Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade.

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor efficacy. Targeted radionuclide therapy delivers radiation directly to tumor sites. LNC1004 is a fibroblast activation protein (FAP)-targeting radiopharmaceutical, conjugated with the albumin binder Evans Blue, which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical studies. Herein, we demonstrate that 68Ga/177Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor xenografts. Radionuclide therapy with 177Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor cells. The combination of 177Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice, with mice showing 100% tumor rejection upon rechallenge. Immunohistochemistry, single-cell RNA sequencing (scRNA-seq), and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication, CD8+ T-cell activation and expansion, M1 macrophage counts, antitumor activity of neutrophils, and T-cell receptor diversity. A preliminary clinical study demonstrated that 177Lu-LNC1004 was well-tolerated and effective in patients with refractory cancers. Further, scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade treatment. This was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell inactivation. In conclusion, our data supported the efficacy of immunotherapy combined with 177Lu-LNC1004 for cancer patients with FAP-positive tumors.

Effect of extracorporeal shock wave therapy for rotator cuff injury: Protocol for a systematic review and meta-analysis.

BACKGROUND: Rotator cuff injury (RCI) is a common musculoskeletal ailment and a major cause of shoulder pain and limited functionality. The ensuing pain and restricted movement significantly impact overall quality of life. This study aims to systematically review the effects of extracorporeal shock wave therapy (ESWT) on RCI. METHODS: This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. A literature search, spanning inception to November 1, 2023, will include databases such as PubMed, Web of Science, the Cochrane Library, Scopus, MEDLINE, EMBASE, EBSCO, and China National Knowledge Infrastructure (CNKI) to identify ESWT studies for RCI treatment. Excluding retrospectives, bias risk will be assessed with the Cochrane tool. Two researchers will independently screen, extract data, and evaluate bias risk. Revman 5.3 software will be used for data analysis. RESULTS: This study aims to objectively and comprehensively evaluate the effectiveness and safety of randomized controlled trials of ESWT in the treatment of RCI, and analyze in detail the effect of ESWT in the treatment of RCI. Results will be analyzed using the Pain Visual Analogue Scale (VAS), Constant-Murley score, University of California Los Angeles score (UCLA), and American Shoulder and Elbow Surgeons form (ASES). If applicable, subgroup analysis will also be performed to divide patients into groups according to the energy level of ESWT, the time of intervention, and the degree of tearing of RCI. Finally, the results are submitted for publication in a peer-reviewed journal. DISCUSSION AND CONCLUSION: There is existing evidence suggesting that ESWT may contribute to the amelioration of pain and functional limitations associated with Rotator Cuff Injury (RCI). This systematic review aims to update, consolidate, and critically evaluate relevant evidence on the effects of ESWT for RCI. The anticipated outcomes may serve as a valuable reference for clinical ESWT practices, covering treatment methods, timing, and intensity. Moreover, this review aspires to provide high-quality evidence addressing the impact of ESWT on RCI-related pain. Simultaneously, the findings of this systematic review are poised to offer guidance to clinicians and rehabilitation therapists. This guidance is intended to enhance the management of pain and functional impairments experienced by individuals with RCI, ultimately leading to improvements in their physical well-being. TRIAL REGISTRATION: Protocol registration number CRD42023441407. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441407.

Effect of nano-graphene lubricating oil on particulate matter of a diesel engine.

Nano-graphene lubricating oil with appropriate concentration shows excellent performance in reducing friction and wear under different working conditions of diesel engines, and has been widely concerned. Lubricating oil has a significant impact on particulate matter (PM) emissions. At present, there are few studies on the impact of nano-graphene lubricating oil on the physicochemical properties of PM. In order to comprehensively evaluate the impact of nano-graphene lubricating oil on diesel engines, this paper mainly focused on the effects of lubricating oil nano-graphene additives on the particle size distribution and physicochemical properties of PM. The results show that, compared with pure lubricating oil, the total number of nuclear PM and accumulated PM of nano-graphene lubricating oil is significantly increased. The fractal dimension of PM of nano-graphene lubricating oil increases and its structure becomes more compact. The average fringe separation distance of basic carbon particles decreases, the average fringe length increases. The degree of ordering and graphitization of basic carbon particles are higher. The fringe tortuosity of basic carbon particles decreases, and the fluctuation of carbon layer structure of basic carbon particles decreases. Aliphatic substances in PM are basically unchanged, aromatic components and oxygen functional groups increase. The initial PM oxidation temperature and burnout temperature increase, the maximum oxidation rate temperature and combustion characteristic index decrease, and the activation energy increases, making it more difficult to oxidize. This was mainly caused by the higher graphitization degree of PM of nano-graphene lubricating oil and the increased content of aromatic substances.

