Three-dimensional atomic structure and local chemical order of medium- and high-entropy nanoalloys.

Medium- and high-entropy alloys (M/HEAs) mix several principal elements with near-equiatomic composition and represent a model-shift strategy for designing previously unknown materials in metallurgy1-8, catalysis9-14 and other fields15-18. One of the core hypotheses of M/HEAs is lattice distortion5,19,20, which has been investigated by different numerical and experimental techniques21-26. However, determining the three-dimensional (3D) lattice distortion in M/HEAs remains a challenge. Moreover, the presumed random elemental mixing in M/HEAs has been questioned by X-ray and neutron studies27, atomistic simulations28-30, energy dispersive spectroscopy31,32 and electron diffraction33,34, which suggest the existence of local chemical order in M/HEAs. However, direct experimental observation of the 3D local chemical order has been difficult because energy dispersive spectroscopy integrates the composition of atomic columns along the zone axes7,32,34 and diffuse electron reflections may originate from planar defects instead of local chemical order35. Here we determine the 3D atomic positions of M/HEA nanoparticles using atomic electron tomography36 and quantitatively characterize the local lattice distortion, strain tensor, twin boundaries, dislocation cores and chemical short-range order (CSRO). We find that the high-entropy alloys have larger local lattice distortion and more heterogeneous strain than the medium-entropy alloys and that strain is correlated to CSRO. We also observe CSRO-mediated twinning in the medium-entropy alloys, that is, twinning occurs in energetically unfavoured CSRO regions but not in energetically favoured CSRO ones, which represents, to our knowledge, the first experimental observation of correlating local chemical order with structural defects in any material. We expect that this work will not only expand our fundamental understanding of this important class of materials but also provide the foundation for tailoring M/HEA properties through engineering lattice distortion and local chemical order.

microRNA-induced translational control of antiviral immunity by the cap-binding protein 4EHP.

Type I interferons (IFNs) are critical cytokines in the host defense against invading pathogens. Sustained production of IFNs, however, is detrimental to the host, as it provokes autoimmune diseases. Thus, the expression of IFNs is tightly controlled. We report that the mRNA 5' cap-binding protein 4EHP plays a key role in regulating type I IFN concomitant with controlling virus replication, both in vitro and in vivo. Mechanistically, 4EHP suppresses IFN-ß production by effecting the miR-34a-induced translational silencing of Ifnb1 mRNA. miR-34a is upregulated by both RNA virus infection and IFN-ß induction, prompting a negative feedback regulatory mechanism that represses IFN-ß expression via 4EHP. These findings demonstrate the direct involvement of 4EHP in virus-induced host response, underscoring a critical translational silencing mechanism mediated by 4EHP and miR-34a to impede sustained IFN production. This study highlights an intrinsic regulatory function for miRNA and the translation machinery in maintaining host homeostasis.

The Gß-like protein Bcgbl1 regulates development and pathogenicity of the gray mold Botrytis cinerea via modulating two MAP kinase signaling pathways.

The fungal Gß-like protein has been reported to be involved in a variety of biological processes, such as mycelial growth, differentiation, conidiation, stress responses and infection. However, molecular mechanisms of the Gß-like protein in regulating fungal development and pathogenicity are largely unknown. Here, we show that the Gß-like protein gene Bcgbl1 in the gray mold fungus Botrytis cinerea plays a pivotal role in development and pathogenicity by regulating the mitogen-activated protein (MAP) kinases signaling pathways. The Bcgbl1 deletion mutants were defective in mycelial growth, sclerotial formation, conidiation, macroconidial morphogenesis, plant adhesion, and formation of infection cushions and appressorium-like structures, resulting in a complete loss of pathogenicity. Bcgbl1 interacted with BcSte50, the adapter protein of the cascade of MAP kinase (MAPK). Bcgbl1 mutants had reduced phosphorylation levels of two MAPKs, namely Bmp1 and Bmp3, thereby reducing infection. However, deletion of Bcgbl1 did not affect the intracellular cAMP level, and exogenous cAMP could not restore the defects. Moreover, Bcgbl1 mutants exhibited defects in cell wall integrity and oxidative stress tolerance. Transcriptional profiling revealed that Bcgbl1 plays a global role in regulation of gene expression upon hydrophobic surface induction. We further uncovered that three target genes encoding the hydrophobic surface binding proteins (HsbAs) contributed to the adhesion and virulence of B. cinerea. Overall, these findings suggest that Bcgbl1 had multiple functions and provided new insights for deciphering the Bcgbl1-mediated network for regulating development and pathogenicity of B. cinerea.

