LASSO-Based Identification of Risk Factors and Development of a Prediction Model for Sepsis Patients.

Objective: The objective of this study was to utilize LASSO regression (Least Absolute Shrinkage and Selection Operator Regression) to identify key variables in septic patients and develop a predictive model for intensive care unit (ICU) mortality. Methods: We conducted a cohort consisting of septic patients admitted to the ICU between December 2016 and July 2019. The disease severity and laboratory index were analyzed using LASSO regression. The selected variables were then used to develop a model for predicting ICU mortality. AUCs of ROCs were applied to assess the prediction model, and the accuracy, sensitivity and specificity were calculated. Calibration were also used to assess the actual and predicted values of the predictive model. Results: A total of 1733 septic patients were included, among of whom 382 (22%) died during ICU stay. Ten variables, namely mechanical ventilation (MV) requirement, hemofiltration (HF) requirement, norepinephrine (NE) requirement, septicemia, multiple drug-resistance infection (MDR), thrombocytopenia, hematocrit, red-cell deviation width coefficient of variation (RDW-CV), C-reactive protein (CRP), and antithrombin (AT) III, showed the strongest association with sepsis-related mortality according to LASSO regression. When these variables were combined into a predictive model, the area under the curve (AUC) was found to be 0.801. The AUC of the validation group was 0.791. The specificity of the model was as high as 0.953. Within the probability range of 0.25 to 0.90, the predictive performance of the model surpassed that of individual predictors within the cohort. Conclusion: Our findings suggest that a predictive model incorporating the variables of MV requirement, HF requirement, NE requirement, septicemia, MDR, thrombocytopenia, HCT, RDW-CV, CRP, and AT III exhibiting an 80% likelihood of predicting ICU mortality in sepsis and demonstrates high accuracy.

Rational Design of Three Dimensional Hollow Heterojunctions for Efficient Photocatalytic Hydrogen Evolution Applications.

The efficiency of photocatalytic hydrogen evolution is currently limited by poor light adsorption, rapid recombination of photogenerated carriers, and ineffective surface reaction rate. Although heterojunctions with innovative morphologies and structures can strengthen built-in electric fields and maximize the separation of photogenerated charges. However, how to rational design of novel multidimensional structures to simultaneously improve the above three bottleneck problems is still a research imperative. Herein, a unique Cu2O─S@graphene oxide (GO)@Zn0.67Cd0.33S Three dimensional (3D) hollow heterostructure is designed and synthesized, which greatly extends the carrier lifetime and effectively promotes the separation of photogenerated charges. The H2 production rate reached 48.5 mmol g-1 h-1 under visible light after loading Ni2+ on the heterojunction surface, which is 97 times higher than that of pure Zn0.67Cd0.33S nanospheres. Furthermore, the H2 production rate can reach 77.3 mmol g-1 h-1 without cooling, verifying the effectiveness of the photothermal effect. Meanwhile, in situ characterization and density flooding theory calculations reveal the efficient charge transfer at the p-n 3D hollow heterojunction interface. This study not only reveals the detailed mechanism of photocatalytic hydrogen evolution in depth but also rationalizes the construction of superior 3D hollow heterojunctions, thus providing a universal strategy for the materials-by-design of high-performance heterojunctions.

Secoisolariciresinol diglucoside regulates estrogen receptor expression to ameliorate OVX-induced osteoporosis.

