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22 pages, 2004 KB  
Review
Exercise, Cellular Senescence, and Cancer: Novel Perspectives on Functional Aging Through Block Strength Training in Older Adults—A Narrative Review
by Rodrigo L. Castillo, Emilio Jofré-Saldía, Daniela Cáceres-Vergara, Georgina M. Renard and Esteban G. Figueroa
Biomedicines 2026, 14(4), 875; https://doi.org/10.3390/biomedicines14040875 (registering DOI) - 11 Apr 2026
Abstract
Population aging has markedly increased the burden of cancer in older adults, in whom frailty, sarcopenia, and reduced physiological reserve limit tolerance to treatment and worsen clinical outcomes. Aging is accompanied by progressive functional decline and by biological processes such as cellular senescence, [...] Read more.
Population aging has markedly increased the burden of cancer in older adults, in whom frailty, sarcopenia, and reduced physiological reserve limit tolerance to treatment and worsen clinical outcomes. Aging is accompanied by progressive functional decline and by biological processes such as cellular senescence, characterized by irreversible cell cycle arrest, chronic low-grade inflammation, and impaired immune surveillance. The accumulation of senescent cells and the persistence of a senescence-associated secretory phenotype contribute to tissue dysfunction and generate a microenvironment that favors tumor initiation and progression. Physical exercise has been associated with attenuation of inflammation, improvements in metabolic and immune function, and with lower levels of senescence-related biomarkers. Although aerobic exercise has been extensively studied in this setting, resistance training holds relevance for older adults due to its capacity to counteract sarcopenia, preserve muscle strength and power, and sustain functional independence. Structured and periodized approaches to resistance exercise may further enhance these benefits by delivering targeted stimuli aligned with age-related physiological deficits. Block strength training (BST), a periodized model that concentrates training adaptations into sequential phases of maximal strength, power, and muscular endurance, has demonstrated consistent improvements in functional performance and reductions in frailty risk in community-dwelling older adults. BST improves physical function. It may also influence biological processes related to aging and cancer; however, mechanistic evidence specific to BST remains to be established. We hypothesized that the exercise in block as a targeted, a structured and physiologically grounded resistance training intervention highlights the potential of BST to promote functional aging and healthy. In the case of cancer biology, and the environment near to tumour, the relationship between aging mechanisms in older adults and controlled exercise effects are currently in advance, but mechanistic trials are still lacking. Finally, we propose a novel training method, structured and personalized, that could impact different clinical outcomes in older patients with cancer. Full article
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19 pages, 1177 KB  
Review
Imaging Engineering and Artificial Intelligence in Urinary Stone Disease: Low-Dose Computed Tomography, Spectral Technologies, and Predictive Models
by Shota Iijima, Takanobu Utsumi, Rino Ikeda, Naoki Ishitsuka, Takahide Noro, Yuta Suzuki, Yuka Sugizaki, Takatoshi Somoto, Ryo Oka, Takumi Endo, Naoto Kamiya and Hiroyoshi Suzuki
Eng 2026, 7(4), 174; https://doi.org/10.3390/eng7040174 (registering DOI) - 11 Apr 2026
Abstract
Urinary stone disease is common, recurrent, and increasingly managed through imaging-driven pathways, yet standard-dose CT of the kidneys, ureters, and bladder (CT KUB) raises concerns about cumulative radiation exposure and the limited use of quantitative imaging information for risk stratification. This review synthesizes [...] Read more.
