Prognostic value of the systemic immune-inflammation index in critically ill elderly patients with hip fracture: evidence from MIMIC (2008-2019).

Background: The systemic immune-inflammation index (SII) showed an extensive link between immunological dysfunction and the activation of systemic inflammation. Several studies have confirmed the application of SII to orthopedic diseases. However, the significance of SII in critically ill elderly individuals with hip fracture who require intensive care unit (ICU) admission is not yet known. This study centered on exploring the relationship between SII and clinical outcomes among critically ill elderly hip fracture individuals. Methods: The study centered around elderly patients experiencing severe illness following hip fractures and requiring admission to the ICU. These patients from the MIMIC-IV database formed the basis of this study's cohort. We stratified them into quartiles according to their SII levels. The results involved the mortality at 30 days and 1 year post-admission. Then we employ Cox proportional hazards regression analysis as well as restricted cubic splines to explore the association between the SII and clinical results in critically ill elderly patients with hip fracture. Results: The study encompassed 991 participants, among whom 63.98% identified as females. Notably, the mortality rates attributed to any cause within 30 days and 1 year after hospitalization stood at 19.68 and 33.40%, respectively. The multivariate Cox proportional hazards model disclosed a significant correlation between an elevated SII and all-cause mortality. Following adjustments for confounding variables, individuals with a high SII showed a notable correlation with 30-day mortality [adjusted hazard ratio (HR), 1.065; 95% confidence interval (CI), 1.044-1.087; p < 0.001] and 1-year mortality (adjusted HR, 1.051; 95% CI, 1.029-1.074; p < 0.001). Furthermore, the analysis of restricted cubic splines demonstrated a progressive increase in the risk of all-cause death as the SII value rose. Conclusion: Among critically ill elderly patients with hip fracture, the SII exhibits a non-linear association that positively correlates with both 30-day and 1-year all-cause mortality rates. The revelation indicates that the SII may play a vital role in identifying patients with hip fractures who face an escalated risk of mortality due to any cause.

In Vitro Propagation Technology for the Endangered Aquatic Species Nymphoides coronata.

Nymphoides coronata is an endangered aquatic plant species with significant medicinal and ecological importance. To preserve N. coronata from going extinct, we need to provide seedlings and efficient multiplication techniques so that it can be extensively studied. This study aimed to identify the most suitable sterilization treatment, growth medium, and substrate for the cultivation and propagation of N. coronata. Ethanol sterilization, fungicide treatment, and sterile water washing were the most important sterilization steps. A combination of 6-benzylaminopurine (6-BA) and indoleacetic acid (IAA) was the most suitable medium for bud induction and shoot proliferation. The use of α-naphthaleneacetic acid (NAA) increased the rooting rate and rooting time compared to indole-3-butyric acid (IBA). Increasing the concentration of NAA from 0.5 to 1.0 mg/L increased the rooting rate from 78 to 100% and reduced the rooting time from 7 to 5 days. The survival rate of N. coronata seedlings was 100% in a mixture of red soil and sand (1:1, w/w). As a result, the procedure mentioned above could potentially be used to safely propagate this rare species on a large scale. These findings provide valuable insights into the optimal conditions for the successful cultivation and propagation of N. coronata, which can contribute to the conservation and sustainable use of this important rare plant species.

SETDB1 deletion causes DNA demethylation and upregulation of multiple zinc-finger genes.

