following radial artery puncture: a retrospective study.

BACKGROUND: The method for compressing hemorrhagic sites after transradial access has been a topic of interest, yet definitive guidelines remain elusive. This study aims to address this gap by optimizing the mechanical compression hemostasis protocol after transradial access. METHODS: This retrospective analysis included 300 patients from the Department of Cerebrovascular Diseases, Shanghai Fourth People's Hospital affiliated to Tongji University, who underwent transradial access for cerebrovascular angiography. Following the procedure, patients received radial artery compression hemostasis using a balloon compressor. They were divided into group A (n=100, continuous deflation) and group B (n=200, intermittent deflation) according to different hemostasis methods. The incidence of bleeding at the puncture site and complications were compared between the two groups. RESULTS: The rate of bleeding at the puncture site was significantly lower in group B (20 out of 200 patients) compared to group A (20 out of 100 patients) (P=0.032). Similarly, the incidence of puncture site complications, such as edema, congestion, and wound infection was lower in group B (5 out of 200 patients) compared to group A (10 out of 100 patients) (P=0.006). CONCLUSION: Four hours of compression with intermittent deflation (group B) emerged as the optimal compression method after transradial access, demonstrating fewer complications at the patient's puncture site.

3D Porous Fibers with Spatial Traps and Excellent Zn2+ Transport Kinetics Enable Stable Zn-Based Aqueous Battery.

Adverse side reactions and uncontrolled Zn dendrites growth are the dominant factors that have restricted the application of Zn ion batteries. Herein, a 3D self-supporting porous carbon fibers (denoted as PCFs) host is developed with "trap" effect to adjust the Zn deposition. The unique open structural design of N-doped carbon can act as the zincophilic sites to induce uniform deposition and inhibit adverse side reactions. More importantly, the porous hollow PCFs host with "trap" effect can induce Zn deposition in the fiber by adjusting the local electric field and current density, thereby increasing the specific energy density of the battery and inhibiting dendrite growth. In addition, the 3D open frameworks can regulate Zn2+ flux to enable outstanding cycling performance at ultra-high current densities. As expected, the PCFs framework guarantees the uniform Zn plating and stripping with an outstanding stability over 6000 cycles at the current density of 40 mA cm-2. And the Zn@PCFs||MnO2 full battery shows an excellent lifespan over 1300 cycles at 2000 mA g-1.

Ca2+-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy upon glucose starvation.

Autophagy is essential for maintaining glucose homeostasis. However, the mechanism by which cells sense and respond to glucose starvation to induce autophagy remains incomplete. Here, we show that calcium serves as a fundamental triggering signal that connects environmental sensing to the formation of the autophagy initiation complex during glucose starvation. Mechanistically, glucose starvation instigates the release of vacuolar calcium into the cytoplasm, thus triggering the activation of Rck2 kinase. In turn, Rck2-mediated Atg11 phosphorylation enhances Atg11 interactions with Bmh1/2 bound to the Snf1-Sip1-Snf4 complex, leading to recruitment of vacuolar membrane-localized Snf1 to the PAS and subsequent Atg1 activation, thereby initiating autophagy. We also identified Glc7, a protein phosphatase-1, as a critical regulator of the association between Bmh1/2 and the Snf1 complex. We thus propose that calcium-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy by controlling Snf1-mediated Atg1 activation in response to glucose starvation.

Nrf2 affects DNA damage repair and cell apoptosis through regulating HR and the intrinsic Caspase-dependent apoptosis pathway in TK6 cells exposed to hydroquinone.

Hydroquinone (HQ) is one of benzene metabolites that can cause oxidative stress damage and Homologous recombination repair (HR). A good deal of reactive oxygen species (ROS) generated by oxidative stress can trigger apoptotic signaling pathways. The nuclear factor erythroid 2-related factor 2 (Nrf2) can regulate the cell response to oxidative stress damage. The aim of this study was to explore whether Nrf2 participate in HQ-induced apoptosis and its mechanism. The findings displayed that HQ triggered HR, promoted Nrf2 transfer into the cell nucleus and induced cell apoptosis, while Nrf2 deficient elevated cell apoptosis, attenuated the expression of PARP1 and RAD51. We also observed that Nrf2 deficient triggered Caspase-9. Thus, we speculated that Nrf2 might participate in HQ-induced cell apoptosis through Caspase-9 dependent pathways. Meanwhile, Nrf2 participated in HQ-induced DNA damage repair by regulating the level of PARP1 and RAD51.