OBJECTIVE: Secoisolariciresinol diglucoside (SDG) is a phytoestrogen that has been reported to improve postmenopausal osteoporosis (PMOP) caused by estrogen deficiency. In our work, we aimed to investigate the mechanism of SDG in regulating the expressions of ERs on PMOP model rats. METHODS: Ovariectomization (OVX) was used to establish PMOP model in rats. The experiment was allocated to Sham, OVX, SDG and raloxifene (RLX) groups. After 12-week treatment, micro-CT was used to detect the transverse section of bone. Hematoxylin and Eosin staining and Safranine O-Fast Green staining were supplied to detect the femur pathological morphology of rats. Estradiol (E2), interleukin-6 (IL-6), bone formation and bone catabolism indexes in serum were detected using ELISA. Alkaline phosphatase (ALP) staining was used to detect the osteogenic ability of chondrocytes. Immunohistochemistry and Western blot were applied to detect the protein expressions of estrogen receptors (ERs) in the femur of rats. RESULTS: Compared with the OVX group, micro-CT results showed SDG could lessen the injury of bone and improve femoral parameters, including bone mineral content (BMC) and bone mineral density (BMD). Pathological results showed SDG could reduce pathological injury of femur in OVX rats. Meanwhile, SDG decreased the level of IL-6 and regulated bone formation and bone catabolism indexes. Besides, SDG increased the level of E2 and conversed OVX-induced decreased the expression of ERα and ERß. CONCLUSION: The treatment elicited by SDG in OVX rats was due to the reduction of injury and inflammation and improvement of bone formation index, via regulating the expression of E2 and ERs.

Porous nanosheet-nanosphere@nanosheet FeNi2-LDH@FeNi2S4 core-shell heterostructures for asymmetric supercapacitors.

Transition bimetallic sulphides have emerged as important electrode materials for supercapacitors owing to their low toxicity, environmental friendliness, cost-effectiveness, multiple oxidation states, high natural abundance, flexible structure, and high theoretical specific capacitance. Herein, a porous nanosheet-nanosphere@nanosheet FeNi2-LDH@FeNi2S4 (FNLDH@FNS) core-shell heterostructure was directly prepared on nickel foam (NF) via a two-step hydrothermal method. The prepared electrode material exhibits an outstanding electrochemical performance. The specific capacity (Cs) values are 806 and 450 C g-1 at current density (Dc) values of 1 and 6 A g-1, respectively, revealing a satisfactory magnification performance. In addition, the FNLDH@FNS electrode exhibits a long cycle life with an supercapacitor (SC) retention rate of 92.3% after 5000 cycles at a Dc of 6 A g-1. The FNLDH@FNS//activated carbon (AC) asymmetric SC assembled with FNLDH@FNS (positive electrode) and activated carbon (AC, negative electrode) displays an energy density (Ed) of 36.67 Wh kg-1 and a power density (Pd) of 775.17 W kg-1.

Development and validation of a prediction model for postoperative intensive care unit admission in patients with non-cardiac surgery.

BACKGROUND: Accurately forecasting patients admitted to the intensive care units (ICUs) after surgery may improve clinical outcomes and guide the allocation of expensive and limited ICU resources. However, studies on predicting postoperative ICU admission in non-cardiac surgery have been limited. OBJECTIVE: To develop and validate a prediction model combining pre- and intraoperative variables to predict ICU admission after non-cardiac surgery. METHODS: This study is based on data from the Vital Signs DataBase (VitalDB) database. Predictors were selected using the least absolute shrinkage and selection operator regression method and logistic regression to develop a nomogram and an online web calculator. The model was internally verified by 1000-Bootstrap resampling. Performance of model was evaluated using area under the receiver operating characteristic curve (AUC), calibration curve and Brier score. The Youden's index was used to find the optimal nomogram's probability threshold. Clinical utility was assessed by decision curve analysis. RESULTS: This study included 5216 non-cardiac surgery patients; of these, 812 (15.6%) required postoperative ICU admission. Potential predictors included age, ASA classification, surgical department, emergency surgery, preoperative albumin level, preoperative urea nitrogen level, intraoperative crystalloid, intraoperative transfusion, intraoperative catheterization, and surgical time. A nomogram was constructed with an AUC of 0.917 (95% CI: 0.907-0.926) and a Brier score of 0.077. The Bootstrap-adjusted AUC was 0.914; the adjusted Brier score was 0.078. The calibration curve showed good agreement between predicted and actual probabilities; and the decision curve indicated clinical usefulness. Finally, we established an online web calculator for clinical application (https://xuzhikun.shinyapps.io/postopICUadmission1/). CONCLUSION: We developed and internally validated an easy-to-use nomogram for predicting ICU admission after non-cardiac surgery.