ELF4 is critical for induction of type I interferon and the host antiviral response.

Induction of type I interferon is a central event of innate immunity, essential for host defense. Here we report that the transcription factor ELF4 is induced by type I interferon and upregulates interferon expression in a feed-forward loop. ELF4 deficiency leads to reduced interferon production, resulting in enhanced susceptibility to West Nile virus encephalitis in mice. After viral infection, ELF4 is recruited by STING, interacts with and is activated by the MAVS-TBK1 complex, and translocates into the nucleus to bind interferon promoters. Cooperative binding with ELF4 increases the binding affinity of interferon regulatory factors IRF3 and IRF7, which is mediated by EICE elements. Thus, in addition to identifying a regulator of innate immune signaling, we uncovered a role for EICE elements in interferon transactivation.

Mitochondria-derived peptide is an effective target for treating streptozotocin induced painful diabetic neuropathy through induction of activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1alpha -mediated mitochondrial biogenesis.

Painful Diabetic Neuropathy (PDN) is a common diabetes complication that frequently causes severe hyperalgesia and allodynia and presents treatment challenges. Mitochondrial-derived peptide (MOTS-c), a novel mitochondrial-derived peptide, has been shown to regulate glucose metabolism, insulin sensitivity, and inflammatory responses. This study aimed to evaluate the effects of MOTS-c in streptozocin (STZ)-induced PDN model and investigate the putative underlying mechanisms. We found that endogenous MOTS-c levels in plasma and spinal dorsal horn were significantly lower in STZ-treated mice than in control animals. Accordingly, MOTS-c treatment significantly improves STZ-induced weight loss, elevation of blood glucose, mechanical allodynia, and thermal hyperalgesia; however, these effects were blocked by dorsomorphin, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor. In addition, MOTS-c treatment significantly enhanced AMPKα1/2 phosphorylation and PGC-1α expression in the lumbar spinal cord of PDN mice. Mechanistic studies indicated that MOTS-c significantly restored mitochondrial biogenesis, inhibited microglia activation, and decreased the production of pro-inflammatory factors, which contributed to the alleviation of pain. Moreover, MOTS-c decreased STZ-induced pain hypersensitivity in PDN mice by activating AMPK/PGC-1α signaling pathway. This provides the pharmacological and biological evidence for developing mitochondrial peptide-based therapeutic agents for PDN.

Nucleolin lactylation contributes to intrahepatic cholangiocarcinoma pathogenesis via RNA splicing regulation of MADD.

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a fatal malignancy of the biliary system. The lack of a detailed understanding of oncogenic signaling or global gene expression alterations has impeded clinical iCCA diagnosis and therapy. The role of protein lactylation, a newly unraveled post-translational modification that orchestrates gene expression, remains largely elusive in the pathogenesis of iCCA. METHODS: Proteomics analysis of clinical iCCA specimens and adjacent tissues was performed to screen for proteins aberrantly lactylated in iCCA. Mass spectrometry, macromolecule interaction and cell behavioral studies were employed to identify the specific lactylation sites on the candidate protein(s) and to decipher the downstream mechanisms responsible for iCCA development, which were subsequently validated using a xenograft tumor model and clinical samples. RESULTS: Nucleolin (NCL), the most abundant RNA-binding protein in the nucleolus, was identified as a functional lactylation target that correlates with iCCA occurrence and progression. NCL was lactylated predominantly at lysine 477 by the acyltransferase P300 in response to a hyperactivity of glycolysis, and promoted the proliferation and invasion of iCCA cells. Mechanistically, lactylated NCL bound to the primary transcript of MAP kinase-activating death domain protein (MADD) and led to efficient translation of MADD by circumventing alternative splicing that generates a premature termination codon. NCL lactylation, MADD translation and subsequent ERK activation promoted xenograft tumor growth and were associated with overall survival in patients with iCCA. CONCLUSION: NCL is lactylated to upregulate MADD through an RNA splicing-dependent mechanism, which potentiates iCCA pathogenesis via the MAPK pathway. Our findings reveal a novel link between metabolic reprogramming and canonical tumor-initiating events, and uncover biomarkers that can potentially be used for prognostic evaluation or targeted treatment of iCCA. IMPACT AND IMPLICATIONS: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive liver malignancy with largely uncharacterized pathogenetic mechanisms. Herein, we demonstrated that glycolysis promotes P300-catalyzed lactylation of nucleolin, which upregulates MAP kinase-activating death domain protein (MADD) through precise mRNA splicing and activates ERK signaling to drive iCCA development. These findings unravel a novel link between metabolic rewiring and canonical oncogenic pathways, and reveal new biomarkers for prognostic assessment and targeting of clinical iCCA.