Urinary stone disease is common, recurrent, and increasingly managed through imaging-driven pathways, yet standard-dose CT of the kidneys, ureters, and bladder (CT KUB) raises concerns about cumulative radiation exposure and the limited use of quantitative imaging information for risk stratification. This review synthesizes contemporary evidence on dose-optimized CT, advanced spectral technologies, and artificial intelligence (AI)-enabled analytics that are reshaping diagnosis, treatment selection, and triage. This review summarizes data supporting low-dose and ultra-low-dose CT protocols that preserve diagnostic accuracy while substantially reducing dose, and discusses how dual-energy CT, photon-counting CT, and radiomics facilitate noninvasive stone characterization and extraction of imaging biomarkers beyond size and location. It also reviews AI approaches for automated detection, segmentation, and volumetric quantification across CT, KUB, and ultrasounds, highlighting their potential to standardize stone-burden metrics. It further examines predictive models, including logistic regression, nomograms, and machine learning, for perioperative infectious complications, emergency department admission or intervention, procedure success, and long-term recurrence, and outlines reporting and validation frameworks and implementation considerations, including software as a medical device regulation and human oversight. In contrast to prior reviews that consider imaging and AI separately, this review integrates dose reduction, spectral characterization, and AI-driven analytics within real-world clinical pathways to distinguish established clinical applications from those that remain investigational. Integrating advanced CT and AI outputs into well-validated prediction models embedded in real-world workflows may enable safer imaging, more consistent triage, and more personalized follow-up for urinary stone disease. Full article
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30 pages, 8598 KB  
Article
Synergistic Virus Neutralizing Activities of European Black Elderberry Fruit Extract and Iota-Carrageenan Against SARS-CoV-2, Influenza A Virus and Respiratory Syncytial Virus
by Christian Setz, Melanie Setz, Pia Rauch, Oskar Schleicher, Stephan Plattner, Andreas Grassauer and Ulrich Schubert
Nutrients 2026, 18(8), 1205; https://doi.org/10.3390/nu18081205 - 10 Apr 2026
Abstract
Background/Objectives: Seasonal waves of respiratory viruses—including SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV)—continue to pose a global health burden and highlight the need for antiviral agents that are effective, safe, broadly active, affordable, and widely accessible. Current interventions are limited [...] Read more.
Background/Objectives: Seasonal waves of respiratory viruses—including SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV)—continue to pose a global health burden and highlight the need for antiviral agents that are effective, safe, broadly active, affordable, and widely accessible. Current interventions are limited by the need for their early administration, the risk of resistance, their costs, and the restricted availability in large parts of the world. For certain natural products, such as European black elderberry (Sambucus nigra L.) fruit extract (ElderCraft®; EC) and the seaweed-derived sulfated polymer iota-carrageenan (IC), antiviral activities against respiratory viruses, particularly IAV and SARS-CoV-2, have previously been shown. Here, we assessed the antiviral activity of IC and an anthocyanin-standardized EC extract against SARS-CoV-2, IAV, and RSV, either as monotherapy or in multiple-dose combinations. Methods: MDCKII cells were infected with IAVPR8, human Calu-3 lung epithelial cells with the SARS-CoV-2 Omicron variant, and HEp-2 cells with RSV (A2 strain). Inhibitors were administered either by pre-incubation of cell-free virions prior to infection or, in separate time-of-addition experiments, during or post-infection. Viral replication was quantified by qRT-PCR or intracellular immunostaining. Cytotoxicity was evaluated using a neutral red uptake assay. Results: Most intriguingly, both EC and IC are able to neutralize virions derived from SARS-CoV-2, IAV, or RSV extracellularly in a dose-dependent manner. Notably, EC and IC alone exhibited strong anti-RSV activity, which was not reported previously. Most importantly, combined treatment with IC and EC caused a pronounced synergistic antiviral effect against the tested viruses, as confirmed by the Bliss independence model, without any detectable impact on cell viability. Finally, solutions prepared from matrix-standardized mono- or combi-lozenges, containing IC and/or EC in high or low doses, reproduced the antiviral and synergistic combination effects observed with the pure compounds. Conclusions: In summary, these findings support further development of EC and IC as a topically accessible, virion-neutralizing combination (e.g., lozenges) to provide additional protection against major respiratory viruses and potentially strengthen pandemic preparedness. Full article
(This article belongs to the Section Phytochemicals and Human Health)
29 pages, 4477 KB  
Article
The Effectiveness of an Augmented Reality-Based Early Intervention Program Using Interactive Games to Enhance Eye Contact as a Nonverbal Communication Skill in Children with Autism: A Single-Case Experimental Design
by Shoeb Saleh and Rommel AlAli
J. Intell. 2026, 14(4), 64; https://doi.org/10.3390/jintelligence14040064 - 10 Apr 2026
Abstract
Children with Autism Spectrum Disorder (ASD) frequently exhibit marked impairments in nonverbal communication, particularly in eye contact, which serves as a foundational element for social interaction and relational development. This study evaluated the effectiveness of an early intervention program utilizing interactive games supported [...] Read more.