Corrigendum: Self-assembling and pH-Responsive protein nanoparticle as potential platform for targeted tumor therapy.

[This corrects the article DOI: 10.3389/fmolb.2023.1172100.].

Self-assembling and pH-responsive protein nanoparticle as potential platform for targeted tumor therapy.

Frequent injections at high concentrations are often required for many therapeutic proteins due to their short in vivo half-life, which usually leads to unsatisfactory therapeutic outcomes, adverse side effects, high cost, and poor patient compliance. Herein we report a supramolecular strategy, self-assembling and pH regulated fusion protein to extend the in vivo half-life and tumor targeting ability of a therapeutically important protein trichosanthin (TCS). TCS was genetically fused to the N-terminus of a self-assembling protein, Sup35p prion domain (Sup35), to form a fusion protein of TCS-Sup35 that self-assembled into uniform spherical TCS-Sup35 nanoparticles (TCS-Sup35 NP) rather than classic nanofibrils. Importantly, due to the pH response ability, TCS-Sup35 NP well retained the bioactivity of TCS and possessed a 21.5-fold longer in vivo half-life than native TCS in a mouse model. As a result, in a tumor-bearing mouse model, TCS-Sup35 NP exhibited significantly improved tumor accumulation and antitumor activity without detectable systemic toxicity as compared with native TCS. These findings suggest that self-assembling and pH responding protein fusion may provide a new, simple, general, and effective solution to remarkably improve the pharmacological performance of therapeutic proteins with short circulation half-lives.

A {Cu6}-added polyoxometalate cluster-organic framework: synthesis, structure and application as a solid support for enzyme immobilization.

A new two-dimensional {Cu6}-added polyoxometalate cluster-organic framework (Cu-POMCOF) was prepared by a hydrothermal method from lacunary polyoxoanions and was applied as a solid support for immobilizing MP-11 and Cyt c. The biocomposite complex exhibits higher stability and catalytic activity than the original free enzyme.

The deubiquitinase UCHL1 negatively controls osteoclastogenesis by regulating TAZ/NFATC1 signalling.

The ubiquitin‒proteasome system (UPS) plays a key role in maintaining protein homeostasis and bone remodelling. However, the role of deubiquitinating enzymes (DUBs) in bone resorption is still not well defined. Here, we identified the deubiquitinase ubiquitin C-terminal hydrolase 1 (UCHL1) as a negative regulator of osteoclastogenesis by using the GEO database, proteomic analysis, and RNAi. Osteoclast-specific UCHL1 conditional knockout mice exhibited a severe osteoporosis phenotype in an ovariectomized model. Mechanistically, UCHL1 deubiquitinated and stabilized the transcriptional coactivator with PDZ-binding motif (TAZ) at the K46 residue, thereby inhibiting osteoclastogenesis. The TAZ protein underwent K48-linked polyubiquitination, which was degraded by UCHL1. As a substrate of UCHL1, TAZ regulates NFATC1 through a nontranscriptional coactivator function by competing with calcineurin A (CNA) for binding to NFATC1, which inhibits NFATC1 dephosphorylation and nuclear transport to impede osteoclastogenesis. Moreover, overexpression of UCHL1 locally alleviated acute and chronic bone loss. These findings suggest that activating UCHL1 may serve as a novel therapeutic approach targeting bone loss in various bone pathological states.

Efficient Doping Induced by Charge Transfer at the Hetero-Interface to Enhance Photocatalytic Performance.