Engineering of Aromatic Naphthalene and Solvent Molecules to Optimize Chemical Prelithiation for Lithium-Ion Batteries.

A cost-effective chemical prelithiation solution, which consists of Li+, polyaromatic hydrocarbon (PAH), and solvent, is developed for a model hard carbon (HC) electrode. Naphthalene and methyl-substituted naphthalene PAHs, namely 2-methylnaphthalene and 1-methylnaphthalene, are first compared. Grafting an electron-donating methyl group onto the benzene ring can decrease electron affinity and thus reduce the redox potential, which is validated by density functional theory calculations. Ethylene glycol dimethyl ether (G1), diethylene glycol dimethyl ether, and triethylene glycol dimethyl ether solvents are then compared. The G1 solution has the highest conductivity and least steric hindrance, and thus the 1-methylnaphthalene/G1 solution shows superior prelithiation capability. In addition, the effects of the interaction time between Li+ and 1-methylnaphthalene in G1 solvent on the electrochemical properties of a prelithiated HC electrode are investigated. Nuclear magnetic resonance data confirm that 10-h aging is needed to achieve a stable solution coordination state and thus optimal prelithiation efficacy. It is also found that appropriate prelithiation creates a more Li+-conducing and robust solid-electrolyte interphase, improving the rate capability and cycling stability of the HC electrode.

Structural modification strategies of triazoles in anticancer drug development.

The triazole functional group plays a pivotal role in the composition of biomolecules with potent anticancer activities, including numerous clinically approved drugs. The strategic utilization of the triazole fragment in the rational modification of lead compounds has demonstrated its ability to improve anticancer activities, enhance selectivity, optimize pharmacokinetic properties, and overcome resistance. There has been significant interest in triazole-containing hybrids in recent years due to their remarkable anticancer potential. However, previous reviews on triazoles in cancer treatment have failed to provide tailored design strategies specific to these compounds. Herein, we present an overview of design strategies encompassing a structure-modification approach for incorporating triazoles into hybrid molecules. This review offers valuable references and briefly introduces the synthesis of triazole derivatives, thereby paving the way for further research and advancements in the field of effective and targeted anticancer therapies.

Role of the PARP1/NF-κB Pathway in DNA Damage and Apoptosis of TK6 Cells Induced by Hydroquinone.

Hydroquinone(HQ) is a widely used industrial raw material and is a topical lightening product found in over-the-counter products. However, inappropriate exposure to HQ can pose certain health hazards. This study aims to explore the mechanisms of DNA damage and cell apoptosis caused by HQ, with a focus on whether HQ activates the nuclear factor-κB (NF-κB) pathway to participate in this process and to investigate the correlation between the NF-κB pathway activation and poly(ADP-ribose) polymerase 1(PARP1). Through various experimental techniques, such as DNA damage detection, cell apoptosis assessment, cell survival rate analysis, immunofluorescence, and nuclear-cytoplasmic separation, the cytotoxic effects of HQ were verified, and the activation of the NF-κB pathway was observed. Simultaneously, the relationship between the NF-κB pathway and PARP1 was verified by shRNA interference experiments. The results showed that HQ could significantly activate the NF-κB pathway, leading to a decreased cell survival rate, increased DNA damage, and cell apoptosis. Inhibiting the NF-κB pathway could significantly reduce HQ-induced DNA damage and cell apoptosis and restore cell proliferation and survival rate. shRNA interference experiments further indicated that the activation of the NF-κB pathway was regulated by PARP1. This study confirmed the important role of the NF-κB pathway in HQ-induced DNA damage and cell apoptosis and revealed that the activation of the NF-κB pathway was mediated by PARP1. This research provides important clues for a deeper understanding of the toxic mechanism of HQ.

