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Deep learning has driven major breakthroughs in protein structure prediction; however, one of the next critical steps forward is accurately predicting how proteins interact with small-molecule ligands, to enable real-world applications such as drug discovery. Recent cofolding methods aim to address this challenge, but evaluating their performance has been inconclusive because of the lack of relevant benchmarking datasets. Here we present a comprehensive evaluation of four leading all-atom cofolding methods using our newly introduced benchmark dataset, Runs N' Poses. Runs N' Poses comprises 2,600 high-resolution protein-ligand systems released after the training cutoff used by these methods. We demonstrate that current cofolding approaches largely memorize ligand poses from their training data, hindering their use for de novo drug design. With this assessment and benchmark dataset, we aim to accelerate progress in the field by allowing for a more realistic assessment of the current state-of-the-art deep learning methods for predicting protein-ligand interactions.

Radiation cystitis is a common complication of pelvic radiotherapy that significantly compromises clinical outcomes. A principal pathogenic factor is the accumulation of cell-free DNA (cfDNA) released from damaged cells, which promotes inflammatory cytokine production and disturbs tissue homeostasis. The study aims to engineer a self-propelled nanozyme motor that clears cfDNA and restores redox balance as a dual-mechanistic therapy for radiation cystitis. The system operated using endogenous urea, a naturally abundant metabolite present in bladder urine, enabling sustained and coordinated autonomous propulsion following intravesical instillation. This mobility facilitated extensive mucosal coverage and deeper penetration, allowing the motors to capture cfDNA deposited on the irradiated mucosal surface. The nanozyme core eliminated radiation-induced reactive oxygen species, resulting in a reduction of oxidative stress. These combined effects suppressed activation of the cGAS-STING signaling pathway and lowered the release of pro-inflammatory cytokines. Both in vitro and in vivo investigations verified the anti-inflammatory activity of this platform, indicating its translational relevance for radiation cystitis treatment.

In August 2025, an updated International Multidisciplinary Classification of Interstitial Pneumonias was released by the European Respiratory Society (ERS) and American Thoracic Society (ATS). For the first time, the "idiopathic-only" paradigm has been transcended through the integration of secondary interstitial lung diseases (ILD) into a unified framework. Grounded in recent advances in ILD research, major changes have been introduced to disease patterns, diagnostic terminology, subcategories, and diagnostic approach. Actual histopathologic findings are more accurately represented by the new schema, and clearer, more actionable guidance for patient management is provided to clinicians. The pathological dimensions of the update are highlighted herein, with key innovations outlined, newly introduced subcategories, terminologies, and categorization systems elucidated, and a systematic overview of the histological characteristics of major patterns offered. Additionally, the opportunities and challenges that the new classification presents to pathologists are discussed. 2025年8月，欧洲呼吸学会（European Respiratory Society，ERS）/美国胸科学会（American Thoracic Society，ATS）发布新版《间质性肺炎国际多学科分类》更新，首次突破“特发性”框架，将继发性间质性肺病纳入统一体系，并依据近年来间质性肺病的相关研究进展对疾病模式、诊断术语、亚类分组、诊断方法等作出重大调整。新分类更加贴近疾病实际病理学表现，也为临床治疗管理提供了更强的指导价值。本文将聚焦其中的病理相关内容，梳理核心变革，解读新增亚类、术语与分组设置，系统描述主要模式的组织学特征，并探讨更新给病理医师带来的机遇与挑战。.