The construction of heterojunction photocatalysts is an effective method to improve photocatalytic efficiency since the potential gradient and built-in electron field established at the junction could enhance the efficiency of charge separation and interfacial charge transfer. Nevertheless, heterojunction photocatalysts with strong built-in electron fields remain difficult to build since the two adjacent constitutes must be satisfied with an appropriate band alignment, redox potential, and carrier concentration gradient. Here, an efficient charge transfer-induced doping strategy is proposed to enhance the heterojunction built-in electron field for stable and efficient photocatalytic performance. Carrier transfer tests show that the rectification ratio of the n-TiO2-X/n-BiOI heterojunction is significantly enhanced after being coated with graphene oxide (GO). Consequently, both the hydrogen production and photodegradation performance of the GO composite heterojunction are considerably enhanced compared with pure TiO2-X, BiOI, and n-TiO2-X/n-BiOI. This work provides a facile method to prepare heterojunction photocatalysts with a high catalytic activity.

Efficient and durable S-doped Ni/FeOOH electrocatalysts for oxygen evolution reactions.

It is important to develop highly efficient and durable Earth-abundant oxygen evolution reaction (OER) electrocatalysts by an energy- and time-saving strategy. Herein, a facile strategy was used to synthesize S-doped nickel-iron oxyhydroxide (S-Ni/FeOOH) nanoparticles on nickel-iron foam (NFF) (S-Ni/FeOOH@NFF), which exhibits a striking enhancement of OER performance compared to Ni/FeOOH@NFF. The free-standing S-Ni/FeOOH@NFF electrode possesses a low overpotential of 229 mV at a current density of 10 mA cm-2, which is 180 mV lower than that of Ni/FeOOH@NFF. In addition, the electrode was also remarkably stable. The current density still remains at 95% after 150 h at a high current density of 100 mA cm-2.

Transcriptome analysis of PK-15 cells expressing CSFV NS4A.

BACKGROUND: Classical swine fever (CSF) is a severe disease of pigs that results in huge economic losses worldwide and is caused by classical swine fever virus (CSFV). CSFV nonstructural protein 4 A (NS4A) plays a crucial role in infectious CSFV particle formation. However, the function of NS4A during CSFV infection is not well understood.  RESULTS: In this study, we used RNA-seq to investigate the functional role of CSFV NS4A in PK-15 cells. A total of 3893 differentially expressed genes (DEGs) were identified in PK-15 cells expressing NS4A compared to cells expressing the empty vector (NC). Twelve DEGs were selected and further verified by RT‒qPCR. GO and KEGG enrichment analyses revealed that these DEGs were associated with multiple biological functions, including cell adhesion, apoptosis, host defence response, the inflammatory response, the immune response, and autophagy. Interestingly, some genes associated with host immune defence and inflammatory response were downregulated, and some genes associated with host apoptosis and autophagy were upregulated. CONCLUSION: CSFV NS4A inhibits the innate immune response, and suppresses the expression of important genes associated with defence response to viruses and inflammatory response, and regulates cell adhesion, apoptosis and autophagy.

Anchoring Ce-modified Ni(OH)2 nanoparticles on Ni-MOF nanosheets to enhances the oxygen evolution performance.

Constructing a heterostructure is an efficient strategy to enhance the catalytic activity toward the oxygen evolution reaction (OER). Herein, Ce-modified Ni(OH)2 nanoparticles are anchored on Ni-MOF nanosheets by the electrodeposition strategy, forming a self-supporting electrode of Ce-m-Ni(OH)2@Ni-MOF. The Raman spectrum proves that both Ce(OH)3 and Ce doping exist in Ce-modified Ni(OH)2 nanoparticles. The heterostructure possesses an open nanosheet structure, with a good interaction between Ni-MOF and Ce-m-Ni(OH)2, which enables efficient mass/charge transfer and the synergetic effect between Ni and Ce, leading to a high-performance electrocatalyst. Specifically, Ce-m-Ni(OH)2@Ni-MOF achieves current densities of 50 and 100 mA cm-2 at low overpotentials of 219 and 272 mV, respectively, and retains high activity for at least 30 h.

Formation of NiFe-MOF nanosheets on Fe foam to achieve advanced electrocatalytic oxygen evolution.