Use of Interfacial Interactions and Complexation of Carbon Dots to Construct Ultra-Robust and Efficient Photothermal Film From Micro-Carbonized Polysaccharides.

Solar energy conversion technologies, particularly solar-driven photothermal conversion, are both clean and manageable. Although much progress has been made in designing solar-driven photothermal materials, significant challenges remain, not least the photobleaching of organic dyes. To tackle these issues, micro-carbonized polysaccharide chains, with carbon dots (CDs) suspended from the chains, are conceived, just like grapes or tomatoes hanging from a vine. Carbonization of sodium carboxymethyl cellulose (CMC) produces just such a structure (termed CMC-g-CDs), which is used to produce an ultra-stable, robust, and efficient solar-thermal film by interfacial interactions within the CMC-g-CDs. The introduction of the CDs into the matrix of the photothermal material effectively avoided the problem of photobleaching. Manipulating the interfacial interactions (such as electrostatic interactions, van der Waals interactions, π-π stacking, and hydrogen bonding) between the CDs and the polymer chains markedly enhances the mechanical properties of the photothermal film. The CMC-g-CDs are complexed with Fe3+ to eliminate leakage of the photothermal reagent from the matrix and to solve the problem of poor water resistance. The resulting film (CMC-g-CDs-Fe) has excellent prospects for practical application as a photothermal film.

Ultra-Thin Hydrogen-Organic-Framework (HOF) Nanosheets for Ultra-Stable Alkali Ions Battery Storage.

Organic frameworks-based batteries with excellent physicochemical stability and long-term high capacity will definitely reduce the cost, carbon emissions, and metal consumption and contamination. Here, an ultra-stable and ultra-thin perylene-dicyandiamide-based hydrogen organic framework (HOF) nanosheet (P-DCD) of ≈3.5 nm in thickness is developed. When applied in the cathode, the P-DCD exhibits exceptional long-term capacity retention for alkali-ion batteries (AIBs). Strikingly, for lithium-ion batteries (LIBs), at current of 2 A g-1, the large reversible capacity of 108 mA h g-1 shows no attenuation within 5 000 cycles. For sodium-ion batteries (SIBs), the related capacity retains 91.7% within 10 000 cycles compared to the initial state, significantly much more stable than conventional organic materials reported previously. Mechanism studies through ex situ and in situ experiments and theoretical density functional theory (DFT) calculations reveal that the impressive long-term performance retention originates from the large electron delocalization, fast ion diffusion, and physicochemical stability within the ultra-thin 2D P-DCD, featuring π-π and hydrogen bonding stacking, nitrogen-rich units, and low impedance. The advantageous features demonstrate that rationally designed stable and effective organic frameworks pave the way to utilizing complete organic materials for developing next-generation low-cost and highly stable energy storage batteries.

Enhanced Light Absorption and Photo-Generated Charge Separation Efficiency for Boosting Photocatalytic H2 Evolution through TiO2 Quantum Dots with N-Doping and Concomitant Oxygen Vacancy.