Quantitative mapping of the mammalian epitranscriptome.

The epitranscriptome encompasses a diverse array of dynamic and reversible RNA modifications, affecting both coding and noncoding RNAs. Over 170 types of RNA chemical modifications have been identified, underscoring the need for innovative detection methods to deepen our understanding of RNA modification roles and mechanisms. In particular, the base resolution and quantitative information on RNA modifications are critical for understanding the regulation and functions of RNA modifications. Based on detection throughput and principles, existing quantitative RNA modification detection methods can be categorized into two groups, including next-generation sequencing and nanopore direct RNA sequencing. In this review, we focus on methodologies for elucidating the base resolution and stoichiometric information of RNA modifications. In addition, we further discuss the challenges and the potential prospects of the quantitative RNA modification detection methods.

Prenatal triphenyl phosphate exposure impairs placentation and induces preeclampsia-like symptoms in mice.

Triphenyl phosphate (TPhP) is an organophosphate flame retardant that is widely used in many commercial products. The United States Environmental Protection Agency has listed TPhP as a priority compound that requires health risk assessment. We previously found that TPhP could accumulate in the placentae of mice and impair birth outcomes by activating peroxisome proliferator-activated receptor gamma (PPARγ) in the placental trophoblast. However, the underlying mechanism remains unknown. In this study, we used a mouse intrauterine exposure model and found that TPhP induced preeclampsia (PE)-like symptoms, including new on-set gestational hypertension and proteinuria. Immunofluorescence analysis showed that during placentation, PPARγ was mainly expressed in the labyrinth layer and decidua of the placenta. TPhP significantly decreased placental implantation depth and impeded uterine spiral artery remodeling by activating PPARγ. The results of the in vitro experiments confirmed that TPhP inhibited extravillous trophoblast (EVT) cell migration and invasion by activating PPARγ and inhibiting the PI3K-AKT signaling pathway. Overall, our data demonstrated that TPhP could activate PPARγ in EVT cells, inhibit cell migration and invasion, impede placental implantation and uterine spiral artery remodeling, then induce PE-like symptom and impair birth outcomes. Although the exposure doses used in this study was several orders of magnitude higher than human daily intake, our study highlights the placenta as a potential target organ of TPhP worthy of further research.

The single cell immunogenomic landscape after neoadjuvant immunotherapy combined chemotherapy in esophageal squamous cell carcinoma.

Neoadjuvant immunotherapy represents promising strategy in the treatment of esophageal squamous cell carcinoma (ESCC). However, the mechanisms underlying its impact on treatment sensitivity or resistance remain a subject of controversy. In this study, we conducted single-cell RNA and T/B cell receptor (scTCR/scBCR) sequencing of CD45+ immune cells on samples from 10 patients who received neoadjuvant immunotherapy and chemotherapy. We also validated our findings using multiplexed immunofluorescence and analyzed bulk RNA-seq from other cohorts in public database. By integrating analysis of 87357 CD45+ cells, we found GZMK + effector memory T cells (Tem) were relatively enriched and CXCL13+ exhausted T cells (Tex) and regulator T cells (Treg) decreased among responders, indicating a persistent anti-tumor memory process. Additionally, the enhanced presence of BCR expansion and somatic hypermutation process within TNFRSF13B + memory B cells (Bmem) suggested their roles in antigen presentation. This was further corroborated by the evidence of the T-B co-stimulation pattern and CXCL13-CXCR5 axis. The complexity of myeloid cell heterogeneity was also particularly pronounced. The elevated expression of S100A7 in ESCC, as detected by bulk RNA-seq, was associated with an exhausted and immunosuppressive tumor microenvironment. In summary, this study has unveiled a potential regulatory network among immune cells and the clonal dynamics of their functions, and the mechanisms of exhaustion and memory conversion between GZMK + Tem and TNFRSF13B + Bmem from antigen presentation and co-stimulation perspectives during neoadjuvant PD-1 blockade treatment in ESCC.