BACKGROUND: SETDB1 (SET domain bifurcated-1) is a histone H3-lysine 9 (H3K9)-specific methyltransferase that mediates heterochromatin formation and repression of target genes. Despite the assumed functional link between DNA methylation and SETDB1-mediated H3K9 trimethylations, several studies have shown that SETDB1 operates autonomously of DNA methylation in a region- and cell-specific manner. This study analyzes SETDB1-null HAP1 cells through a linked methylome and transcriptome analysis, intending to explore genes controlled by SETDB1-involved DNA methylation. METHODS AND RESULTS: We investigated SETDB1-mediated regulation of DNA methylation and gene transcription in human HAP1 cells using reduced-representation bisulfite sequencing (RRBS) and RNA sequencing. While two-thirds of differentially methylated CpGs (DMCs) in genic regions were hypomethylated in SETDB1-null cells, we detected a plethora of C2H2-type zinc-finger protein genes (C2H2-ZFP, 223 of 749) among the DMC-associated genes. Most C2H2-ZFPs with DMCs in their promoters were found hypomethylated in SETDB1-KO cells, while other non-ZFP genes with promoter DMCs were not. These C2H2-ZFPs with DMCs in their promoters were significantly upregulated in SETDB1-KO cells. Similarly, C2H2-ZFP genes were upregulated in SETDB1-null 293T cells, suggesting that SETDB1's function in ZFP gene repression is widespread. There are several C2H2-ZFP gene clusters on chromosome 19, which were selectively hypomethylated in SETDB1-KO cells. CONCLUSIONS: SETDB1 collectively and specifically represses a substantial fraction of the C2H2-ZFP gene family. Through the en-bloc silencing of a set of ZFP genes, SETDB1 may help establish a panel of ZFP proteins that are expressed cell-type specifically and thereby can serve as signature proteins for cellular identity.

Concurrent Infection with Clade 2.3.4.4b Highly Pathogenic Avian Influenza H5N6 and H5N1 Viruses, South Korea, 2023.

Highly pathogenic avian influenza H5N6 and H5N1 viruses of clade 2.3.4.4b were simultaneously introduced into South Korea at the end of 2023. An outbreak at a broiler duck farm consisted of concurrent infection by both viruses. Sharing genetic information and international surveillance of such viruses in wild birds and poultry is critical.

Biomimetic piezoelectric nanomaterial-modified oral microrobots for targeted catalytic and immunotherapy of colorectal cancer.

Lactic acid (LA) accumulation in the tumor microenvironment poses notable challenges to effective tumor immunotherapy. Here, an intelligent tumor treatment microrobot based on the unique physiological structure and metabolic characteristics of Veillonella atypica (VA) is proposed by loading Staphylococcus aureus cell membrane-coating BaTiO3 nanocubes (SAM@BTO) on the surface of VA cells (VA-SAM@BTO) via click chemical reaction. Following oral administration, VA-SAM@BTO accurately targeted orthotopic colorectal cancer through inflammatory targeting of SAM and hypoxic targeting of VA. Under in vitro ultrasonic stimulation, BTO catalyzed two reduction reactions (O2 → •O2- and CO2 → CO) and three oxidation reactions (H2O → •OH, GSH → GSSG, and LA → PA) simultaneously, effectively inducing immunogenic death of tumor cells. BTO catalyzed the oxidative coupling of VA cells metabolized LA, effectively disrupting the immunosuppressive microenvironment, improving dendritic cell maturation and macrophage M1 polarization, and increasing effector T cell proportions while decreasing regulatory T cell numbers, which facilitates synergetic catalysis and immunotherapy.

Advancing treatment strategies for posterior malleolar malunion: The ankle dislocation method.

BACKGROUND: This study aimed to assess the radiological and clinical outcomes of treatment using the ankle dislocation method for posterior malleolar malunion. METHOD: Thirty-one patients with posterior malleolar malunion who underwent treatment using the ankle dislocation method from May 2015 to October 2021 were retrospectively analyzed. Key outcome measures were radiographic parameters (articular step-off, tibiofibular clear space, fibular length, tibial lateral surface angle, and ankle osteoarthritis), clinical scores (American Orthopaedic Foot and Ankle Society ankle-hindfoot scale and Visual Analogue Scale), and patient satisfaction rate. RESULT: Preoperative computed tomography revealed that Bartoní cek types 3 and 4 accounted for 64.5 % (n = 20) of total cases. Most posterior malleolar malunions were accompanied by depressed intercalary fragments (61.2 % [n = 19]). At the final follow-up, radiographic parameters and clinical scores showed significant improvements postoperatively (P < 0.05), with a high patient satisfaction rate of 77.4 %. Subgroup analysis revealed that the posterior malleolar fracture morphology significantly affected postoperative pain, particularly in more complex fractures (P < 0.001). CONCLUSION: The ankle dislocation method effectively exposes the distal tibial articular surface and facilitates the anatomical restoration of joint congruity under direct vision. This approach substantially improves the clinical and imaging outcomes in patients with complex posterior malleolar malunion. LEVELS OF EVIDENCE: Level IV, retrospective case series.