The neuromodulator histamine regulates key processes in many circuits of the adult and developing brain, including striatum. However, striatal innervation by histaminergic afferents is very sparse making the physiological sources of histamine unclear. Here sources of striatal histamine were investigated during early postnatal development and specifically during the second postnatal week in mice of either sex. Firstly, a combination of patch-clamp recording and optogenetic stimulation in brain slices demonstrates that during this period exogenously applied histamine modulates both the intrinsic properties of developing D1 and D2 striatal spiny projection neurons (SPNs) and synaptic transmission at afferents coming from the mPFC and visual cortex. Secondly, immunohistochemistry for histamine reveals a brain region adjacent to the caudal striatum densely innervated by histaminergic axons and corresponding to the oval nucleus of bed nucleus of stria terminalis (ovBNST). Thirdly, electrical stimulation of the ovBNST leads to significant and detectable levels of histamine in striatum, as assessed by fast scan cyclic voltammetry and fluorescent histamine sensors in brain slices as well as in vivo. Lastly, electrical stimulation of the ovBNST nucleus, at frequencies mimicking normal active histamine neurons, can release sufficient levels of histamine to modulate excitatory synaptic transmission from mPFC onto striatal SPNs through histamine H3 receptors. Together, these results provide evidence for the existence of the ovBNST as an extrastriatal source of histamine during early brain development and postulates a new view of the modus operandi of histamine in that it can cross anatomical and functional boundaries and act as a paracrine neuromodulator.Significance statement The neuromodulator histamine is synthesized by neurons located in the tuberomammillary nucleus (TMN) of the hypothalamus and is released from their axons in many brain regions. There the histaminergic system regulates many key processes, and has been shown to be dysregulated in a variety of neurological and neurodevelopmental disorders. Key to understanding the physiological roles of histamine and to generate possible interventions when dysregulated is to know both the local sources of histamine and its mode of action. Using the striatum as an exemplar we provide here the first evidence that sources of histamine may lie outside of anatomical boundaries and that histamine can act as a paracrine neuromodulator during early brain development contrasting with many other neuromodulators.

Closed reduction of distal radius fractures is painful, and current analgesic strategies may be inadequate. Ultrasound-guided lateral infraclavicular brachial plexus block may offer complete analgesia and muscle relaxation, potentially improving patient comfort and reduction quality. However, benefits and challenges regarding anesthetic agents for this procedure remain unclear. In this randomized, controlled, blinded, noninferiority trial, 63 adults with distal radius fractures requiring closed reduction received a lateral infraclavicular block with either 30 mL of ropivacaine 0.5%, lidocaine 1% with epinephrine, or ropivacaine 0.2%. The primary outcome was block success at 45 min, defined as complete sensory and extensive motor block of the radial, musculocutaneous, ulnar, and median nerves. Noninferiority was assessed using a margin of 20%. Exploratory outcomes included sensory and motor block assessments, time to pain relief, block duration, pain during reduction, patient satisfaction, quality of closed reduction, fracture treatments, and safety. Ropivacaine 0.2% was statistically inferior to ropivacaine 0.5% in achieving block success at 45 min (risk ratio (RR) 0.63, 97.5% CI 0.40-0.99). Lidocaine 1% with epinephrine did not meet the predefined noninferiority criteria for block success (RR 0.95, 97.5% CI 0.73-1.22) but did provide comparable analgesia with a shorter block duration. Pain scores during reduction were low across all groups, with a significant decrease in pain from baseline. Patient satisfaction was high in all groups. No significant differences were found in the quality of closed reduction, safety, or fracture treatments. Lateral infraclavicular block with ropivacaine 0.2% failed to demonstrate noninferiority for block success and was statistically inferior to ropivacaine 0.5%. Inferiority testing should be interpreted cautiously within the context of a noninferiority design, although the results suggest reduced effectiveness for distal radius fracture reduction. Lidocaine 1% with epinephrine yielded inconclusive results for noninferiority on block success, but provided a shorter block duration without compromising analgesia, patient satisfaction, or quality of reduction. ClinicalTrials.gov Identifier NCT06379490 (released April 23, 2024); https://clinicaltrials.gov/study/NCT06379490; EUCT Identifier 2024-510,572-20-00; https://euclinicaltrials.eu/ctis-public/view/2024-510572-20-00.