TET2-STAT3-CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition.

Phenotypic plasticity is a rising cancer hallmark, and lung adeno-to-squamous transition (AST) triggered by LKB1 inactivation is significantly associated with drug resistance. Mechanistic insights into AST are urgently needed to identify therapeutic vulnerability in LKB1-deficient lung cancer. Here, we find that ten-eleven translocation (TET)-mediated DNA demethylation is elevated during AST in KrasLSL-G12D/+; Lkb1L/L (KL) mice, and knockout of individual Tet genes reveals that Tet2 is required for squamous transition. TET2 promotes neutrophil infiltration through STAT3-mediated CXCL5 expression. Targeting the STAT3-CXCL5 nexus effectively inhibits squamous transition through reducing neutrophil infiltration. Interestingly, tumor-infiltrating neutrophils are laden with triglycerides and can transfer the lipid to tumor cells to promote cell proliferation and squamous transition. Pharmacological inhibition of macropinocytosis dramatically inhibits neutrophil-to-cancer cell lipid transfer and blocks squamous transition. These data uncover an epigenetic mechanism orchestrating phenotypic plasticity through regulating immune microenvironment and metabolic communication, and identify therapeutic strategies to inhibit AST.

Detection of ribophagy in yeast and mammals.

Ribophagy, the cellular process wherein ribosomes are selectively self-digested through autophagy, plays a pivotal role in maintaining ribosome turnover. Understanding the molecular regulatory mechanisms governing ribophagy is pivotal to uncover its significance. Consequently, the establishment of methods for detecting ribophagy becomes important. In this protocol, we have optimized, enriched, and advanced existing ribophagy detection techniques, including immunoblotting, fluorescence microscopy, and transmission electron microscopy (TEM), to precisely monitor and quantify ribophagic events. Particularly noteworthy is the introduction of TEM technology for yeast ribophagy detection. In summary, the delineated methods are applicable for detecting ribophagy in both yeast and mammals, laying a solid foundation for further exploring the physiological importance of ribophagy and its potential implications in diverse cellular environments.

Identification of the immune repertoire of γδ T-cell receptors in psoriasis.

The γδ T cells are a subpopulation of T cells that are abundantly found in the skin and mucous membranes. Their reactivity to self-antigens and ability to secrete various cytokines make them a key component in psoriasis development. Although the correlation between the immune repertoire (IR) of γδ T-cell receptors and the occurrence and severity of psoriasis remains incompletely explored, high-throughput sequencing of γδ T cells has led to a deeper understanding of IR in psoriasis. This study investigated the differences between γδ T cells in patients with psoriasis and healthy controls. The γδ T cells were identified via immunofluorescence staining and a correlation analysis was performed according to the psoriasis area and severity index (PASI) scores. The IR sequencing method was used to detect IR in the γδ T-cell receptors. The findings demonstrated more skin γδ T cells in patients with psoriasis, which were positively correlated with the PASI score. There were subtle differences in most variable (V), diversity (D) and joining (J) gene segments and VJ/VDJ combination segments between patients with psoriasis and healthy controls. However, a higher diversity of complementarity-determining region 3 (CDR3) was observed in patients with psoriasis. In summary, the IR of skin γδ T cells was significantly altered in patients with psoriasis, and the diversity in the cell's CDR3 population is a promising biomarker for assessment of psoriasis severity.

TiN/anatase/rutile phase junction obtained by in-situ thermal transformation for efficient photothermal-assisted photocatalytic hydrogen generation.