2D bimetal metal organic frameworks (MOFs) are recognized as one of the most promising electrocatalysts for the oxygen evolution reaction (OER). Herein, a facile approach was proposed to construct NiFe-MOF nanosheets on Fe foam (FF). As a self-supporting electrode, the NiFe-MOF/FF electrode shows impressive electrocatalytic OER performance. Specifically, it exhibits an ultra-low overpotential of 216 mV to reach a current density of 50 mA cm-2, and outstanding stability (beyond 50 h at 200 mA cm-2). The excellent performances of NiFe-MOF/FF arise from the highly exposed active centers, the excellent conductivity, and the synergy effect between Ni and Fe. This research provides a promising strategy for the synthesis of multi-metal MOFs as high-efficiency electrocatalysts.

Polyoxometalate-Based Metal-Organic Frameworks as the Solid Support to Immobilize MP-11 Enzyme for Enhancing Thermal and Recyclable Stability.

The immobilization of enzymes has received much attention. Metal-organic framework (MOF) as the adsorbent for enzyme encapsulation provides an effective strategy. However, the encapsulation efficacy is not dependent solely on the specific surface area. Though leading into appropriate substrate with negative charge would enhance the encapsulation efficacy. Polyoxometalates (POMs) as the electron sponge would donate electrons without any structural change. In this study, Keggin-type phosphotungstic acid (PW12) was encapsulated in Zirconium metal-organic framework (PW12@UiO-67) as a heterogeneous adsorbent for the encapsulation of enzyme. Our following data proved that this composite cluster could enhance the adsorption of enzyme and the stability of MP-11 was then significantly improved after immobilization.

Formation of carnation-like ZIF-9 nanostructure to achieve superior electrocatalytic oxygen evolution.

Rational design and controllable synthesis of metal-organic frameworks nanosheets is critical for electrochemical catalysis. Herein, a carnation-like ZIF-9 nanostructure made of nanosheets is grown on nickel foam (ZIF-9/NF) by a simple one-step solvothermal method, the morphology evolution and the electrocatalytic oxygen evolution properties have been investigated by controlling the solvothermal time. The binder-free ZIF-9-d/NF (60 h, solvothermal time is 60 h) electrode delivers efficient electrocatalytic oxygen evolution reaction activity with low overpotentials of 312 and 337 mV at 50 and 100 mA cm-2, respectively. Furthermore, ZIF-9-d/NF (60 h) exhibits excellent stability without obvious attenuation for at least 30 h at 200 mA cm-2. The excellent performances can be attributed to the combination of the highly exposed active sites in the ZIF-9-d nanosheets, as well as the effective electron conduction and mass transfer. This work provides much possibilities for ZIF-9 nanosheets as binder-free electrode for electrocatalyst.

Synthesis and Enhanced Light Photocatalytic Activity of Modulating Band BiOBrXI1-X Nanosheets.

The photocatalysis technique has been proven to be a promising method to solve environmental pollution in situations of energy shortage, and has been intensively investigated in the field of pollutant degradation. In this work, a band structure-controlled solid solution of BiOBrXI1-X (x = 0.00, 0.05, 0.10, 0.15, 0.20, 1.00) with highly efficient light-driven photocatalytic activities was successfully synthesized via simple solvothermal methods. The phase composition, crystal structure, morphology, internal molecular vibration, optical properties, and energy band structure were characterized and analyzed by XRD, SEM, HRTEM, XPS, Raman, and UV Vis DRS. To evaluate the photocatalytic activity of BiOBrXI1-X, rhodamine B was selected as an organic pollutant. In particular, BiOBr0.15I0.85 displayed significantly enhanced photocatalytic activity by virtue of modulating the energy band position, optimizing redox potentials, and accelerating carrier separation. Moreover, the enhancement mechanism was elucidated on the basis of band structure engineering, which provides ideas for the design of highly active photocatalysts for practical application in the fields of environmental issues and energy conservation.

Disrupted intracellular redox balance with enhanced ROS generation and sensitive drug release for cancer therapy.