Children with Autism Spectrum Disorder (ASD) frequently exhibit marked impairments in nonverbal communication, particularly in eye contact, which serves as a foundational element for social interaction and relational development. This study evaluated the effectiveness of an early intervention program utilizing interactive games supported by Augmented Reality (AR) technology to enhance eye contact behaviors, specifically initiation and maintenance, in children with autism. Using a multiple baseline across participants single-case experimental design, four boys (aged 5–7 years) diagnosed with ASD participated in an 8-week intervention at a specialized center in Saudi Arabia. The intervention featured tablet-based, gamified AR tasks incorporating real-time visual feedback, graduated difficulty levels, and reinforcement mechanisms designed to elicit social gaze and sustained eye contact. Eye contact duration and frequency were measured during structured social interactions via systematic direct observation. The results demonstrated significant improvements across all participants, with the mean duration of eye contact increasing from a baseline of 2.0 s to 5.8 s post-intervention. Visual analysis revealed robust treatment effects, further supported by substantial Tau-U effect sizes (range = 0.89–0.96; M = 0.93). Follow-up data collected three weeks post-intervention confirmed the maintenance of gains for three of the four participants. These findings suggest that AR-based interventions provide an effective and culturally responsive approach for enhancing specific nonverbal communication behaviors among children with autism in Middle Eastern contexts. Implications for clinical practice and directions for future research are discussed. Full article
16 pages, 832 KB  
Article
Clinical Practice Patterns in the Physiotherapy Management of Tension-Type Headache Among Spanish Physiotherapists
by Ana Bravo-Vazquez, Elena De-La-Barrera-Aranda, Ernesto Anarte-Lazo, Cleofas Rodriguez-Blanco and Carlos Bernal-Utrera
J. Clin. Med. 2026, 15(8), 2896; https://doi.org/10.3390/jcm15082896 - 10 Apr 2026
Abstract
Background: Tension-type headache (TTH) is the most prevalent primary headache disorder worldwide and represents a major source of disability related to chronic pain. Despite its high prevalence, uncertainty remains regarding optimal conservative management strategies, and limited evidence is available on how physiotherapists [...] Read more.
Background: Tension-type headache (TTH) is the most prevalent primary headache disorder worldwide and represents a major source of disability related to chronic pain. Despite its high prevalence, uncertainty remains regarding optimal conservative management strategies, and limited evidence is available on how physiotherapists apply existing recommendations in routine clinical practice. Objective: The objective was to explore physiotherapists’ perceptions, clinical experiences, and treatment strategies in the management of tension-type headache, with particular emphasis on commonly used interventions, clinical decision-making, and characteristics of physiotherapy care. Methods: A cross-sectional survey study was conducted using a self-administered online survey developed in accordance with the CHERRIES guidelines. One hundred Spanish physiotherapists with clinical experience in treating patients with TTH participated. Quantitative data were analyzed descriptively, while open-ended responses were examined using inductive thematic analysis following the framework proposed by Braun and Clarke. Results: Manual therapy was the most frequently reported intervention (96%), followed by therapeutic exercise (61%) and invasive techniques, primarily dry needling (48%). The suboccipital and upper cervical regions were consistently identified as primary therapeutic targets, reflecting a predominant craniocervical treatment focus. Most respondents reported individualized treatment plans, typically delivered in weekly sessions lasting 45–60 min, with expected clinical improvement within 4–6 weeks. Pain education strategies were reported infrequently. Considerable variability was observed in the selection and combination of therapeutic techniques. Conclusions: Physiotherapists managing tension-type headache commonly adopt a multimodal approach, largely centered on manual and tissue-focused interventions. Although many reported practices are aligned with current evidence, the substantial heterogeneity observed and the limited integration of biopsychosocial strategies highlight the need for consensus-based guidelines and further research addressing real-world clinical effectiveness. Full article
(This article belongs to the Special Issue Headache: Updates on the Assessment, Diagnosis and Treatment)
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19 pages, 318 KB  
Perspective
Extending the Reach of Interventions to Treat Mental Disorders
by Alan E. Kazdin
Psychiatry Int. 2026, 7(2), 78; https://doi.org/10.3390/psychiatryint7020078 - 10 Apr 2026
Abstract
The majority of people with mental disorders in low-, middle-, and high-income countries do not receive any intervention for their symptoms, despite enormous advances in developing evidence-based psychosocial treatments and medications. The perspective and viewpoint article discusses and illustrates digital and technology-based interventions [...] Read more.