Phase junctions exhibit great potential in photocatalytic energy conversion, yet the narrow light response region and inefficient charge transfer limit their photocatalytic performance. Herein, an anatase/rutile phase junction modified by plasmonic TiN and oxygen vacancies (TiN/(A-R-TiO2-Ov)) is prepared through an in-situ thermal transformation from TiN for efficient photothermal-assisted photocatalytic hydrogen production for the first time. The content of TiN, oxygen vacancies, and phase components in TiN/(A-R-TiO2-Ov) hybrids can be well-adjusted by tuning the heating time. The as-prepared photocatalysts display a large specific area and wide light absorption due to the synergistic effect of plasmonic excitation, oxygen vacancies, and bandgap excitations. Meanwhile, the multi-interfaces between TiN, anatase, and rutile provide built-in electric fields for efficient separation of photoinduced carriers and hot electron injection via ohmic contact and type-Ⅱ band arrangement. As a result, the TiN/(A-R-TiO2-Ov) photocatalyst shows an excellent photocatalytic hydrogen generation rate of 15.07 mmol/g/h, which is 20.6 times higher than that of titanium dioxide P25. Moreover, temperature-dependent photocatalytic tests reveal that the excellent photothermal conversion caused by plasmonic heating and crystal lattice vibrations in TiN/(A-R-TiO2-Ov) has about 25 % enhancement in photocatalysis (18.84 mmol/g/h). This work provides new inspiration for developing high-performance photocatalysts by optimizing charge transfer and photothermal conversion.

Open-Nanogap-Induced Strong Electromagnetic Enhancement in Au/AgAu Monolayer as a Stable and Uniform SERS Substrate for Ultrasensitive Detection.

Nanogap-based plasmonic metal nanocrystals have been applied in surface-enhanced Raman scattering detection, while the closed and insufficient electromagnetic fields as well as the nonreproducible Raman signal of the substrate greatly restrict the actual application. Herein, a highly uniform Au/AgAu monolayer with abundant nanogaps and huge electromagnetic enhancement is prepared, which shows ultrasensitive and reproducible SERS detection. Au/AgAu with an inner nanogap is first prepared based on Au nanotriangles, and the nanogap is opened from the three tips via a subsequent etching process. The open-gap Au/AgAu displays much higher SERS efficiency than Au and Au/AgAu with an inner nanogap on detecting crystal violet due to the open-gap induced electromagnetic enhancement and improved molecular absorption. Furthermore, the open-gap Au/AgAu monolayer is prepared via interfacial self-assembly, which shows further improved SERS due to the dense and strong hotspots in the nanocavities induced by the electromagnetic coupling between adjacent open gaps. The monolayer possesses excellent signal stability, uniformity, and reproducibility. The analytic enhancement factor and relative standard deviation reach to 2.12 × 108 and 4.65% on detecting crystal violet, respectively. Moreover, the monolayer achieves efficient detection of thiram in apple juice, biphenyl-4-thiol, 4-mercaptobenzoic, melamine, and a mixed solution of four different molecules, showing great promise in practical detection.

Effect of Auxin on Cadmium Toxicity-Induced Growth Inhibition in Solanum lycopersicum.

Auxins play crucial regulatory roles in plants coping with cadmium (Cd) stress. However, the regulatory mechanism by which auxins alleviate Cd toxicity in tomato seedlings remains unclear. Here, we demonstrate that exposure to Cd stress leads to dynamic changes in the auxin response in tomato roots, characterized by an initial increase followed by a subsequent weakening. Under Cd stress, tomato seedlings show primary root- and hypocotyl-growth inhibition, accompanied by the accumulation of Cd and reactive oxygen species (ROS) in the roots. The exogenous application of 1-naphthylacetic acid (NAA) does not mitigate the inhibitory effect of Cd toxicity on primary root growth, but it does significantly enhance lateral root development under Cd stress. Auxin transport inhibitors, such as 1-N-naphthylphthalamic acid (NPA) and 2,3,5-triiodobenoic acid (TIBA), aggravate the growth inhibition of primary roots caused by Cd stress. Additionally, lateral root development was inhibited by NPA. However, applying auxin synthesis inhibitors L-kynurenine (kyn) and yucasin alleviated the tomato root growth inhibition caused by Cd stress; between them, the effect of yucasin was more pronounced. Yucasin mitigates Cd toxicity in tomato seedlings by reducing Cd2+ absorption and auxin accumulation, strengthening ROS scavenging, and reducing cell death in roots. These observations suggest that yucasin potentially mitigates Cd toxicity and improves the tolerance of tomato seedlings to Cd stress.