We present CaryaData, an image dataset of Chinese hickory (Carya cathayensis Sarg.) fruit maturity acquired in natural orchards in Zhejiang Province, China. The dataset comprises 1,661 canopy images (3024 × 3024 pixels) spanning key developmental stages from fruit enlargement to harvest. Within these images, 3,211 visually discernible fruit instances are annotated with axis-aligned bounding boxes and assigned to three maturity levels (maturity1-maturity3) or an unknown class for visually uncertain cases (labelled as unknown in the released annotations), based on pericarp colour, surface blemishes and cracking status. Data construction followed a rigorous quality-control workflow, including automated image quality filtering, standardised maturity interpretation, and a two-round annotation process with double-blind cross-validation of all images. To facilitate modelling and quantitative analysis, CaryaData also provides a derived subset uniformly resized to 640 × 640 pixels, together with image-level and instance-level metadata describing illumination, maturity composition and geometric properties of targets. Physical detachment force experiments confirmed the biological consistency of the maturity grading, and benchmark experiments showed that CaryaData supports deep learning-based fruit maturity assessment, offering a reusable resource for research on maturity evaluation, yield estimation and intelligent harvesting in Chinese hickory orchards.

Astrocytes play a key role in regulating glioma cell volume, a major determinant of tumor invasiveness. We previously reported that astrocyte-derived extracellular vesicles (ADEVs) transfer microRNA miR-124 to murine glioma cells, impairing cell volume regulation and reducing the functional expression of volume-regulated anion channel (VRAC). Here, we identify the intermediate-conductance Ca2+-activated K+ (IK) channel, the only volume-regulated K+ channel acting in concert with VRAC in GL261 glioma cells, as an additional indirect target of miR-124. Mechanistically, ADEV-derived miR-124 decreases the expression of ryanodine receptor type-1 (RyR1) and inositol 1,4,5-trisphosphate receptor type-3 (IP3R3), the principal endoplasmic reticulum (ER) Ca2+ release channels in these cells. This reduction in ER-mediated Ca2+ signaling markedly decreases ERK1/2 phosphorylation and IK channel gene transcription. Consistent with these molecular effects, fetal bovine serum-induced IK channel activation, driven by ER Ca2+ release, was strongly reduced by ADEVs and miR-124, and three-dimensional migration was impaired. Notably, combined pharmacological inhibition of IK and VRAC recapitulated the deficits in volume regulation induced by ADEVs and miR-124. Collectively, these findings show that ADEVs restrict glioma cell migration through a miR-124-dependent pathway that suppresses ER Ca2+ release, reduces ERK1/2 activation, and diminishes IK channel expression and function. Together with our previous in vivo evidence for ADEVs- and miR-124 -mediated targeting of VRAC, these results identify coordinated regulation of K+ and Cl⁻ channels as a mechanism by which astrocytes constrain glioma progression.

Mechanical recanalization of distal and small medium vessel occlusions (DVOs and MeVOs) is technically challenging and likely associated with higher complication rates. Previous studies have shown promising results using Q aspiration catheters in MeVOs. We report our experience with Q catheters in an even more distal cohort of DVOs and small MeVOs, focusing on safety and efficacy. We retrospectively reviewed our institutional stroke database for patients with DVOs or MeVOs treated using Q catheters. Baseline characteristics, technical outcomes including modified Thrombolysis in Cerebral Infarction (mTICI) score and modified first pass effect (mFPE), as well as clinical outcomes measured by the 90-day modified Rankin Scale (mRS) were analyzed. Outcomes were stratified by occlusion type and treatment technique. Periprocedural complications and their clinical impact were systematically assessed. 57 occlusions in 47 patients were included. Mean age was 75.5 ± 12.7 years. Median National Institutes of Health Stroke Scale score was 7.7 ± 4.6 at admission and 4.9 ± 5.5 at discharge, while the rate of 90-day- mRS ≤ 2 was 37%. 39 were DVOs and 18 small MeVOs. Successful recanalization (mTICI ≥2b) was achieved in 75% overall, with lower rates in DVOs (71%) than MeVOs (83%). Stent retriever-assisted aspiration resulted in higher recanalization rates than aspiration alone (82% vs. 37%). mFPE was achieved in 42%. Periprocedural complications occurred in 9% of cases with no symptomatic intracranial hemorrhage (sICH) or PH2. Q catheters appear to be safe and effective for DVOs and small MeVOs, achieving favorable recanalization rates with an acceptable complication profile. While the study is limited by its small sample size and retrospective design, these findings support the potential of Q catheters as a valuable tool in the treatment of distal and small vessel occlusions. Nevertheless, consistent to the recently published large distal trials, recanalization rates are lower, and complications occur more often in DVOs than in MeVOs, reflecting a different balance between the technical challenges and the smaller expected clinical benefit.