Epidemiological investigation and diagnostic analysis of osteonecrosis of the femoral head in three northeastern provinces of China.

BACKGROUND: In this retrospective case investigation, we analysed the data of patients with osteonecrosis of the femoral head (ONFH) to reveal demographic and clinical diagnostic features of ONFH in three northeastern provinces of China and provide a reference for its prevention, diagnosis, and treatment. METHODS: We collected data from patients in Beijing Orthopaedic Hospital of Liaoning, focusing on the aetiology and diagnosis of ONFH. Medical records and self-designed questionnaires were used to collect information for statistical analysis, including age, aetiology, reason for glucocorticoid use, hospital level at first visit, and diagnosis. RESULTS: In total, 906 patients with complete medical records were included in the analysis. The mean patient age was 47.65 ± 12.12 years. The peak age distribution was in the 40s for men and the 50s for women. Among the total cohort, 72 patients (7.95%; 40 men and 32 women) had traumatic ONFH, 198 (21.85%; 131 men and 67 women) had steroid-induced ONFH, 230 (25.39%; 121 men and 109 women) had idiopathic ONFH, and 406 (44.81%; 397 men and 9 women) had alcohol-induced ONFH. Six hundred and twenty patients were diagnosed with ONFH at the first visit, while 286 patients were misdiagnosed, with a diagnosis rate of 68.43%. The diagnosis rate at the first visit in tertiary hospitals was 76.14%. The diagnosis rate at the first visit in second-class hospitals was 52.07%.ONFH was most likely to be misdiagnosed as lumbar disc herniation. CONCLUSIONS: Most patients with ONFH in three northeastern provinces of China were middle-aged, male, and had alcohol-induced ONFH. The misdiagnosis rate of ONFH at the first visit was very high, especially for misdiagnosis of lumbar disc herniation, indicating that the diagnosis of ONFH requires further improvement.

[Application of modified acetabular anteversion and inclination angles test system in patients undergoing total hip arthroplasty after lumbar fusion].

Objective: To investigate the accuracy and effectiveness of acetabular cup placement in total hip arthroplasty (THA) after lumbar fusion applying of modified acetabular anteversion and inclination angles test system. Methods: A clinical data of 45 patients undergoing THA for osteoarthritis between January 2018 and June 2023 was retrospectively analyzed. All patients had previously received lumbar fusion. The modified acetabular anteversion and inclination angle test system was used in 26 cases (observation group) and not used in 19 cases (control group) during THA. There was no significant difference in baseline data such as gender, age, body mass index, operative side, number of lumbar fusion segments, and preoperative Harris score between the two groups ( P>0.05). The position of acetabular prosthesis, hip function (Harris score), and incidence of complications were compared between the two groups. Results: In the observation group, all acetabular cups were in the safe zone (anteversion angle, 25°-30°) during operation, and 1 acetabular cup (3.85%) was not in the safe zone after operation. In the control group, 9 acetabular cups (47.37%) were not in the safe zone. The postoperative difference between the two groups was significant ( P<0.05). There was no significant difference between intra- and post-operative acetabular inclination angles in the observation group ( P>0.05), and the postoperative acetabular inclination angle was significantly smaller in the observation group than in the control group ( P<0.05). All incisions healed by first intention and no infection occurred. All patients were followed up 6 months. There was no significant difference in Harris score between the two groups at different time point ( P>0.05), and there were significant differences between different time points in the two groups ( P<0.05). No joint dislocation occurred in the observation group during follow-up, while dislocation occurred in 2 cases and femoral impingement syndrome occurred in 1 case of the control group. There was no significant difference in the incidence of complications between the two groups ( P>0.05). Conclusion: For THA patients with lumbar fusion, the ideal placement angle of the acetabular cup can be obtained by using the modified acetabular anteversion and inclination angles test system during operation.

Electrophysiological differences in inhibitory control processing between collegiate level soccer players and non-athletes in the absence of performance differences.