Development and evaluation of a multiplex real-time RT-PCR assay for simultaneous detection of H5, H7, and H9 subtype avian influenza viruses.

H5, H7 and H9 are the major subtypes of avian influenza virus (AIV) that cause economic losses in the poultry industry and sporadic zoonotic infection. Early detection of AIV is essential for preventing disease spread. Therefore, molecular diagnosis and subtyping of AIV via real-time RT-PCR (rRT-PCR) is preferred over other classical diagnostic methods, such as egg inoculation, RT-PCR and HI test, due to its high sensitivity, specificity and convenience. The singleplex rRT-PCRs for the Matrix, H5 and H7 gene used for the national surveillance program in Korea have been developed in 2017; however, these methods were not designed for multiplexing, and does not reflect the sequences of currently circulating strains completely. In this study, the multiplex H5/7/9 rRT-PCR assay was developed with sets of primers and probe updated or newly designed to simultaneously detect the H5, H7 and H9 genes. Multiplex H5/7/9 rRT-PCR showed 100% specificity without cross-reactivity with other subtypes of AIVs and avian disease-causing viruses or bacteria, and the limit of detection was 1-10 EID50/0.1 ml (50% egg infectious dose). Artificial mixed infections with the three different subtypes could be detected accurately with high analytical sensitivity even under highly biased relative molecular ratios by balancing the reactivities of each subtype by modifying the concentration of the primers and probes. The multiplex H5/7/9 rRT-PCR assay developed in this study could be a useful tool for large-scale surveillance programs for viral detection as well as subtyping due to its high specificity, sensitivity and robustness in discriminating viruses in mixed infections, and this approach would greatly decrease the time, cost, effort and chance of cross-contamination compared to the conventional method of testing three subtypes by different singleplex rRT-PCR methods in parallel or in series.

The HSP90 inhibitor HVH-2930 exhibits potent efficacy against trastuzumab-resistant HER2-positive breast cancer.

Rationale: Resistance to targeted therapies like trastuzumab remains a critical challenge for HER2-positive breast cancer patients. Despite the progress of several N-terminal HSP90 inhibitors in clinical trials, none have achieved approval for clinical use, primarily due to issues such as induction of the heat shock response (HSR), off-target effects, and unfavorable toxicity profiles. We sought to examine the effects of HVH-2930, a novel C-terminal HSP90 inhibitor, in overcoming trastuzumab resistance. Methods: The effect of HVH-2930 on trastuzumab-sensitive and -resistant cell lines in vitro was evaluated in terms of cell viability, expression of HSP90 client proteins, and impact on cancer stem cells. An in vivo model with trastuzumab-resistant JIMT-1 cells was used to examine the efficacy and toxicity of HVH-2930. Results: HVH-2930 was rationally designed to fit into the ATP-binding pocket interface cavity of the hHSP90 homodimer in the C-terminal domain of HSP90, stabilizing its open conformation and hindering ATP binding. HVH-2930 induces apoptosis without inducing the HSR but by specifically suppressing the HER2 signaling pathway. This occurs with the downregulation of HER2/p95HER2 and disruption of HER2 family member heterodimerization. Attenuation of cancer stem cell (CSC)-like properties was associated with the downregulation of stemness factors such as ALDH1, CD44, Nanog and Oct4. Furthermore, HVH-2930 administration inhibited angiogenesis and tumor growth in trastuzumab-resistant xenograft mice. A synergistic effect was observed when combining HVH-2930 and paclitaxel in JIMT-1 xenografts. Conclusion: Our findings highlight the potent efficacy of HVH-2930 in overcoming trastuzumab resistance in HER2-positive breast cancer. Further investigation is warranted to fully establish its therapeutic potential.

Surveillance and Genetic Analysis of Low-Pathogenicity Avian Influenza Viruses Isolated from Feces of Wild Birds in Mongolia, 2021 to 2023.