To evaluate the safety and feasibility of the enhanced MicroHand S surgical robot system in urological minimally invasive cancer surgeries, in alignment with the IDEAL-D Framework Stage 2a. Procedures were performed by an experienced urologist from the Affiliated Hospital of Qingdao University using the MicroHand S surgical robot system. Patients requiring radical cystectomy, partial nephrectomy, or radical prostatectomy were enrolled. The primary endpoint was the rate of unplanned conversion from robot-assisted surgery to conventional laparoscopic or open surgery. An independent Clinical Expert Committee reviewed the study to adjudicate the occurrence of adverse events (AEs) and serious adverse events (SAEs). All patients were followed for 1 year postoperatively. These procedures included 12 radical cystectomies, 8 radical prostatectomies, and 3 partial nephrectomies. All procedures were completed successfully without the need for conversion to conventional laparoscopic or open surgery. No robotic devices or surgical instruments related AEs were recorded during the procedure. All patients had a postoperative Clavien-Dindo classification of grade Ⅰ before discharge (100%). No patients returned to the operating room within 24 hours of surgery. At 1- year follow-up none patient presented a tumor recurrence. The MicroHand S system is safe and feasible for complex urological MICS, supporting further clinical trial recruitment. The study was registered at Clinicaltrials.gov (https://trialsearch.who.int/Trial2.aspx?TrialID=NCT05462392), registration number: NCT05462392.

Alzheimer's disease (AD) is a neurodegenerative condition marked by amyloid β (Aβ) plaque accumulation, contributing to cognitive decline. Epigallocatechin (EGC) has shown potential in preventing Aβ aggregation and disrupting fibrils, but its low bioavailability and poor blood-brain barrier (BBB) penetration limit its therapeutic use. To address these challenges, this study introduces the first functionalized nanosystem developed for the EGC delivery. Liposomal EGC was optimized and conjugated with transferrin (Tf), given literature evidence supporting its potential role in BBB-targeting strategies. The optimal formulation exhibited a mean diameter of 127 ± 14 nm, a polydispersity index of 0.20 ± 0.02, a zeta potential of -0.9 ± 0.3 mV, and an encapsulation efficiency of 20 ± 3%, properties that were maintained after 1 month of storage at 4 °C. Moreover, the nanosystem exhibited a controlled and sustained release, achieving 77 ± 11% release over 9 days. In terms of therapeutic activity, the nanoformulation showed an antioxidant capacity of 53 ± 6%, demonstrating its potential to neutralize free radicals, a key factor in AD progression. Furthermore, targeted liposomal EGC completely inhibited Aβ fibrillation, as demonstrated by thioflavin T assays. Data revealed a reduction in parallel β-sheet content from 44 ± 4% to 33 ± 5% and an increase in α-helices from 31 ± 5 to 45 ± 4%, suggesting inhibition of fibril formation. Additionally, Tf conjugation enhanced liposome uptake by endothelial cells without inducing cytotoxicity. These findings support the potential of this nanosystem as a promising platform for further investigation in AD.