Low-range light absorption and rapid recombination of photo-generated charge carriers have prevented the occurrence of effective and applicable photocatalysis for decades. Quantum dots (QDs) offer a solution due to their size-controlled photon properties and charge separation capabilities. Herein, well-dispersed interstitial nitrogen-doped TiO2 QDs with stable oxygen vacancies (N-TiO2-x-VO) are fabricated by using a low-temperature, annealing-assisted hydrothermal method. Remarkably, electrostatic repulsion prevented aggregation arising from negative charges accumulated in situ on the surface of N-TiO2-x-VO, enabling complete solar spectrum utilization (200-800 nm) with a 2.5 eV bandgap. Enhanced UV-vis photocatalytic H2 evolution rate (HER) reached 2757 µmol g-1 h-1, 41.6 times higher than commercial TiO2 (66 µmol g-1 h-1). Strikingly, under visible light, HER rate was 189 µmol g-1 h-1. Experimental and simulated studies of mechanisms reveal that VO can serve as an electron reservoir of photo-generated charge carriers on N-doped active sites, and consequently, enhance the separation rate of exciton pairs. Moreover, the negative free energy (-0.35 V) indicates more favorable thermodynamics for HER as compared with bulk TiO2 (0.66 V). This research work paves a new way of developing efficient photocatalytic strategies of HER that are applicable in the sustainable carbon-zero energy supply.

SERINC5 restricts influenza virus infectivity.

SERINC5 is a multi-span transmembrane protein that is incorporated into HIV-1 particles in producing cells and inhibits HIV-1 entry. Multiple retroviruses like HIV-1, equine infectious anemia virus and murine leukemia virus are subject to SERINC5 inhibition, while HIV-1 pseudotyped with envelope glycoproteins of vesicular stomatitis virus and Ebola virus are resistant to SERINC5. The antiviral spectrum and the underlying mechanisms of SERINC5 restriction are not completely understood. Here we show that SERINC5 inhibits influenza A virus infection by targeting virus-cell membrane fusion at an early step of infection. Further results show that different influenza hemagglutinin (HA) subtypes exhibit diverse sensitivities to SERINC5 restriction. Analysis of the amino acid sequences of influenza HA1 strains indicates that HA glycosylation sites correlate with the sensitivity of influenza HA to SERINC5, and the inhibitory effect of SERINC5 was lost when certain HA glycosylation sites were mutated. Our study not only expands the antiviral spectrum of SERINC5, but also reveals the role of viral envelope glycosylation in resisting SERINC5 restriction.

Inhibitor of cardiolipin biosynthesis-related enzyme MoGep4 confers broad-spectrum anti-fungal activity.

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

Function analysis and characterisation of a novel chitinase, MdCht9, in Musca domestica.

Insect chitinases have been proposed as potential targets for pest control. In this work, a novel group IV chitinase gene, MdCht9, from Musca domestica was found to have multiple functions in the physiological activity, including chitin regulation, development and antifungal immunity. The MdCht9 gene was cloned and sequenced, its phylogeny was analysed and its expression was determined in normal and 20E treated larvae. Subsequently, RNA interference (RNAi)-mediated MdCht9 knockdown was performed, followed by biochemical assays, morphological observations and transcriptome analysis. Finally, the recombinant protein MdCht9 (rMdCht9) was purified and tested for anti-microbial activity and enzyme characteristics. The results showed that MdCht9 consists of three domains, highly expressed in a larval salivary gland. RNAi silencing of MdCht9 resulted in significant down-regulation of chitin content and expression of 15 chitin-binding protein (CBP) genes, implying a new insight that MdCht9 might regulate chitin content by influencing the expression of CBPs. In addition, more than half of the lethality and partial wing deformity appeared due to the dsMdCht9 treatment. In addition, the rMdCht9 exhibited anti-microbial activity towards Candida albicans (fungus) but not towards Escherichia coli (G-) or Staphylococcus aureus (G+). Our work expands on previous studies of chitinase while providing a potential target for pest management.

Electrophysiological characteristics and catheter ablation of ventricular arrhythmias arising from the superior septal left ventricle.