The introduction of novel highly pathogenic (HPAI) viruses into Korea has been attributed to recombination events occurring at breeding sites in the Northern Hemisphere. This has increased interest in monitoring and genetically analyzing avian influenza viruses (AIVs) in northern regions, such as Mongolia, which share migratory bird flyways with Korea. AIVs in Mongolia were monitored by analyzing 10,149 fecal samples freshly collected from wild birds from April to October in 2021 to 2023. The prevalence of AIVs in wild birds was 1.01%, with a total of 77 AIVs isolated during these 3 years. These 77 AIVs included hemagglutinin (HA) subtypes H1, H2, H3, H4, H6, H10 and H13 and neuraminidase (NA) subtypes N1, N2, N3, N6, N7 and N8. The most frequently detected subtype combinations were H3N8 (39.0%) and H4N6 (19.5%), although HPAI viruses were not detected. Genetic analysis indicated that theses AIVs isolated from Mongolian samples were closely related to AIVs in wild birds in Korea, including those of Eurasian lineage. These findings indicate the necessity of continuous AIV surveillance and monitoring, as HPAI viruses introduced into Korea may derive from strains in Mongolia.

Biomimetic Self-Propelled Asymmetric Nanomotors for Cascade-Targeted Treatment of Neurological Inflammation.

The precise targeted delivery of therapeutic agents to deep regions of the brain is crucial for the effective treatment of various neurological diseases. However, achieving this goal is challenging due to the presence of the blood‒brain barrier (BBB) and the complex anatomy of the brain. Here, a biomimetic self-propelled nanomotor with cascade targeting capacity is developed for the treatment of neurological inflammatory diseases. The self-propelled nanomotors are designed with biomimetic asymmetric structures with a mesoporous SiO2 head and multiple MnO2 tentacles. Macrophage membrane biomimetic modification endows nanomotors with inflammatory targeting and BBB penetration abilities The MnO2 agents catalyze the degradation of H2O2 into O2, not only by reducing brain inflammation but also by providing the driving force for deep brain penetration. Additionally, the mesoporous SiO2 head is loaded with curcumin, which actively regulates macrophage polarization from the M1 to the M2 phenotype. All in vitro cell, organoid model, and in vivo animal experiments confirmed the effectiveness of the biomimetic self-propelled nanomotors in precise targeting, deep brain penetration, anti-inflammatory, and nervous system function maintenance. Therefore, this study introduces a platform of biomimetic self-propelled nanomotors with inflammation targeting ability and active deep penetration for the treatment of neurological inflammation diseases.

Synergistic oxidation induced by underwater bubbling plasma and diatomite-CoFe2O4 activated peroxymonosulfate for the degradation of ciprofloxacin hydrochloride.

Underwater bubbling plasma (UBP) coupled with diatomite-CoFe2O4 (Dt-CFO) activated peroxymonosulfate (PMS) was proposed for the degradation of ciprofloxacin hydrochloride (CIP) in this work. The catalyst sample of Dt-CFO with large specific surface area, rich active sites and excellent magnetic property was prepared by the hydrothermal method and systematically characterized to investigate its material properties. The combination of UBP and Dt-CFO activated PMS (UBP/Dt-CFO/PMS) showed excellent synergy with the synergistic factor of 1.98, and reached the CIP degradation percentage of 94.7%, which corresponded to the kinetic constant of 0.097 min-1. Dt-CFO with the diatomite content of 30 wt% achieved the best catalytic activity in the reaction system. Higher catalyst and PMS dose, peak voltage, pulse frequency and lower initial CIP concentration were beneficial for CIP removal. The addition of Cl-, HCO3-, SO42- and humic acid suppressed CIP degradation, while NO3- had no effect on CIP removal. The Dt-CFO composite exhibited excellent reusability and low leaching metal amount, demonstrating its good stability. SO4-·, ·OH, ·O2-, 1O2, eaq, O3 and H2O2 were the active species confirmed to be involved in CIP degradation. The redox circles of ≡ Co(Ⅱ)/≡Co(Ⅲ) and ≡ Fe(Ⅱ)/≡Fe(Ⅲ) on Dt-CFO surface and the plasma-induced physicochemical effects dominated PMS activation. The decomposition process of CIP was explored through fluorescence spectra. Three degradation pathways were inferred, and the toxicity analysis showed the toxicity of CIP solution weakened after discharge treatment.

Case report: Management of recurrent pupillary optic capture with sutureless surgical technique using 7-0 polypropylene flange.