The majority of people with mental disorders in low-, middle-, and high-income countries do not receive any intervention for their symptoms, despite enormous advances in developing evidence-based psychosocial treatments and medications. The perspective and viewpoint article discusses and illustrates digital and technology-based interventions and activities in everyday life that have been shown to reduce symptoms of mental disorders. The article begins with background on the treatment gap and a discussion of why treatments do not reach people in need. Digital and technology-based interventions and everyday activities are presented to complement current treatments with the goal of scaling interventions to serve more people in need and to circumvent many of the usual barriers that preclude people from seeking or receiving traditional mental health services. Interventions in each of the categories are illustrated. The challenge is to integrate such interventions in mental health practices, to better promote these at the population level, and to monitor their impact. Full article
11 pages, 219 KB  
Article
Impact of Levothyroxine Treatment for Hypothyroidism on the Risk of Psychiatric Interventions in Children and Adolescents with Anxiety Disorders: A Retrospective Analysis of Data from the TriNetX Platform
by Marta Hilmon, Janina Kulińska, Dominik Krzyżanowski and Katarzyna Skórkowska-Telichowska
J. Clin. Med. 2026, 15(8), 2893; https://doi.org/10.3390/jcm15082893 - 10 Apr 2026
Abstract
Background/Objectives: Hypothyroidism, including subclinical hypothyroidism, may affect mental health in children and adolescents through disturbances of neurotransmission and dysregulation of the hypothalamic–pituitary–thyroid and stress axes. Anxiety disorders are common in this population and frequently coexist with somatic symptoms overlapping those of hypothyroidism, [...] Read more.
Background/Objectives: Hypothyroidism, including subclinical hypothyroidism, may affect mental health in children and adolescents through disturbances of neurotransmission and dysregulation of the hypothalamic–pituitary–thyroid and stress axes. Anxiety disorders are common in this population and frequently coexist with somatic symptoms overlapping those of hypothyroidism, complicating diagnosis and treatment. This study aimed to evaluate the association between levothyroxine treatment for hypothyroidism and the need for psychiatric interventions in children and adolescents with anxiety disorders. Methods: A retrospective cohort study was performed using data from the TriNetX global research network. Patients aged 5–18 years with diagnoses of hypothyroidism (ICD-10: E03) and anxiety disorders (ICD-10: F41) were included. Two propensity score–matched cohorts were analysed: patients treated with levothyroxine (n = 1861) and untreated patients (n = 1861). Outcomes included psychiatric hospitalisations, use of selective serotonin reuptake inhibitors and tricyclic-like antidepressants, frequency of psychiatric and psychotherapeutic consultations, and the occurrence of suicidal ideation and self-harm. Results: Levothyroxine treatment was associated with lower odds of SSRI use (OR = 0.58; p < 0.001), fewer psychiatric consultations (OR = 0.48; p < 0.001), and lower recorded use of psychotherapy (OR = 0.75; p = 0.029). Suicidal ideation and self-harm were recorded less frequently in the treated group (OR = 0.53; p = 0.001). No significant differences were observed in psychiatric hospitalisation rates. Use of tricyclic-like antidepressants was uncommon and did not differ significantly between groups. Conclusions: Among children and adolescents with comorbid anxiety disorders, levothyroxine treatment for hypothyroidism is associated with lower recorded utilization of certain psychiatric services and lower recorded rates of suicidal ideation and self-harm. Due to the retrospective design, causal inferences cannot be made, and the findings should be considered hypothesis-generating, requiring confirmation in prospective studies with standardised psychiatric outcome measures. Full article
(This article belongs to the Section Mental Health)