BACKGROUND AND AIMS: Electrophysiological characteristics and radiofrequency catheter ablation (RFCA) of premature ventricular contractions (PVCs) originating from the superior septal left ventricle (SSLV) have not yet been fully characterized. METHODS AND RESULTS: This study included 247 patients who underwent RFCA for PVCs arising from the ventricular outflow tract between February 2020 and August 2022. The successful ablation site was on the SSLV in 37 of the 247 patients. In 12 (32.4%) of those 37 patients, a low amplitude and high frequency spiky potential (SP) was recognized. Five patients showed a narrow QRS duration (86.8 ± 4.6 ms), with a discrete SP observed in PVCs and sinus rhythm, which showed an isoelectric line with the ventricular electrogram at the earliest activation site. Seven patients showed a wide QRS duration (131.6 ± 4.5 ms), with SP observed in PVCs without an isoelectric line with the ventricular electrogram. RFCA was successful at the site of the earliest SP in all 12 patients. The time from SP onset at the successful ablation site to the QRS onset (local activation time) was 30 ± 12 ms, which differed significantly from that for the remaining 25 patients withoutSP(22.1 ± 7.1 ms, P < 0.05). CONCLUSIONS: SPs were recorded in 12 (32.4%) of the 37 patients with PVCs originating from the SSLV. The morphology of the PVCs may show a narrow or wide QRS duration and the target site for successful ablation should be identified by the earliest SP.

Structure and phase transitions in niobium and tantalum derived nanoscale transition metal perovskites, Ba(Ti,MV)O3, M=Nb,Ta.

The prospect of creating ferroelectric or high permittivity nanomaterials provides motivation for investigating complex transition metal oxides of the form Ba(Ti, MV)O3, where M = Nb or Ta. Solid state processing typically produces mixtures of crystalline phases, rarely beyond minimally doped Nb/Ta. Using a modified sol-gel method, we prepared single phase nanocrystals of Ba(Ti, M)O3. Compositional and elemental analysis puts the empirical formulas close to BaTi0.5Nb0.5O3-δ and BaTi0.5Ta0.5O3-δ. For both materials, a reversible temperature dependent phase transition (non-centrosymmetric to symmetric) is observed in the Raman spectrum in the region 533-583 K (260-310 °C); for Ba(Ti, Nb)O3, the onset is at 543 K (270 °C); and for Ba(Ti, Ta)O3, the onset is at 533 K (260 °C), which are comparable with 390-393 K (117-120 °C) for bulk BaTiO3. The crystal structure was resolved by examination of the powder x-ray diffraction and atomic pair distribution function (PDF) analysis of synchrotron total scattering data. It was postulated whether the structure adopted at the nanoscale was single or double perovskite. Double perovskites (A2B'B″O6) are characterized by the type and extent of cation ordering, which gives rise to higher symmetry crystal structures. PDF analysis was used to examine all likely candidate structures and to look for evidence of higher symmetry. The feasible phase space that evolves includes the ordered double perovskite structure Ba2(Ti, MV)O6 (M = Nb, Ta) Fm-3m, a disordered cubic structure, as a suitable high temperature analog, Ba(Ti, MV)O3Pm-3m, and an orthorhombic Ba(Ti, MV)O3Amm2, a room temperature structure that presents an unusually high level of lattice displacement, possibly due to octahedral tilting, and indication of a highly polarized crystal.

Fasciculoventricular accessory pathway masked extensive atrioventricular conduction system disease in a patient with PRKAG2 syndrome.

A 23-year-old male with a history of ventricular pre-excitation and atrial flutter presented for evaluation after recurrent syncope. The possible mechanism of syncope erroneously attributed to pre-excited atrial flutter with fast heart rates in the first hospitalization. The patient was found to have advanced heart block and PRKAG2 genetic mutation in the second hospitalization. The genetic findings and clinical features are consistent with PRKAG2 syndrome (PS). PS is a rare, autosomal dominant inherited disease, characterized by ventricular pre-excitation, supraventricular tachycardia, and cardiac hypertrophy. It is frequently followed by atrial-fibrillation-induced ventricular fibrillation and advanced heart blocks. An accurate differential diagnosis of syncope is important because of the different arrhythmic features and clinical course of PS.