In this paper, a nanocomposite was constructed to achieve improved photodynamic therapy (PDT) via disrupting the redox balance in cancer cells. Firstly, Sb2Se3 nanorods were synthesized as a new photosensitizer, displaying high photothermal conversion efficiency (45.2%) and reactive oxygen species (ROS) production due to the narrow band gap (1.1 eV) and a good NIR response. Moreover, the mechanism was investigated, demonstrating that dissolved O2 and photoinduced electrons manipulated ROS generation. Then, mesoporous silica was coated outside to improve the biocompatibility and to supply abundant space for the anticancer drug (doxorubicin, DOX). The sensitive Se-Se linker was grafted outside via a silane coupling reaction to block DOX molecules in the mesopores. As we know, the Se-Se group is sensitive to GSH, which can induce Se-Se linker bond breakage and targeted drug release due to the high expression of GSH in tumor cells. What is more, the consumption of intracellular GSH can also disrupt the redox balance in cancer cells, which would promote the PDT efficiency. The high-Z element of Sb possesses a high X-ray attenuation coefficient, giving the composite high contrast in CT imaging. This is associated with thermal imaging and multi-therapy (PDT/PTT/chemotherapy) to reveal the potential application to cancer treatment.

Single Atom Array Mimic on Ultrathin MOF Nanosheets Boosts the Safety and Life of Lithium-Sulfur Batteries.

The development of Li-S batteries is largely impeded by the growth of Li dendrites and polysulfide shuttling. To solve these two problems simultaneously, herein the study reports a "single atom array mimic" on ultrathin metal organic framework (MOF) nanosheet-based bifunctional separator for achieving the highly safe and long life Li-S batteries. In the designed separator, the periodically arranged cobalt atoms coordinated with oxygen atoms (CoO4 moieties) exposed on the surface of ultrathin MOF nanosheets, "single atom array mimic", can greatly homogenize Li ion flux through the strong Li ion adsorption with O atoms at the interface between anode and separator, leading to stable Li striping/plating. Meantime, at the cathode side, the Co single atom array mimic serves as "traps" to suppress polysulfide shuttling by Lewis acid-base interaction. As a result, the Li-S coin cells with the bifunctional separator exhibit a long cycle life with an ultralow capacity decay of 0.07% per cycle over 600 cycles. Even with a high sulfur loading of 7.8 mg cm-2 , an areal capacity of 5.0 mAh cm-2 can be remained after 200 cycles. Moreover, the assembled Li-S pouch cell displays stable cycling performance under various bending angles, demonstrating the potential for practical applications.

Atomically Dispersed Co-P3 on CdS Nanorods with Electron-Rich Feature Boosts Photocatalysis.

The development of highly efficient photocatalytic systems with rapid photogenerated charge separation and high surface catalytic activity is highly desirable for the storage and conversion of solar energy, yet remains a grand challenge. Herein, a conceptionally new form of atomically dispersed Co-P3 species on CdS nanorods (CoPSA-CdS) is designed and synthesized for achieving unprecedented photocatalytic activity for the dehydrogenation of formic acid (FA) to hydrogen. X-ray absorption near edge structure, X-ray photoelectron spectroscopy, and time-resolved photoluminescence results confirm that the Co-P3 species have a unique electron-rich feature, greatly improving the efficiency of photogenerated charge separation through an interface charge effect. The in situ attenuated total reflection infrared spectra reveal that the Co-P3 species can achieve much better dissociation adsorption of FA and activation of CH bonds than traditional sulfur-coordinated Co single atom-loaded CdS nanorods (CoSSA-CdS). These two new features make CoPSA-CdS exhibit the unprecedented 50-fold higher activity in the photocatalytic dehydrogenation of FA than CoSSA-CdS, and also much better activity than the Ru-, Rh-, Pd-, or Pt-loaded CdS. Besides, CoPSA-CdS also shows the highest mass activity (34309 mmol gCo -1 h-1 ) of Co reported to date. First-principles simulation reveals that the Co-P3 species herein can form an active PHCOO intermediate for enhancing the rate-determining dissociation adsorption of FA.