Inhibitory control, the ability to manage conflicting responses and suppress inappropriate actions, is crucial for team sports athletes, including soccer players. While previous studies have shown that soccer players possess superior inhibitory control, the underlying mechanisms responsible for this advantage remain unclear. Thus, this research aimed to investigate the neural processes involved in conflict resolution and response inhibition, comparing collegiate level soccer players with non-athletes. Participants completed a novel go/no-go task that involved conflict resolution and response inhibition, while their electroencephalograms were recorded. Despite no significant difference in behavioral performance between the two groups, soccer players exhibited notable N2 and frontal midline theta modulations in response to conflict resolution and inhibition, which were comparatively weaker in non-athletes. Our findings suggest that expertise in team sports may enhance neural sensitivity to subtle yet significant information, even without a discernible behavioral advantage.

HIF-1α facilitates glioma proliferation and invasion by activating pyroptosis signaling axis.

BACKGROUND: HIF-1α is thought to be a novel regulator which contributes to carcinogenesis. However, the mechanism underlying the effect of HIF-1α in gliomas remains largely unknown. METHODS: In the research, we demonstrate that HIF-lα mRNA and protein levels are elevated in glioma cells. The colony formation assays, transwell assays, and wound-healing assays showed that overexpression of HIF-1α promoted proliferation and invasion of glioma cells. RESULTS: Overexpression of HIF-lα also increased the expression of inflammatory factors related to pyrolysis (TNF-α, IL-10, and IL-1ß) and protein related to pyrolysis signal pathway (NLRP3, ASC, caspase-1, GSDMD, and GSDME). CONCLUSIONS: Therefore, we speculate that HIF-1α promotes the proliferation and invasion of glial cells by regulating pyrolysis pathway. These results might provide a novel strategy and target for treatment of glioma.

Abdominal multi-organ segmentation in Multi-sequence MRIs based on visual attention guided network and knowledge distillation.

PURPOSE: The segmentation of abdominal organs in magnetic resonance imaging (MRI) plays a pivotal role in various therapeutic applications. Nevertheless, the application of deep-learning methods to abdominal organ segmentation encounters numerous challenges, especially in addressing blurred boundaries and regions characterized by low-contrast. METHODS: In this study, a multi-scale visual attention-guided network (VAG-Net) was proposed for abdominal multi-organ segmentation based on unpaired multi-sequence MRI. A new visual attention-guided (VAG) mechanism was designed to enhance the extraction of contextual information, particularly at the edge of organs. Furthermore, a new loss function inspired by knowledge distillation was introduced to minimize the semantic disparity between different MRI sequences. RESULTS: The proposed method was evaluated on the CHAOS 2019 Challenge dataset and compared with six state-of-the-art methods. The results demonstrated that our model outperformed these methods, achieving DSC values of 91.83 ± 0.24% and 94.09 ± 0.66% for abdominal multi-organ segmentation in T1-DUAL and T2-SPIR modality, respectively. CONCLUSION: The experimental results show that our proposed method has superior performance in abdominal multi-organ segmentation, especially in the case of small organs such as the kidneys.

Effects of fructooligosaccharides and Saccharomyces boulardii on the compositional structure and metabolism of gut microbiota in students.

Fructooligosaccharides (FOS) are a common prebiotic widely used in functional foods. Meanwhile, Saccharomyces boulardii is a fungal probiotic frequenly used in the clinical treatment of diarrhea. Compared with single use, the combination of prebiotics and probiotics as symbiotics may be more effective in regulating gut microbiota as recently reported in the literature. The present study aimed to investigate the effects of FOS, S. boulardii and their combination on the structure and metabolism of the gut microbiota in healthy primary and secondary school students using an in vitro fermentation model. The results indicated that S. boulardii alone could not effectively regulate the community structure and metabolism of the microbiota. However, both FOS and the combination of FOS and S. boulardii could effectively regulate the microbiota, significantly inhibiting the growth of Escherichia-Shigella and Bacteroides, and controlling the production of the gases including H2S and NH3. In addition, both FOS and the combination could significantly promote the growth of Bifidobacteria and Lactobacillus, lower environmental pH, and enhance several physiological functions related to synthesis and metabolism. Nevertheless, the combination had more unique benefits as it promoted the growth of Lactobacillus, significantly increased CO2 production and enhanced the functional pathways of carbon metabolism and pyruvic acid metabolism. These findings provide guidance for clinical application and a theoretical basis for the development of synbiotic preparations.

Effect of extracorporeal shockwave therapy for rotator cuff tendinopathy: a systematic review and meta-analysis.