Efficient delivery of therapeutic agents to target lesions persists as a significant challenge in cancer therapy. Herein, we report a biomimetic, near-infrared (NIR)/ultrasound (US)-responsive bifunctional drug delivery system that provides spatiotemporally programmed chemo-photodynamic therapy (PDT)/sonodynamic therapy (SDT) for prostate cancer. The designed formulation comprises reduction-sensitive nanogels encapsulated within RBC membranes, surface-functionalized with LHRH for targeted delivery (termed LHRH-RBC/Ce6-NG/HCPT). Chlorin e6 (Ce6), a photosensitizer and sonosensitizer, was embedded within the RBC membrane shell, while the anticancer compound 10-hydroxycamptothecin (HCPT) was encapsulated within the nanogel core structure of poly(L-glutamic acid)-poly(L-phenylalanine-co-L-cystine) nanogels. Compared with free Ce6 and HCPT, the designed formulation markedly extended systemic retention and improved intratumoral deposition. Furthermore, tumor‑localized NIR or US stimulation induced the production of reactive oxygen species (ROS), which enhanced nanovesicle uptake by increasing tumor cell membrane fluidity and concurrently disrupted the RBC membrane, leading to the rapid, intracellular glutathione-triggered release of HCPT. The released HCPT further synergized with PDT/SDT to amplify ROS generation and exacerbate mitochondrial dysfunction, thereby enhancing tumor cell killing. The spatiotemporally coupled dynamic-chemotherapy maximized on-tumor efficacy while minimizing off-target toxicity. In vivo studies confirmed that, LHRH-RBC/Ce6-NG/HCPT achieved potent synergistic effects in both PDT/chemotherapy and SDT/chemotherapy, demonstrating its potential as an effective and safe treatment strategy for prostate cancer.

Cognitive deficits associated with chronic pain pose a significant burden on a patient's quality of life. Emerging evidence indicates that Toll-like receptor 4 (TLR4), a pattern recognition receptor implicated in neuroinflammatory signaling that can disrupt synaptic plasticity and memory processes. However, the specific involvement of TLR4 in the development of neuropathic pain-related cognitive deficits has not been fully elucidated. In this investigation, we observed an upregulation of TLR4 expression within hippocampal neurons in male mice subjected to chronic constriction injury (CCI) relative to sham group. Notably, in separate experimental cohorts, TLR4-knockout and neuron-specific TLR4-knockdown mice exhibited improved cognitive function compared to wild-type controls, alongside attenuated neuroinflammatory responses, reduced neuronal apoptosis, and enhanced preservation of hippocampal neuroplasticity. Concurrently, elevated concentrations of high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecule, were detected in the sciatic nerve, serum, and hippocampal tissues following CCI. Furthermore, increased co-localization of HMGB1 with TLR4 was evident in the hippocampus. Exogenous administration of HMGB1 augmented HMGB1 and TLR4 levels in the hippocampus and worsened memory functions that depend on hippocampal integrity. Conversely, inhibition of HMGB1 with glycyrrhizin, which subsequently attenuates TLR4 activation, ameliorated cognitive impairments induced by CCI. Collectively, these results support a model in which HMGB1, elevated during chronic neuropathic pain, contributes to cognitive deficits via a TLR4-dependent mechanism, triggering downstream inflammatory and apoptotic cascades and impairing synaptic plasticity.Significance Statement Chronic neuropathic pain is frequently accompanied by debilitating cognitive deficits, yet the underlying mechanisms linking peripheral nerve injury to central nervous system dysfunction remain poorly understood, hindering the development of targeted therapies. This study identifies the HMGB1/ TLR4 signaling axis as a critical mediator driving these cognitive impairments. We demonstrate that HMGB1, released after nerve injury, activates hippocampal TLR4, triggering neuroinflammation, neuronal apoptosis, and synaptic deficits. Importantly, genetic deletion or neuronal-specific knockdown of TLR4, as well as pharmacological inhibition of the HMGB1/TLR4 interaction, rescues cognitive function. These findings elucidate a precise molecular pathway connecting peripheral neuropathic pain to cognitive decline and establish the HMGB1/TLR4 axis as a promising therapeutic target for preventing or treating pain-associated cognitive dysfunction.