The effectiveness and safety of Rivaroxaban and Edoxaban in the treatment of lower extremity deep vein thrombosis.

INTRODUCTION: Deep vein thrombosis (DVT) is a medical condition characterized by forming a blood clot, or thrombus, in one of the deep veins, typically in the legs. It is a type of venous thromboembolism (VTE), which refers to the formation of blood clots in the veins. It is caused by Virchow's triad (stasis, hypercoagulation, and endothelial injury). OBJECTIVE: Our main objective is to explore the effectiveness and safety of Rivaroxaban and Edoxaban in treating lower extremity deep vein thrombosis. METHODS: We conducted a retrospective study involving 406 patients subjected to DVT treatment using DOACs (Edoxaban and Rivaroxaban) at our hospital. We recruited adult patients (18 years and above) diagnosed with lower extremity deep vein thrombosis and received treatment with either Rivaroxaban or Edoxaban as the primary anticoagulant therapy for DVT. We excluded patients who received treatment with other anticoagulant medications (warfarin heparin) as the primary therapy for DVT. RESULTS: The groups showed statistically significant differences in red blood cell count and haemoglobin levels, with the Edoxaban group having high values. However, the two groups observed no statistically significant differences in creatinine clearance, white blood cell count, platelet count, C-reactive protein, and D-dimer levels. The difference in the incidence of PE between the two groups was statistically significant (P value < 0.001). The Edoxaban group had fewer PE patients than the rivaroxaban group. The reduction in recurrent thrombosis was significantly higher in the rivaroxaban group compared to the Edoxaban group. There were no significant differences in the major bleeding at various sites across the two treatment groups (p > 0.05). CONCLUSION: Rivaroxaban's pharmacokinetic profile includes rapid absorption and a relatively short half-life. It means that once administered, Rivaroxaban quickly reaches its peak concentration in the blood and is subsequently eliminated from the body within a relatively short period. Edoxaban's pharmacokinetic profile may include slower absorption and a longer half-life than Rivaroxaban. It can result in a slower rate of achieving peak concentration and a more prolonged presence in the bloodstream. These results emphasize the need for careful consideration of anticoagulant therapy in patients with underlying cancer and underscore the importance of managing risks while providing adequate anticoagulation to prevent thrombotic events.

Predictive value of soluble CD40L combined with APACHE II score in elderly patients with sepsis in the emergency department.

BACKGROUND: The prognostic performance of soluble CD40L (sCD40L) for illness severity in infectious diseases is rarely reported. We investigated the ability of sCD40L combined with Acute Physiology and Chronic Health Evaluation II (APACHE II) score to evaluate mortality in septic patients in the emergency department(ED). METHODS: We enrolled 222 septic patients in the ED of Beijing Chao-Yang Hospital from October 2020 to April 2021. Their serum sCD40L, PCT, lactate (Lac), Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score were used to predict the prognosis of septic patients in terms of 28-day mortality. Serum sCD40L was detected by Human XL Cytokine Luminex. Logistic regression analysis and receiver operating characteristic (ROC) curves were used to assess the prognostic value of the variables. RESULTS: One hundred ninety-five patients met the inclusion criteria, divided into survival group (55 cases) and non-survival group (140 cases). sCD40L, PCT, Lac, SOFA and APACHE II score were found to independently predict 28-day mortality (P < 0.05). The AUC values of sCD40L, PCT, Lac, SOFA and APACHE II score were 0.662,0.727,0.704, 0.719 and 0.716, respectively. There was no difference in the diagnostic value of sCD40L compared with the PCT, Lac, SOFA score or APACHE II score (Z1 = 1.19, P = 0.234; Z2 = 0.77, P = 0.441; Z3 = 1.05, P = 0.294; Z4 = 0.97, P = 0.332). However, the combined evaluation of sCD40L + APACHE II (AUC:0.772, Z = 2.10, P = 0.036) was much better than sCD40L alone in predicting 28-day mortality. CONCLUSION: The predictive value of sCD40L + APACHE II is better than sCD40L alone for 28-day mortality. sCD40L combined with APACHE II score is valuable for predicting 28-day mortality in elderly patients with sepsis.