BACKGROUND: Rotator cuff tendinopathy (RCT) is a widespread musculoskeletal disorder and a primary cause of shoulder pain and limited function. The resulting pain and limited functionality have a detrimental impact on the overall quality of life. The purpose of this study was to perform a systematic review of the effects of extracorporeal shock wave therapy (ESWT) for RCT. METHODS: The literature search was conducted on the following databases from inception to February 20, 2024: PubMed, Web of Science, the Cochrane Library, Scopus, MEDLINE, EMBASE, EBSCO, and China National Knowledge Infrastructure (CNKI) were checked to identify the potential studies exploring the effect of ESWT for the treatment of Rotator cuff tendinopathy (Calcification or non-calcification), control group for sham, other treatments (including placebo), without restriction of date, language. Two researchers independently screened literature, extracted data, evaluated the risk of bias in the included studies, and performed meta-analysis using RevMan 5.3 software. RESULTS: A total of 16 RCTs with 1093 patients were included. The results showed that compared with the control group, ESWT for pain score Visual Analogue Scale/Score (VAS) (SMD = -1.95, 95% CI -2.47, -1.41, P < 0.00001), function score Constant-Murley score (CMS) (SMD = 1.30, 95% CI 0.67, 1.92, P < 0.00001), University of California Los Angeles score (UCLA) (SMD = 2.69, 95% CI 1.64, 3.74, P < 0.00001), American Shoulder and Elbow Surgeons form (ASES) (SMD = 1.29, 95% CI 0.93, 1.65, P < 0.00001), Range of motion (ROM) External rotation (SMD = 1.00, 95% CI 0.29, 1.72, P = 0.02), Total effective rate (TER) (OR = 3.64, 95% CI 1.85, 7.14, P = 0.0002), the differences in the above results were statistically significant. But ROM-Abduction (SMD = 0.72, 95% CI -0.22, 1.66, P = 0.13), the difference was not statistically significant. CONCLUSION: Currently limited evidence suggests that, compared with the control group, ESWT can provide better pain relief, functional recovery, and maintenance of function in patients with RCT.

CARMA3 Drives NF-κB Activation and Promotes Intervertebral Disc Degeneration: Involvement of CARMA3-BCL10-MALT1 Signalosome.

Intervertebral disc degeneration (IDD) diseases are common and frequent diseases in orthopedics. The caspase recruitment domain (CARD) and membrane-associated guanylate kinase-like protein 3 (CARMA3) is crucial in the activation of the NF-κB pathway. However, the biological function of CARMA3 in IDD remains unknown. Here, CARMA3 expression was elevated in nucleus pulposus (NP) tissues of IDD rats and nutrient deprivation (ND)-induced NP cells. The main pathological manifestations observed in IDD rats were shrinkage of the NP, reduction of NP cells, fibrosis of NP tissues, and massive reduction of proteoglycans. These changes were accompanied by a decrease in the expression of collagen II and aggrecan, an increase in the expression of the extracellular matrix (ECM) catabolic proteases MMP-3, MMP-13, and metalloprotease with ADAMTS-5, and an increase in the activity of the pro-apoptotic protease caspase-3. The expression of p-IκBαSer32/36 and p-p65Ser536 was also upregulated. However, these effects were reversed with the knockdown of CARMA3. Mechanistically, CARMA3 bound to BCL10 and MALT1 to form a signalosome. Knockdown of CARMA3 reduced the CARMA3-BCL10-MALT1 signalosome-mediated NF-κB activation. CARMA3 activated the NF-κB signaling pathway in a manner that bound to BCL10 and MALT1 to form a signalosome, which affects NP cell damage and is involved in the development of IDD. This supports CARMA3-BCL10-MALT1-NF-κB as a promising targeting axis for the treatment of IDD.

A universal strategy to enhance photothermal conversion efficiency by regulating the molecular aggregation states for safe photothermal therapy of bacterial infections.