Aerosolized or vaporized glycols have been proposed as a safe and low-cost measure for air sanitization, but limited information is available on their efficacy in real-world conditions. We evaluated 2 commercial glycol products, including a dipropylene glycol aerosol spray air sanitizer containing 30% to 60% ethanol and a triethylene glycol product released as a vapor over up to 48 hours. In a simulated patient room with 8 air changes per hour, we tested the efficacy of both products in reducing aerosolized bacteriophages Phi6 and MS2 in air and settling on disks, and the triethylene glycol vapor in reducing the viruses and bacterial pathogens and Candidozyma auris on steel disks. Both products significantly reduced recovery of the bacteriophages in air and significantly reduced recovery of bacteriophage Phi6, but not bacteriophage MS2, on settle disks. After 16 or 48 hours, the triethylene glycol vapor reduced recovery of Phi6, Acinetobacter baumanii, and C. auris by >1 log10, and reduced methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and Klebsiella pneumoniae by ~0.5 log10. The glycol products could be an effective adjunctive method to reduce airborne viruses, and with prolonged exposure might have a modest impact on surface contamination with bacteria and fungi.

Reactive nodular fibrous pseudotumor is a rare benign fibroinflammatory lesion of the gastrointestinal tract and mesentery that can closely mimic malignant disease on clinical examination and imaging. Most reported cases are associated with prior abdominal surgery, trauma, or inflammation. Omental involvement is particularly uncommon, and preoperative diagnosis remains difficult because of its rarity and the limited description of multimodality imaging findings. We report a rare case of omental reactive nodular fibrous pseudotumor in a young man without any history of abdominal surgery, trauma, or abdominal discomfort, highlighting its unusual presentation and diagnostic features. A 31-year-old man presented with a palpable abdominal mass that had been present for more than 1 month. He had no previous abdominal surgery, trauma, or gastrointestinal symptoms. Contrast-enhanced computed tomography revealed multiple well-defined solid masses in the greater omentum with scattered calcifications. The lesions were similar in attenuation to skeletal muscle on unenhanced images and showed mild progressive enhancement after contrast administration. Magnetic resonance imaging demonstrated low signal intensity on both T1-weighted and T2-weighted images with a similar gradual enhancement pattern. Ultrasound and contrast-enhanced ultrasound showed hypoechoic lesions with limited enhancement. Because malignancy could not be excluded radiologically, surgical resection was performed. Histopathological examination demonstrated spindle cell proliferation within dense hyalinized collagenous stroma with focal chronic inflammatory infiltrates. Immunohistochemical findings supported the diagnosis of reactive nodular fibrous pseudotumor. The patient recovered well after surgery and remained recurrence-free during more than 4 years of follow-up. This case indicates that reactive nodular fibrous pseudotumor should be included in the differential diagnosis of solid omental masses, even in patients without a history of abdominal surgery or inflammation. Multimodality imaging may provide important clues to its fibrous nature, but definitive diagnosis still depends on histopathological confirmation. Greater awareness of this rare entity may reduce misdiagnosis and help avoid unnecessary aggressive treatment.

Dexmedetomidine (DEX) seems to hold a potential neuroprotective role, possibly mediated by the attenuation of oxidative stress and neuroinflammation. This study aimed to delineate the effect of DEX used as an adjunct anaesthetic on cerebral oxygenation, cerebral injury and the release of inflammatory markers in brain tumour surgery. Fifty-six patients undergoing craniotomy for brain tumour excision were randomly assigned to receive either DEX (1&#x2009;&#x3bc;g/kg for 10&#xa0;min and thereafter 0.7&#xa0;&#x3bc;g/kg/h) or placebo. Arterial and jugular-bulb blood samples were collected at predefined time-points, whereas a concomitant hemodynamic profile was obtained intraoperatively. S100B protein, neuron-specific enolase (NSE), tumour necrosis factor-&#x3b1; (TNF-&#x3b1;), interleukin-6 (IL-6) and cortisol levels were determined at baseline and 6 and 24&#x2009;h postoperatively. Demographic and perioperative characteristics were comparable between groups. Propofol consumption was considerably reduced in DEX-treated patients (p&#x2009;<&#x2009;0.001). Measured (jugular-bulb oxygen saturation and partial pressure of oxygen) and estimated (oxygen and carbon dioxide arterial-jugular differences, brain oxygen extraction ratio) cerebral oxygenation indices were favourably affected by DEX infusion (p&#x2009;<&#x2009;0.05), yet this effect was valid for 15&#x2009;min (p&#x2009;<&#x2009;0.05), corresponding to transient systemic hemodynamic augmentation. Moreover, postoperative S100B, NSE, TNF-&#x3b1;, IL-6 and cortisol levels were significantly attenuated in the DEX group (p&#x2009;<&#x2009;0.01). DEX may attenuate the release of cerebral injury and neuroinflammation biomarkers and transiently improve hemodynamics and cerebral oxygenation during brain tumour surgery. Nonetheless, these surrogate effects do not establish clinically relevant neuroprotection, and potential dose-related hemodynamic instability warrants cautious, individualized use.