Background: To report a novel surgical technique for recurrent pupillary optic capture after flanged intraocular lens (IOL) fixation. Methods: In this retrospective case series, we detail our use of two parallel 7-0 polypropylene sutures passed between the iris plane and the optic of scleral-fixated IOL to address pupillary optic capture. Flanges were created using ophthalmic cautery to secure it to the sclera without suture. Results: Two eyes with pupillary optic capture underwent a sutureless surgical technique using 7-0 polypropylene flanges. No recurrences of pupillary optic capture were observed during the 1-year follow-up. Conclusion: Our sutureless surgical technique using a 7-0 polypropylene flange was an effective, efficient, and less invasive approach for treating recurrent pupillary optic capture.

Repositioned versus exchanged flanged intraocular lens fixation for intraocular lens dislocation.

This study aimed to compare the outcomes of flanged intraocular lens (IOL) fixation with new IOL exchange after dislocated IOL removal and repositioned dislocated IOL in patients with IOL dislocation. Eighty-nine eyes that underwent flanged IOL fixation were retrospectively included, with 51 eyes in the exchanged IOL group and 38 eyes in the repositioned IOL group. In both groups, best-corrected visual acuity (BCVA) improved at 1, 3, 6, and 12 months postoperatively and did not differ between the two groups at any of these time points. However, at 1 week postoperatively, BCVA in the repositioned IOL group improved compared with baseline, whereas that in the exchanged IOL group did not. Moreover, there were lesser changes in the corneal endothelial cell density (ECD) and corneal astigmatism in the repositioned IOL group than in the exchanged IOL group. The IOL positions, including IOL tilt and IOL decentration, were not different between the groups. Flanged IOL fixation with new IOL exchange and with repositioned dislocated IOL for patients with IOL dislocation had similar visual outcomes and IOL position. However, the latter had a smaller corneal ECD decrease and astigmatic change. This technique was effective in treating IOL dislocation while minimizing corneal injury.

Enhancing the Spermidine Synthase-Based Polyamine Biosynthetic Pathway to Boost Rapid Growth in Marine Diatom Phaeodactylum tricornutum.

Diatoms, efficient carbon capture organisms, contribute to 20% of global carbon fixation and 40% of ocean primary productivity, garnering significant attention to their growth. Despite their significance, the synthesis mechanism of polyamines (PAs), especially spermidine (Spd), which are crucial for growth in various organisms, remains unexplored in diatoms. This study reveals the vital role of Spd, synthesized through the spermidine synthase (SDS)-based pathway, in the growth of the diatom Phaeodactylum tricornutum. PtSDS1 and PtSDS2 in the P. tricornutum genome were confirmed as SDS enzymes through enzyme-substrate selectivity assays. Their distinct activities are governed primarily by the Y79 active site. Overexpression of a singular gene revealed that PtSDS1, PtSDS2, and PtSAMDC from the SDS-based synthesis pathway are all situated in the cytoplasm, with no significant impact on PA content or diatom growth. Co-overexpression of PtSDS1 and PtSAMDC proved essential for elevating Spd levels, indicating multifactorial regulation. Elevated Spd content promotes diatom growth, providing a foundation for exploring PA functions and regulation in diatoms.

Programmed microalgae-gel promotes chronic wound healing in diabetes.

Chronic diabetic wounds are at lifelong risk of developing diabetic foot ulcers owing to severe hypoxia, excessive reactive oxygen species (ROS), a complex inflammatory microenvironment, and the potential for bacterial infection. Here we develop a programmed treatment strategy employing live Haematococcus (HEA). By modulating light intensity, HEA can be programmed to perform a variety of functions, such as antibacterial activity, oxygen supply, ROS scavenging, and immune regulation, suggesting its potential for use in programmed therapy. Under high light intensity (658 nm, 0.5 W/cm2), green HEA (GHEA) with efficient photothermal conversion mediate wound surface disinfection. By decreasing the light intensity (658 nm, 0.1 W/cm2), the photosynthetic system of GHEA can continuously produce oxygen, effectively resolving the problems of hypoxia and promoting vascular regeneration. Continuous light irradiation induces astaxanthin (AST) accumulation in HEA cells, resulting in a gradual transformation from a green to red hue (RHEA). RHEA effectively scavenges excess ROS, enhances the expression of intracellular antioxidant enzymes, and directs polarization to M2 macrophages by secreting AST vesicles via exosomes. The living HEA hydrogel can sterilize and enhance cell proliferation and migration and promote neoangiogenesis, which could improve infected diabetic wound healing in female mice.