Photothermal therapy (PTT) has emerged as a promising approach for treating bacterial infections. However, achieving a high photothermal conversion efficiency (PCE) of photothermal agents (PTAs) remains a challenge. Such a problem is usually compensated by the use of a high-intensity laser, which inevitably causes tissue damage. Here, we present a universal strategy to enhance PCE by regulating the molecular aggregation states of PTAs within thermoresponsive nanogels. We demonstrate the effectiveness of this approach using aggregation-induced emission (AIE) and aggregation-caused quenching (ACQ) PTAs, showing significant enhancements in PCE without the need for intricate molecular modifications. Notably, the highest PCEs reach up to 80.9% and 64.4% for AIE-NG and ACQ-NG, respectively, which are nearly 2-fold of their self-aggregate counterparts. Moreover, we elucidate the mechanism underlying PCE enhancement, highlighting the role of strong intermolecular π-π interactions facilitated by nanogel-induced volume contraction. Furthermore, we validate the safety and efficacy of this strategy in in vitro and in vivo models of bacterial infections at safe laser power densities, demonstrating its potential for clinical translation. Our findings offer a straightforward, universal, and versatile method to improve PTT outcomes while minimizing cytotoxicity, paving the way for enhanced treatment of bacterial infections with safe PTT protocols.

Receptor-activated transcription factors and beyond: multiple modes of Smad2/3-dependent transmission of TGF-ß signaling.

Transforming growth factor ß (TGF-ß) is a pleiotropic cytokine that is widely distributed throughout the body. Its receptor proteins, TGF-ß type I and type II receptors, are also ubiquitously expressed. Therefore, the regulation of various signaling outputs in a context-dependent manner is a critical issue in this field. Smad proteins were originally identified as signal-activated transcription factors similar to signal transducer and activator of transcription proteins. Smads are activated by serine phosphorylation mediated by intrinsic receptor dual specificity kinases of the TGF-ß family, indicating that Smads are receptor-restricted effector molecules downstream of ligands of the TGF-ß family. Smad proteins have other functions in addition to transcriptional regulation, including post-transcriptional regulation of micro-RNA processing, pre-mRNA splicing, and m6A methylation. Recent technical advances have identified a novel landscape of Smad-dependent signal transduction, including regulation of mitochondrial function without involving regulation of gene expression. Therefore, Smad proteins are receptor-activated transcription factors and also act as intracellular signaling modulators with multiple modes of function. In this review, we discuss the role of Smad proteins as receptor-activated transcription factors and beyond. We also describe the functional differences between Smad2 and Smad3, two receptor-activated Smad proteins downstream of TGF-ß, activin, myostatin, growth and differentiation factor (GDF) 11, and Nodal.

Investigation on vehicle occupant dummy applicability for under-foot impact loading conditions.

PURPOSE: Under-foot impact loadings can cause serious lower limb injuries in many activities, such as automobile collisions and underbody explosions to military vehicles. The present study aims to compare the biomechanical responses of the mainstream vehicle occupant dummies with the human body lower limb model and analyze their robustness and applicability for assessing lower limb injury risk in under-foot impact loading environments. METHODS: The Hybrid III model, the test device for human occupant restraint (THOR) model, and a hybrid human body model with the human active lower limb model were adopted for under-foot impact analysis regarding different impact velocities and initial lower limb postures. RESULTS: The results show that the 2 dummy models have larger peak tibial axial force and higher sensitivity to the impact velocities and initial postures than the human lower limb model. In particular, the Hybrid III dummy model presented extremely larger peak tibial axial forces than the human lower limb model. In the case of minimal difference in tibial axial force, Hybrid III's tibial axial force (7.5 kN) is still 312.5% that of human active lower limb's (2.4 kN). Even with closer peak tibial axial force values, the biomechanical response curve shapes of the THOR model show significant differences from the human lower limb model. CONCLUSION: Based on the present results, the Hybrid III dummy cannot be used to evaluate the lower limb injury risk in under-foot loading environments. In contrast, potential improvement in ankle biofidelity and related soft tissues of the THOR dummy can be implemented in the future for better applicability.

Exploring the influence of a 4-week aerobic exercise intervention on cognitive control processes in young adults: An SFT and DDM study.

Prior research has highlighted the potential impact of aerobic exercise on cognitive functioning, particularly in situations demanding heightened cognitive control. However, the mechanism underlying this cognitive enhancement has remained unknown. To address this issue, this study examined the impact of a 4-week aerobic exercise program on cognitive control processes in young male adults (aerobic exercise group: n=36, aged 21.42±1.13years) in comparison to a control group that received no treatment (n=33, aged 21.82±1.76years). We employed the redundant-target Stroop task to investigate inhibition processes at both perceptual and semantic stages. Utilizing systems factorial technology and the drift diffusion model, we assessed changes in resilience capacity and the underlying cognitive mechanisms. Our primary findings revealed a significant reduction in mean response times (RTs) in the aerobic exercise group, accompanied by a decrease in RT variability when inhibiting semantic processing. Resilience capacity significantly declined in both groups at similar levels. Notably, the aerobic exercise group exhibited an enhanced drift rate during automatic response inhibition and reduced non-decision time in the condition involving the inhibition of perceptual information. This study deepens our understanding of how a 4-week aerobic exercise program enhances cognitive control, affecting distinct cognitive processes, including processing speed, information accumulation during automatic response inhibition, and sensory and motor processes in perceptual conflicts. Our research underscores the potential of aerobic exercise as a means to boost cognitive control among young adults.