Oxytocin (OXT), a neuropeptide produced in the paraventricular nucleus (PVN) of the hypothalamus, regulates social behaviour, stress responses, and memory. Our previous studies demonstrated that intracerebroventricular administration of OXT ameliorates amyloid-&#x3b2;-induced cognitive deficits and that selective activation of PVN OXT neurons enhances memory performance. These findings suggest that endogenous OXT secretion is essential for normal memory processing and that its impairment may lead to cognitive dysfunction. To test this hypothesis, we generated oxytocin neuron-specific conditional knockout (cKO) mice for the Ca2+-dependent activator protein for secretion 2 (CAPS2) by crossing Caps2-floxed mice with oxytocin-iCre mice. In these mice, OXT exocytosis was selectively impaired in OXT neurons. Behavioural analyses revealed that Caps2 cKO mice exhibited deficits in long-term memory in the novel object recognition test (NORT) and passive avoidance tests, whereas short-term spatial memory assessed by the Y-maze test remained unaffected. Electrophysiological recordings further showed that hippocampal long-term potentiation was markedly attenuated in Caps2 cKO mice. Consistently, phosphorylated ERK levels in the ventral hippocampus were significantly reduced following the NORT. These findings demonstrate that CAPS2-dependent OXT release is critical for long-term memory formation and hippocampal synaptic plasticity. Our results provide new insight into the physiological role of endogenous OXT signalling in cognitive function and suggest its potential relevance to the pathogenesis of memory disorders such as Alzheimer's disease.

Bovine tuberculosis&#xa0;(bTB), caused by Mycobacterium bovis, is a zoonosis that threatens public health and causes substantial economic losses in livestock. The suboptimal Escherichia coli-expressed recombinant proteins limit the diagnostic performance of current bTB&#xa0;serological tests. To overcome this limitation, we evaluated Mycolicibacterium smegmatis as an expression host capable of producing recombinant antigens with post-translational modifications comparable to those of M. bovis. Ten antigen candidates were individually expressed in E. coli using the pET-26b(&#x2009;+) vector and in M. smegmatis using the pSO&#x394;Bam vector. Their diagnostic performance was evaluated using an&#xa0;enzyme-linked immunosorbent assay&#xa0;(ELISA) with plasma samples from interferon-gamma release assay (IGRA)-negative (n&#x2009;=&#x2009;30) and -positive (n&#x2009;=&#x2009;46) cattle in South Korea, followed by receiver operating characteristic (ROC) curve analysis. Among the single antigens, LprA expressed in M. smegmatis demonstrated diagnostic performance comparable to that of&#xa0;the well-established antigen MPB70 (sensitivity: 50.0%, specificity: 96.6%, AUC: 0.791). In addition, several M. smegmatis-derived antigens showed higher concordance with the IGRA results, as assessed by Cohen's kappa and Fisher's exact tests, and a stronger association between age and antigen-specific antibody responses was observed among IGRA-positive cattle. Moreover, a multiple logistic regression model incorporating eight antigens, including those derived from both hosts, achieved high predictive accuracy for IGRA results (sensitivity: 87.0%, specificity: 100%, AUC: 0.991). These findings suggest that M. smegmatis is a promising host for identifying novel antigens and that a multi-host strategy may improve bTB serodiagnosis.