16 pages, 418 KB  
Review
Lifestyle Medicine Perspectives from Nursing in Community Care Setting: A Narrative Review
by Francesco Sacchini, Francesco Scerbo, Karolina Kowalcze, Paola Pantanetti, Sophia Russotto, Otilia Enache, Stefano Mancin, Cuc Thi Thu Nguyen, Diego Lopane, Francesca Marfella, Gabriele Caggianelli, Robert Krysiak, Fabio Petrelli and Giovanni Cangelosi
Nurs. Rep. 2026, 16(4), 128; https://doi.org/10.3390/nursrep16040128 - 10 Apr 2026
Abstract
Background/Objectives: Chronic diseases pose a major challenge for healthcare systems, requiring integrated, patient-centered approaches that combine clinical management, prevention, and self-care. Lifestyle Medicine (LM) and lifestyle in general offers complementary frameworks to address these needs. However, the potential integration of LM within [...] Read more.
Background/Objectives: Chronic diseases pose a major challenge for healthcare systems, requiring integrated, patient-centered approaches that combine clinical management, prevention, and self-care. Lifestyle Medicine (LM) and lifestyle in general offers complementary frameworks to address these needs. However, the potential integration of LM within community nursing—particularly through the role of Family and Community Nurse (FCN)—has not been comprehensively synthesized. This narrative review aimed to synthesize international evidence on the role of community nursing—particularly FCN—in integrating chronic care management and LM view. Methods: For quality assessment, a narrative review was conducted in accordance with the SANRA criteria to enable the integration of heterogeneous evidence and a comprehensive synthesis of this complex topic. Literature searches were performed in the PubMed–Medline database, and the final screening of references from included studies was used to identify relevant manuscripts. Primary studies published in English over the past ten years were screened and analyzed using the PICOS framework. Sixteen eligible studies were included in the final synthesis. Results: The included studies indicated that nurse-led community interventions in LM view were associated with improvements in self-management, treatment adherence, and selected clinical outcomes, such as blood pressure, glycated hemoglobin, and physical activity levels. Empowerment-based approaches and the use of digital or telehealth tools supported patient engagement and health literacy. At the organizational level, multidisciplinary collaboration, shared protocols, and professional leadership emerged as key factors in sustaining continuity and quality of care, while organizational fragmentation and limited training in behavioral counseling were commonly reported barriers. Conclusions: Community nursing, particularly through FCNs, plays a relevant role in integrating chronic care management and LM approaches, contributing to improved self-management, treatment adherence, and selected clinical outcomes. The evidence highlights the importance of empowerment-based interventions, digital support tools, and multidisciplinary collaboration in enhancing care continuity and patient engagement. Addressing organizational barriers and strengthening behavioral counseling training remain essential to support effective implementation in community settings. Full article
11 pages, 989 KB  
Article
Has the Step-Up Approach Improved Prognosis in Severe Necrotizing Acute Pancreatitis?
by Ricardo Gadea-Mateo, Marina Garcés-Albir, Dimitri Dorcaratto, Georgy Kadzhaya-Khlystov, Vicente Sanchiz, Elena Muñoz-Forner, Rosana Villagrasa, Isabel Mora-Oliver, Elisabetta Casula, Mar Juan-Diaz, Pablo Navarro-Cortés, Jorge Guijarro-Rosaleny, Isabel Pascual-Moreno and Luis Sabater
J. Clin. Med. 2026, 15(8), 2881; https://doi.org/10.3390/jcm15082881 - 10 Apr 2026
Abstract
Background/Objectives: Acute pancreatitis is a prevalent pathology with increasing incidence. Despite advances in treatment, some patients still present a severe clinical course with high morbidity and mortality rates. We evaluated the association between implementation of a step-up-based management strategy and clinical outcomes [...] Read more.