Optimizing Mn in Prussian blue analogs with double redox active sites to induce boosted Zn2+ storage.

Prussian Blue analogs (PBAs) are a suitable aqueous zinc-ion batteries (AZIBs) cathode material, but they face issues related to low specific capacity and cycling lifespan due to insufficient active sites and poor ion de-intercalation structural stability. In this study, Mn-Prussian Blue Analog (Mn-PBA) is fabricated using a simple co-precipitation method and the morphology of Mn-PBA is further optimized through artificially manipulating concentration gradients strategy, effectively enhancing the structural stability of Zn2+ de-intercalation. Furthermore, the introduction of Mn established dual Zn2+ active centers in Mn-PBA (Mn-O and Fe(CN)6]4-/[Fe(CN)6]3-), leading to an increased specific capacity. As a proof of concept for AZIBs, the optimized Mn-PBA-3 cathode exhibits a high reversible specific capacity of 143.5 mAh/g and maintains a capacity retention of 88.5 % after 250 cycles at 1 A/g, surpassing commercial MnO2 (30.5 mAh/g after 100 cycles). Mn-PBA-3 also delivers a high capacity of 79.0 mA h g-1 after 2000 cycles of 10 A/g. The mechanism of the Zn2+ double redox reaction of Mn-PBA-3 has been revealed in detail by in situ Raman and a series of ex situ techniques. Under a high operating voltage window of 0-1.9 V, Zn//Mn-PBA-3 demonstrates a capacity of 99.3 mAh/g after 800 cycles (5 A/g) by assembling zinc ion button battery. This work has reference significance for structurally modulated PBAs used in high performance AZIBs.

Protective Mechanism of Rosa roxburghii Tratt Fermentation Broth against Ultraviolet-A-Induced Photoaging of Human Embryonic Skin Fibroblasts.

This study takes the fruit of Rosa roxburghii Tratt (RRT) as a fermentation substrate and carries out a quantitative visual analysis of the domestic and foreign literature on screenings of five different lactic acid bacteria to obtain a fermentation broth. Systemic anti-photoaging effects are analyzed at the biochemical, cellular, and molecular biological levels. DPPH and ABTS free radical scavenging activities are used to verify the antioxidant capacity of the RRT fruit fermentation broth in vitro. Human embryonic skin fibroblasts (HESs) are used to establish a UVA damage model, and the antioxidant capacity of the RRT fruit fermentation broth is verified in terms of intracellular reactive oxygen species (ROS) and antioxidant enzyme activity. RT-qPCR and ELISA are used to detect the expression of TGF-ß/Smad, MMPs, and the MAPK/AP-1 and Nrf2/Keap-1 signaling pathways in order to explore the anti-oxidation and anti-photoaging effects of the RRT fruit fermentation broth by regulating different signaling pathways. The results show that an RRT fruit fermentation broth can effectively protect cells from oxidative stress caused by UVA and has significant anti-photoaging effects, with the co-cultured Lactobacillus Yogurt Starter LYS-20297 having the highest overall effect.

Pt-Modified High Entropy Rare Earth Oxide for Efficient Hydrogen Evolution in pH-Universal Environments.