Dual-functional heterogeneous Fenton catalyst Cu/Ti co-doped Fe3O4@FeOOH for cyanide-containing wastewater treatment: Preparation, performance and mechanism.

The dual-functional heterogeneous Fenton catalyst Cu/Ti co-doped iron-based Fenton catalyst (Cu/Ti -Fe3O4@FeOOH, FCT) were successfully prepared by precipitation oxidation method and characterized by XRD, XPS and XAFS. The prepared Cu/Ti co-doped Fe3O4@FeOOH nanoparticles consisted of goethite nanorods and magnetite rod octahedral particles, with Cu and Ti replacing Fe in the catalyst crystal structure, leading to the formation of the goethite structure. The heterogeneous Fenton catalyst FCT exhibited excellent degradation activity for cyanide in wastewater and showed different reaction mechanisms at varying pH levels. When treating 100 mL of 12 mg L-1 NaCN solution, complete degradation occurred within 40 min at 30 °C and pH ranging from 6.5 to 12.5 without external energy. Compared to Fe3O4, FCT shows superior degradation activity for cyanide. The surface Cu(Ⅰ) facilitated the electron transfer and significantly improved the catalytic activity of the catalyst. Additionally, the magnetic properties of the Ti-doped catalyst samples were greatly enhanced compared to the Cu@FeOOH catalyst doped with Cu, making them favorable for recycling and reuse. FCT maintains 100% degradation of cyanogen after three cycles, indicating its excellent stability. Furthermore, electron spin resonance spectroscopy, free radical quenching experiments and fluorescence probe techniques using terephthalic acid (TA) and benzoic acid (BA) confirmed that the presence of •OH and FeⅣ=O reactive species was responsible for the catalysts exhibiting different mechanisms at different pH conditions. Compared with other heterogeneous Fenton catalysts, FCT exhibits intentional degradation activity for cyanide-containing wastewater under different acid-base conditions, which greatly broadened the pH range of the heterogeneous Fenton reaction.

Oxygen Reduction Kinetics of Fe-N-C Single Atom Catalysts Boosted by Pyridinic N Vacancy for Temperature-Adaptive Zn-Air Batteries.

The design of temperature-adaptive Zn-air batteries (ZABs) with long life spans and high energy efficiencies is challenging owing to sluggish oxygen reduction reaction (ORR) kinetics and an unstable Zn/electrolyte interface. Herein, a quasi-solid-state ZAB is designed by combining atomically dispersed Fe-N-C catalysts containing pyridinic N vacancies (FeNC-VN) with a polarized organo-hydrogel electrolyte. First-principles calculation predicts that adjacent VN sites effectively enhance the covalency of Fe-Nx moieties and moderately weaken *OH binding energies, significantly boosting the ORR kinetics and stability. In situ Raman spectra reveal the dynamic evolution of *O2- and *OOH on the FeNC-VN cathode in the aqueous ZAB, proving that the 4e- associative mechanism is dominant. Moreover, the ethylene glycol-modulated organo-hydrogel electrolyte forms a zincophilic protective layer on the Zn anode surface and tailors the [Zn(H2O)6]2+ solvation sheath, effectively guiding epitaxial deposition of Zn2+ on the Zn (002) plane and suppressing side reactions. The assembled quasi-solid-state ZAB demonstrates a long life span of over 1076 h at 2 mA cm-2 at -20 °C, outperforming most reported ZABs.

Anisotropically Conductive Hydrogels with Directionally Aligned PEDOT:PSS in a PVA Matrix.

Electrical anisotropy, which is characterized by the efficient transmission of electrical signals in specific directions, is prevalent in both natural and engineered systems. However, traditional anisotropically conductive materials are often rigid and dry, thus limiting their utility in applications aiming for the seamless integration of various technologies with biological tissues. In the present study, we introduce a method for precisely controlling the microstructures of conductive and insulating polymers to create highly anisotropically conductive composite hydrogels. Our methodology involves combining aligned poly(vinyl alcohol) microfibrils, infused poly(3,4-ethylenedioxythiophene) polystyrenesulfonate, and sodium citrate precipitation to form dense, aligned conductive paths. This significantly enhances the electrical conductivity anisotropy (σ∥/σ⊥ ≈ 60.8) within these composite hydrogels.