Background/Objectives: Acute pancreatitis is a prevalent pathology with increasing incidence. Despite advances in treatment, some patients still present a severe clinical course with high morbidity and mortality rates. We evaluated the association between implementation of a step-up-based management strategy and clinical outcomes in patients with severe acute pancreatitis (SAP) treated at a tertiary referral center. Method: A retrospective observational study was conducted, including patients treated for SAP at a tertiary care center. Clinical outcomes, including mortality, morbidity, and length of hospital stay, were compared between two periods: Period A (1998–2010, classical treatment) and Period B (2011–2021, step-up approach). A subanalysis on minimally invasive techniques was also performed for Period B. Results: In total, 116 patients were included (39 Period A; 77 Period B). Pancreatic fistulas were reduced in Period B (15.38% vs. 5.33%; p = 0.088), as was mortality (30.76% vs. 18.67%; p = 0.15). Open surgeries decreased significantly in Period B (71.9% vs. 16.9%; p = 0.043), as did the mean hospital stay (60.5 ± 28 vs. 33.08 ± 28 days; p < 0.001). When comparing endoscopy management versus Video-Assisted Retroperitoneal Debridement (VARD), the rate of pancreatic fistulas was higher in the VARD group (0% vs. 57.1%; p < 0.01). Patients requiring VARD presented with larger collections (710 cc vs. 1737.9 cc; p = 0.03) and fewer procedures (4.2 ± 2.3 vs. 1.5 ± 0.5; p = 0.002). Conclusions: The step-up management in patients with SAP was associated with a decrease in open surgical approches and length of stay. VARD was performed in patients with higher volume collections and was associated with fewer interventions than patients treated by endoscopic necrosectomy; however, the incidence of pancreatic fistulas was higher. Full article
(This article belongs to the Section General Surgery)
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20 pages, 743 KB  
Review
Patellar Maltracking in Total Knee Arthroplasty: Mechanisms, Prevention and Treatment
by Michał Krupa, Joachim Pachucki, Iga Wiak, Rafał Zabłoński, Paweł Kasprzak, Łukasz Pulik and Paweł Łęgosz
Prosthesis 2026, 8(4), 38; https://doi.org/10.3390/prosthesis8040038 - 10 Apr 2026
Abstract
Patellar maltracking is among the most common causes of anterior knee pain after total knee arthroplasty (TKA), underscoring the need for accurate prevention and treatment. Therefore, the purpose of this narrative review is to provide a comprehensive overview of current evidence on post-TKA [...] Read more.
Patellar maltracking is among the most common causes of anterior knee pain after total knee arthroplasty (TKA), underscoring the need for accurate prevention and treatment. Therefore, the purpose of this narrative review is to provide a comprehensive overview of current evidence on post-TKA tracking, focusing on component alignment, preoperative patient assessment, and revision treatment options. A PubMed database search was performed, leveraging the literature from the last 20 years, and the results were qualitatively synthesized. According to current studies, several precautions should be taken to prevent patellofemoral stress and, consequently, patellar maltracking, such as avoiding internal rotation, valgus alignment, and excessive flexion of the femoral component and internal rotation of the tibial component. Regarding alignment strategies, kinematic alignment appears to offer potential benefits over mechanical alignment in certain functional outcomes and patient satisfaction scores. However, these differences should be interpreted cautiously as they may not always exceed the minimal clinically important difference. Furthermore, recent evidence indicates that quadriceps biomechanics influence TKA outcomes, potentially suggesting that conventional surgical approaches may need to be individualized, though these preliminary findings require prospective validation. Currently, robotic-assisted surgery represents a developmental direction for patient-tailored interventions and offers great promise for better prosthesis customization