Intraoperative radiographic analysis and adjustment of the optimal position of plate in high tibial osteotomy.

BACKGROUND: When high tibial osteotomy is performed for genu varus deformity, it is not easy to determine the accurate placement of the plate. PURPOSE: To determine a simple way to assess the position of the plate, to provide more effective mechanical support and to reduce the risk of implant rupture and vascular injury. MATERIAL AND METHODS: Two human anatomical marks, the patellar ligament and semimembranosus, were connected and divided into four parts to identify points Ⅰ, Ⅱ, and Ⅲ. These points determined the areas for Tomofix placement: anterior, anterolateral, and lateral. Simulated internal fixation placed hole B of Tomofix at points Ⅰ (anterior), Ⅱ (anterolateral), and Ⅲ (lateral). We analyzed the pointing direction of the locking screws in Tomofix holes on MRI to assess potential injury risk to the popliteal neurovascular bundle. RESULTS: In the X-ray: holes B and C appeared as the plate in the anterior, only hole C appeared as the plate in the anterolateral, and none of the holes appeared as the plate in the lateral. In the general view of the sawbones, the screw pointed towards the popliteal neurovascular bundle when the plate was in the anterior. CONCLUSION: If a small number of holes on the plate is visible under fluoroscopy, then several lateral positions of the plate can be obtained; the direction of the screw tunnel tends to deviate from the popliteal neurovascular bundle with the posterior position of the plate.

MOTS-c is an effective target for treating cancer-induced bone pain through the induction of AMPK-mediated mitochondrial biogenesis.

Bone cancer pain (BCP), due to cancer bone metastasis and bone destruction, is a common symptom of tumors, including breast, prostate, and lung tumors. Patients often experience severe pain without effective treatment. Here, using a mouse model of bone cancer, we report that MOTS-c, a novel mitochondrial-derived peptide, confers remarkable protection against cancer pain and bone destruction. Briefly, we find that the plasma level of endogenous MOTS-c is significantly lower in the BCP group than in the sham group. Accordingly, intraperitoneal administration of MOTS-c robustly attenuates bone cancer-induced pain. These effects are blocked by compound C, an AMPK inhibitor. Furthermore, MOTS-c treatment significantly enhances AMPKα 1/2 phosphorylation. Interestingly, mechanical studies indicate that at the spinal cord level, MOTS-c relieves pain by restoring mitochondrial biogenesis, suppressing microglial activation, and decreasing the production of inflammatory factors, which directly contribute to neuronal modulation. However, in the periphery, MOTS-c protects against local bone destruction by modulating osteoclast and immune cell function in the tumor microenvironment, providing long-term relief from cancer pain. Additionally, we find that chronic administration of MOTS-c has little effect on liver, renal, lipid or cardiac function in mice. In conclusion, MOTS-c improves BCP through peripheral and central synergistic effects on nociceptors, immune cells, and osteoclasts, providing a pharmacological and biological rationale for the development of mitochondrial peptide-based therapeutic agents for cancer-induced pain.

Association analysis of the sorting nexin 29 (SNX29) gene copy number variations with growth traits in Diannan small-ear (DSE) pigs.

SNX29 is a potential functional gene associated with meat production traits. Previous studies have shown that SNX29 copy number variation (CNV) could be implicated with phenotype in goats. However, in Diannan small-ear (DSE) pigs, the genetic impact of SNX29 CNV on growth traits remains unclear. Therefore, this study investigated the associations between SNX29 CNVs (CNV10810 and CNV10811) and growth traits in 415 DSE pigs. The results revealed that the CNV10810 mutation was significantly associated with backfat thickness in DSE pigs at 12 and 15 months old (P < 0.05), while the CNV10811 mutation had significant effects on various growth traits at 6 and 12 months old, particularly for body weight, body height, back height and backfat thickness (P < 0.05 or P < 0.001). In conclusion, our results confirm that SNX29 CNV plays a role in regulating growth and development in pigs, thus suggesting its potential application for pig breeding programmes.