The development of efficient and stable catalysts for hydrogen production from electrolytic water in a wide pH range is of great significance in alleviating the energy crisis. Herein, Pt nanoparticles (NPs) anchored on the vacancy of high entropy rare earth oxides (HEREOs) were prepared for the first time for highly efficient hydrogen production by water electrolysis. The prepared Pt-(LaCeSmYErGdYb)O showed excellent electrochemical performances, which require only 12, 57, and 77 mV to achieve a current density of 100 mA cm-2 in 0.5 M H2SO4, 1.0 M KOH, and 1.0 M PBS environments, respectively. In addition, Pt-(LaCeSmYErGdYb)O has successfully worked at 400 mA cm-2 @ 60 °C for 100 h in 0.5 M H2SO4, presenting the high mass activity of 37.7 A mg-1Pt and turnover frequency (TOF) value of 38.2 s-1 @ 12 mV, which is far superior to the recently reported hydrogen evolution reaction (HER) catalysts. Density functional theory (DFT) calculations have revealed that the interactions between Pt and HEREO have optimized the electronic structures for electron transfer and the binding strength of intermediates. This further leads to optimized proton binding and water dissociation, supporting the highly efficient and robust HER performances in different environments. This work provides a new idea for the design of efficient RE-based electrocatalysts.

Autoimmune nodopathy with anti-contactin 1 antibody characterized by cerebellar dysarthria: a case report and literature review.

Background: Autoimmune nodopathy (AN) has emerged as a novel diagnostic category that is pathologically different from classic chronic inflammatory demyelinating polyneuropathy. Clinical manifestations of AN include sensory or motor neuropathies, sensory ataxia, tremor, and cranial nerve involvement. AN with a serum-positive contactin-1 (CNTN1) antibody usually results in peripheral nerve demyelination. In this study, we reported a rare case of AN with CNTN1 antibodies characterized by the presence of CNTN1 antibodies in both serum and cerebrospinal fluid, which is associated with cerebellar dysarthria. Methods: A 25-year-old man was admitted to our hospital due to progressive dysarthria with limb tremors. The patient was initially diagnosed with peripheral neuropathy at a local hospital. Three years after onset, he was admitted to our hospital due to dysarthria, apparent limb tremor, and limb weakness. At that time, he was diagnosed with spinocerebellar ataxia. Eight years post-onset, during his second admission, his condition had notably deteriorated. His dysarthria had evolved to typical distinctive cerebellar characteristics, such as tremor, loud voice, stress, and interrupted articulation. Additionally, he experienced further progression in limb weakness and developed muscle atrophy in the distal limbs. Magnetic resonance imaging (MRI), nerve conduction studies (NCS), and autoimmune antibody tests were performed. Results: The results of the NCS suggested severe demyelination and even axonal damage to the peripheral nerves. MRI scans revealed diffuse thickening of bilateral cervical nerve roots, lumbosacral nerve roots, cauda equina nerve, and multiple intercostal nerve root sheath cysts. Furthermore, anti-CNTN1 antibody titers were 1:10 in the cerebrospinal fluid (CSF) and 1:100 in the serum. After one round of rituximab treatment, the patient showed significant improvement in limb weakness and dysarthria, and the CSF antibodies turned negative. Conclusion: Apart from peripheral neuropathies, cerebellar dysarthria (central nervous system involvement) should not be ignored in AN patients with CNTN1 antibodies.

Synergistic effects of ceftazidime/avibactam combined with meropenem in a murine model of infection with KPC-producing Klebsiella pneumoniae.

OBJECTIVES: The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of 'first-line' antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is combination therapies that result in synergistic activity against K. pneumoniae carbapenemase: producing K. pneumoniae (KPC-Kp) isolates and preventing the emergence of KPC mutants resistant to ceftazidime/avibactam are needed in lieu of novel antibiotics. METHODS: To evaluate their synergistic activity, antibiotic combinations were tested against 26 KPC-Kp strains. Antibiotic resistance profiles, molecular characteristics and virulence genes were investigated by susceptibility testing and whole-genome sequencing. Antibiotic synergy was evaluated by in vitro chequerboard experiments, time-killing curves and dose-response assays. The mouse thigh model was used to confirm antibiotic combination activities in vivo. Additionally, antibiotic combinations were evaluated for their ability to prevent the emergence of ceftazidime/avibactam resistant mutations of blaKPC. RESULTS: The combination of ceftazidime/avibactam plus meropenem showed remarkable synergistic activity against 26 strains and restored susceptibility to both the partnering antibiotics. The significant therapeutic effect of ceftazidime/avibactam combined with meropenem was also confirmed in the mouse model and bacterial loads in the thigh muscle of the combination groups were significantly reduced. Furthermore, ceftazidime/avibactam plus meropenem showed significant activity in preventing the occurrence of resistance mutations. CONCLUSIONS: Our results indicated that the combination of ceftazidime/avibactam plus meropenem offers viable therapeutic alternatives in treating serious infections due to KPC-Kp.