Alterations in plasma sphingomyelin (SM) levels have been reported in Alzheimer's disease (AD), pointing to disturbances in lipid metabolism that may contribute to disease pathogenesis. Neuronal damage in early AD triggers tau release into central and peripheral systems. Despite influence from peripheral contributions, alterations in plasma total-tau (T-tau) remain valuable in indicating AD-related neurodegeneration. Investigating relationships between SM metabolism and tau release during preclinical AD may uncover important biochemical processes and support advancing early non-invasive detection and treatment approaches. This cross-sectional study investigated cognitively unimpaired (CU) older adults from the KARVIAH cohort, grouped by cortical amyloid-&#x3b2; (A&#x3b2;) status through positron emission tomography (PET) imaging (CU A&#x3b2;- and CU A&#x3b2;+) and utilised a Biocrates-targeted metabolomic platform and Single-molecule array (Simoa) technology to quantify plasma levels of SMs and T-tau, respectively. Associations between circulating SMs and T-tau were examined within each group, with T-tau-associated SMs further evaluated for their association with cognitive performance and cortical A&#x3b2; burden and their potential to discriminate CU A&#x3b2;+ from CU A&#x3b2;- individuals. Significant positive correlations were observed between SMs and T-tau levels exclusively in CU A&#x3b2;+ individuals, suggesting connections between SM-mediated biochemical pathways and tau release from early neurodegeneration in preclinical AD. Lower SM levels were associated with weaker working memory and executive function, as well as poorer global cognition, indicating their potential predictive value for weaker cognitive performance. Moreover, SMs were also inversely associated with cortical A&#x3b2; load in CU A&#x3b2;+ individuals, possibly reflecting early SM-mediated neuroprotective responses against AD pathogenesis. Receiver operating characteristic analysis further revealed the significant potential of the SM panel in distinguishing cortical PET-A&#x3b2; status and enhancing the predictive performance of plasma T-tau in CU individuals. Therefore, circulating T-tau-associated SMs may serve as promising early biomarkers of lipid-mediated processes in CU older adults with cortical amyloid pathology and tau-related neurodegeneration.

Low-level laser therapy (LLLT) is being increasingly applied in regenerative medicine due to its ability to modulate cellular metabolism and support repair processes. However, the effect of various exposure parameters on fibroblast activity still does not remain fully understood. The study aim was to evaluate the effect of selected LLLT parameters (808&#xa0;nm, 100 and 200 mW, 2 and 10&#xa0;J/cm&#xb2;, pulsed beam) on the biological activity of fibroblasts in vitro. Fibroblasts were exposed to the established exposure parameters, and then the number of adherent and metabolically active cells, their migration, adenylate kinase (AK) as well as nitric oxide (NO) levels, cytokine secretion, metalloproteinase (MMP-2, MMP-9) activity, and oxidative-antioxidant potential were assessed. The most favourable effects were achieved with 200 mW; 2&#xa0;J/cm&#xb2; and 100&#xa0;m; 10&#xa0;J/cm&#xb2; exposure parameters. In these conditions, increased number of adherent and metabolically active cells, and elevated migration were observed. Moreover, in this condition decreased AK release and NO secretion were found. Furthermore, LLLT reduced in fibroblasts interleukin 6 (IL-6) and interleukin 8 (IL-8) secretion as well as affected the activity of metalloproteinases, what corresponded with subsequent wound healing process. Additionally, a beneficial effect on maintaining the oxidative-antioxidant balance in fibroblasts was noted. In summary, the effects of LLLT on fibroblasts depend on the applied irradiation parameters, and appropriately selected LLLT treatment (200 mW; 2&#xa0;J/cm&#xb2; and 100 mW; 10&#xa0;J/cm&#xb2;,) stabilise fibroblast metabolism, limits their proinflammatory response and promotes extracellular matrix remodelling (ECM). These results confirm the potential of LLLT as an effective method supporting regenerative processes in the treatment of tissue damage.