to the individual patient. Integration of imaging data with dynamic soft-tissue assessment enables more predictable reconstruction of joint kinematics. Regarding surgical treatment, the selection of specific methods requires a prior clinical and radiographic assessment. Indications range from patellar maltracking direction and component malrotation to patient preferences and rehabilitation potential. Ultimately, the future of TKA relies on personalized interventions to prevent complications and improve patient outcomes. This evolution is driven by the shift from mechanical alignment to kinematic alignment, alongside quadriceps tendon assessment and intraoperative robotic-assisted measurement, all aimed at optimizing the accuracy of implant positioning. Full article
(This article belongs to the Section Orthopedics and Rehabilitation)
19 pages, 3249 KB  
Article
Young Human-Derived Microbiota Ameliorates Cognitive Decline and Reproductive Senescence in Aged Mice
by Xiaoying Zhang, Fang Chen, Yinghua Luo, Daotong Li, Junfu Ji, Lingjun Ma, Chen Ma and Xiaosong Hu
Nutrients 2026, 18(8), 1193; https://doi.org/10.3390/nu18081193 - 10 Apr 2026
Abstract
Background/Objectives: Age-related gut microbiota dysbiosis leads to systemic oxidative stress, chronic inflammation, and multi-organ functional decline. However, there is limited evidence supporting microbiota-based therapies for aging. This study aimed to examine the effect of gut microbiota from young donors, particularly those with [...] Read more.
Background/Objectives: Age-related gut microbiota dysbiosis leads to systemic oxidative stress, chronic inflammation, and multi-organ functional decline. However, there is limited evidence supporting microbiota-based therapies for aging. This study aimed to examine the effect of gut microbiota from young donors, particularly those with increasing Bifidobacteria levels through dietary intervention, on age-related declines in fertility, cognition, and reproduction. Methods: We conducted experiments using gut microbiota from young human donors, with or without pre-conditioning with barley leaves (BL), to transplant into aged male mice. Hippocampal metabolome and behavioral assessments were used to identify differences in recognitive regulation during aging. Moreover, testis tissue, semen quality, and offspring studies were determined to investigate the beneficial effects on fertility and underlying mechanism. Conclusions: This preliminary dietary treatment promotes the growth of Bifidobacterium in aged recipient mice. Aged male mice received young fecal microbiota transplants (yFMTs), BL-conditioned yFMTs (BLyFMTs), and a combined treatment of BLyFMT plus recipient BL supplementation. The combined approach significantly increased intestinal Bifidobacterium levels and effectively restored hippocampal metabolomic profiles and cognitive behavior. Additionally, yFMT-based treatments mitigated structural damage to the seminiferous tubules and prevented the germ cell depletion. Consistently, those interventions improved sperm quality and mechanistically enhanced hypothalamic–pituitary–gonadal (HPG) axis activity in aged recipients. These findings highlight Bifidobacterium as a key factor in microbiome-driven rejuvenation, enhancing the effectiveness of yFMTs in addressing aging-related declines. Full article
(This article belongs to the Section Geriatric Nutrition)
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25 pages, 2684 KB  
Review
Gut Microbiota Biomarkers in Patients with Hepatocellular Carcinoma in the Era of Immune Checkpoint Inhibitors
by Maria Cerreto, Marta Maestri, Maria Pallozzi, Lucia Cerrito, Leonardo Stella, Gianluca Ianiro, Antonio Gasbarrini and Francesca Romana Ponziani
Life 2026, 16(4), 641; https://doi.org/10.3390/life16040641 - 10 Apr 2026
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape for hepatocellular carcinoma (HCC); however, a considerable proportion of patients do not achieve durable clinical benefits. This highlights the need for reliable predictive biomarkers, which are currently lacking. The accumulated evidence supports a relevant [...] Read more.
Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape for hepatocellular carcinoma (HCC); however, a considerable proportion of patients do not achieve durable clinical benefits. This highlights the need for reliable predictive biomarkers, which are currently lacking. The accumulated evidence supports a relevant role of the gut–liver axis in modulating immunotherapy outcomes, and several studies have identified distinct microbial features associated with either responders or non-responders. Responders to immunotherapy frequently present with higher microbial diversity and enrichment of beneficial taxa, whereas the expansion of pro-inflammatory and pathogenic bacteria has been associated with primary resistance and increased treatment-related toxicity in non-responders. However, the available findings remain heterogeneous across cohorts, likely owing to differences in geography, diet, liver disease etiology, treatment regimens, and microbiome analytical methods. Machine-learning models integrating metagenomic and metabolomic data have shown encouraging results in defining microbial signatures associated with treatment outcomes, although variability among cohorts currently limits their clinical applicability and generalizability. Beyond microbial taxonomic composition, microbiota-derived metabolites—such as short-chain fatty acids, bile acids, inosine, and tryptophan catabolites—appear to play a crucial role in shaping the tumor microenvironment and host immune responses, thus representing additional candidate biomarkers, also due to the relative ease of their measurement. Finally, microbiota-targeted interventions are emerging as potential strategies to enhance immunotherapy efficacy. Overall, the gut microbiome and its metabolic activity represent promising tools, albeit still under investigation, for patient stratification and personalized management in HCC treated with ICIs. Therefore, this review aims to summarize and critically discuss the current evidence on gut microbiota-derived biomarkers of response and resistance to ICIs in HCC, with particular focus on microbial composition, microbiota-related metabolites, and emerging microbiome-based therapeutic strategies. This narrative review provides an updated overview of the role of gut microbiota as both a biomarker and a therapeutic target in patients with hepatocellular carcinoma (HCC) receiving immune checkpoint inhibitor (ICI) therapy. Full article
21 pages, 1833 KB  
Article
Synergistic Effects of Subsurface Drainage and Root-Zone Oxygenation on Wheat Yield and Ion Homeostasis in Saline Soils with Shallow Groundwater
by Qi Xu, Wenda Du, Changkun Ma and Quanjiu Wang
Plants 2026, 15(8), 1170; https://doi.org/10.3390/plants15081170 - 10 Apr 2026
Abstract
Shallow groundwater in saline soils creates a self-reinforcing cycle where waterlogging-induced root hypoxia impairs the ATP-dependent sodium exclusion mechanisms that plants rely on for salt tolerance. We conducted a two-year field experiment to test whether subsurface drainage must precede root-zone aeration for oxygen [...] Read more.
Shallow groundwater in saline soils creates a self-reinforcing cycle where waterlogging-induced root hypoxia impairs the ATP-dependent sodium exclusion mechanisms that plants rely on for salt tolerance. We conducted a two-year field experiment to test whether subsurface drainage must precede root-zone aeration for oxygen delivery to be effective. The experimental site was located in Heyang County, Weinan City, on the Guanzhong Plain of Shaanxi Province, north-central China—a major alluvial agricultural region representative of shallow-groundwater-induced salinization. The site had saturated paste electrical conductivity of 6.0 dS m−1 and groundwater depth fluctuating between 0.5 and 1.4 m. A randomized complete block design with 2 × 2 factorial arrangement compared four treatments: control (CK), subsurface drainage only (SD), root-zone aeration only (RA), and both interventions combined (SD + RA). Drainage increased air-filled porosity from 5.8% to 13.5%, crossing the 10.2% threshold (95% CI: 9.1–11.3%) where gas-phase continuity emerges according to segmented regression analysis. Without drainage, aeration achieved only 4.2 mg L−1 dissolved oxygen with high spatial variability (CV 12.5%), while the combined treatment reached 6.8 mg L−1 (CV 6.8%). Root ATP content increased by 89% in SD + RA compared to control, accompanied by 56% lower root Na+ and 185% higher K+/Na+ ratio. These physiological changes correlated with 31% higher grain yield (7580 vs. 5798 kg ha−1). The synergy index of 1.40 (95% CI: 1.28–1.52) indicated that combined effects exceeded the sum of individual treatments by 40%. Methane emissions declined by 62%, and the system achieved a 2.9-year payback period with a benefit–cost ratio of 4.08. These results establish drainage as a physical prerequisite for effective oxygenation, providing a mechanistic explanation for the variable performance of aeration systems reported in previous studies. Full article
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